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For NSCLC, neoadjuvant, adjuvant, or both?
This transcript has been edited for clarity.
Dr. West: Here at ASCO 2023 [American Society of Clinical Oncology] in Chicago, we’ve seen some blockbuster presentations in thoracic oncology. Many of these have brought up some important questions about the clinical implications that we need to discuss further.
At ASCO, as well as in the couple or 3 months preceding ASCO, we’ve gotten more and more data on perioperative approaches. Of course, over the past couple of years, we’ve had some new options of postoperative immunotherapy for a year, say, after chemotherapy or possibly after chemotherapy.
We have also had very influential data, such as the CheckMate 816 trial that gave three cycles of chemotherapy with nivolumab vs. chemotherapy alone to patients with stage IB to IIIA disease, but largely, nearly two thirds, with IIIA disease. That showed a very clear improvement in the pathologic complete response (pCR) rate with nivolumab added to chemotherapy and also a highly significant improvement in event-free survival and a strong trend toward improved overall survival. This is FDA approved and has been increasingly adopted, I would say, maybe with some variability by geography and center, but really a good amount of enthusiasm.
Now, we have a bunch of trials that give chemotherapy with immunotherapy. We’ve got the AEGEAN trial with durvalumab. We have Neotorch with chemotherapy and toripalimab. At ASCO 2023, we had a highly prominent presentation of KEYNOTE-671, giving four cycles of chemotherapy with pembrolizumab vs. chemotherapy and placebo.
Then there’s the built-in postoperative component of a year of immunotherapy as well, in all these trials. The data for KEYNOTE-671 look quite good. Of course, the other trials also were significant. I would say the comparator now is not nothing or chemotherapy alone anymore; it’s really against what is the best current standard of care.
It certainly adds some cost, it adds some risk for toxicity, and it adds a year of a patient coming into the clinic and getting IV infusions all this time to get a treatment that the patient has already had for four cycles in most of these trials.
If your cancer is resistant, is there going to be an incremental benefit to giving more of it? What are your thoughts about the risk and benefit? Going to a patient in your own clinic, how are you going to counsel your patients? Will anything change after the presentation of all these data and how you approach preoperatively?
Dr. Rotow: I agree. In some sense, it’s an embarrassment of riches, right?
Dr. West: Yes.
Dr. Rotow: We have so many positive studies looking at perioperative immunotherapy for our patients. They all show improved outcomes, but of course, they all compare with the old control arm of chemotherapy alone in some form, and this is no longer a useful control in this space. The open question is, do you use neoadjuvant, do you use adjuvant, or do you use both?
My high-level takeaway from these data is that the neoadjuvant component appears to be important. I think the overall trend, comparing across studies, of course, is that outcomes seem to be better with the neoadjuvant component. You also get the advantage of potential downstaging and potential greater ease of surgical resection. We know they have lower morbidity resection and shorter surgeries. You can comment on that. You also get your pathologic response data.
Dr. West: You get the feedback.
Dr. Rotow: Exactly.
Dr. West: The deliverability is also a big issue. You know you can much more reliably deliver your intended treatment by doing neoadjuvant followed by surgery.
Dr. Rotow: Exactly.
Dr. West: We know there’s major drop-off if patients have surgery, and in the recovery room they hear you got it all, and then they need to come back and maybe get chemotherapy and immunotherapy for a year. They’d ask, “What for? I can’t see anything.”
Dr. Rotow: Exactly. I think there are many advantages to that neoadjuvant component. I think all or many of us now have integrated this into our routine practice. Now the question is, do you need the adjuvant element or not on top? That is challenging because no trial has compared adjuvant to nonadjuvant. I think we all advocate for the need for this trial to answer this in a more randomized, prospective fashion. Of course, that doesn’t help our clinic practice tomorrow when we see a patient.
Dr. West: Or for the next 4 years.
Dr. Rotow: Or for the next 4 years – exactly. There’s going to be the open question of who really needs this? In some sense, we may be guided by the path response during the surgery itself. I think there may be those who claim that if you have a pCR, do you really need additional therapy? We don’t know the answer, but it’s tempting to say we know the outcomes in event-free survival are extremely good with a pCR.
Dr. West: Which is only 20% or 25% of patients, so it’s not most.
Dr. Rotow: It’s not most, but it’s better than the 2% or so with chemotherapy alone. That’s real progress, and it’s nice to have that readout. For that 80% without a pCR, what to do? I suspect there will be variation from provider to provider and from patient to patient, depending on tolerability to prior therapy, the patient’s wishes around the goals of care, and the patient’s risk for autoimmune toxicities.
Maybe there’s a patient with underlying autoimmune disease who’s gotten their neoadjuvant therapy and done well. You don’t want to risk that ongoing risk of exposure. Perhaps a patient with no risk factors who desires very aggressive treatment might be interested in more treatment.
In KEYNOTE-671, I was interested in the PD-L1 subgroups. These did trend the way you expect, with better responses in PD-L1 high, but there were also good outcomes and benefit to immunotherapy with the perioperative strategy in PD-L1–negative patients.
Dr. West: That didn’t really exclude anybody.
Dr. Rotow: It didn’t exclude anybody. In CheckMate 816, everyone benefited, but the benefit was less with those PD-L1–negative patients.
Dr. West: True.
Dr. Rotow: Absent further data to guide me or any prospective data here comparing these strategies, I might lean toward a longer course of immunotherapy in that population in hopes of triggering a response. I suspect that there will be variation from clinician to clinician in that space.
Dr. West: This is a setting where I feel like I have equipoise. I really feel that the incremental benefit is pretty small.
Dr. Rotow: Small. I agree.
Dr. West: It’s, frankly, somewhat dubious. On the other hand, you’re in a situation where if you know that three of four patients will experience a relapse and less-than-amazing outcomes, it’s hard to leave something that’s FDA approved and studied and a well-sanctioned option on the table if this patient may have relapse later.
In the end, I feel like I’d like to offer this and discuss it with all my patients. I think it’s a great place for shared decision-making because if a patient hears about that and decides they’re not interested, I’ll be fine with that. I think that’s a very sensible approach, but I don’t want to make it unilaterally. Other patients may say they want every opportunity, and if it comes back, at least I’ll know I did everything we could.
Dr. Rotow: Exactly. I agree with your statement about equipoise. I truly think that this is present here in the situation, and that there’s room for discussion in both directions with patients.
Now, one caveat I’d like to add to all these data is that the data should not apply to patients with some of our classic nonsmoking-associated driver mutations. This is another piece to the neoadjuvant data that I think is worth commenting on – the need to get appropriate testing before initiation of therapy and the pitfalls of starting this kind of treatment without knowing full biomarker testing. I think that’s something we have to watch for in our clinical practice as well.
Dr. West: Perhaps especially if we’re talking about doing a year of postoperative and someone has an ALK rearrangement or an EGFR mutation and we didn’t know it. That is a group where we’re worried about a rapid transition and potentially prohibitive, even life-threatening, toxicities from not planning in advance for this. This is something you don’t want to give concurrently or one right on top of the other. You don’t want to give immunotherapy and then transition right to targeted therapy. It’s dangerous.
Dr. Rotow: Exactly. The stakes were already high with neoadjuvant alone, but at least you had that gap of the presurgical period, surgical recovery, and then initiation of adjuvant therapy, if needed, or at relapse. With a postoperative long adjuvant period, those stakes are elevated because the immunotherapy exposure continues, so it’s something to be mindful of.
Dr. West: We have a general sense that many, but not all, of the targets that we’re talking about are associated with low benefit from immunotherapy. It’s not that well studied. I think this is another place for individualized discussion of the pros and cons. They were included in the trial, but they probably benefit less.
Dr. Rotow: Exactly. I think with the best established, EGFR and ALK probably are not benefiting much. They were actually included in the trial. Many of the neoadjuvant studies do not allow them to enroll if they’re known. On the other end of that spectrum, I think KRAS is just fine to treat with immunotherapy.
Dr. West: Sure.
Dr. Rotow: It’s an actionable driver. It’s not a traditional nonsmoking-associated driver, and those do just fine.
Dr. West: The studies show that these patients benefit just as much, at least, as the other patients.
Dr. Rotow: Exactly. I would never withhold this form of therapy for a KRAS driver mutation. The others, I think, are still in a gray zone. Depending on the patient demographics and tobacco use, I may elicit more or less caution in that space.
Dr. West: Well, I think we’re going to have much to still tease apart, with room for judgment here without a strong sense of the data telling us exactly what to do.
Dr. Rotow: Exactly.
Dr. West: There’s a large amount of excitement and interest in these new data, but there are still many open questions. I hope we continue to mull it over as we get more data and more insight to shape our plans.
Dr. West is an associate professor at City of Hope Comprehensive Cancer Center in Duarte, Calif., and vice president of network strategy at AccessHope in Los Angeles. Dr. Rotow is the clinical director of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute in Boston. Dr. West reported conflicts of interest with Ariad/Takeda, Bristol Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly. Dr. Rotow reported conflicts of interest with Genentech, AstraZeneca,Guardant, and Janssen.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Dr. West: Here at ASCO 2023 [American Society of Clinical Oncology] in Chicago, we’ve seen some blockbuster presentations in thoracic oncology. Many of these have brought up some important questions about the clinical implications that we need to discuss further.
At ASCO, as well as in the couple or 3 months preceding ASCO, we’ve gotten more and more data on perioperative approaches. Of course, over the past couple of years, we’ve had some new options of postoperative immunotherapy for a year, say, after chemotherapy or possibly after chemotherapy.
We have also had very influential data, such as the CheckMate 816 trial that gave three cycles of chemotherapy with nivolumab vs. chemotherapy alone to patients with stage IB to IIIA disease, but largely, nearly two thirds, with IIIA disease. That showed a very clear improvement in the pathologic complete response (pCR) rate with nivolumab added to chemotherapy and also a highly significant improvement in event-free survival and a strong trend toward improved overall survival. This is FDA approved and has been increasingly adopted, I would say, maybe with some variability by geography and center, but really a good amount of enthusiasm.
Now, we have a bunch of trials that give chemotherapy with immunotherapy. We’ve got the AEGEAN trial with durvalumab. We have Neotorch with chemotherapy and toripalimab. At ASCO 2023, we had a highly prominent presentation of KEYNOTE-671, giving four cycles of chemotherapy with pembrolizumab vs. chemotherapy and placebo.
Then there’s the built-in postoperative component of a year of immunotherapy as well, in all these trials. The data for KEYNOTE-671 look quite good. Of course, the other trials also were significant. I would say the comparator now is not nothing or chemotherapy alone anymore; it’s really against what is the best current standard of care.
It certainly adds some cost, it adds some risk for toxicity, and it adds a year of a patient coming into the clinic and getting IV infusions all this time to get a treatment that the patient has already had for four cycles in most of these trials.
If your cancer is resistant, is there going to be an incremental benefit to giving more of it? What are your thoughts about the risk and benefit? Going to a patient in your own clinic, how are you going to counsel your patients? Will anything change after the presentation of all these data and how you approach preoperatively?
Dr. Rotow: I agree. In some sense, it’s an embarrassment of riches, right?
Dr. West: Yes.
Dr. Rotow: We have so many positive studies looking at perioperative immunotherapy for our patients. They all show improved outcomes, but of course, they all compare with the old control arm of chemotherapy alone in some form, and this is no longer a useful control in this space. The open question is, do you use neoadjuvant, do you use adjuvant, or do you use both?
My high-level takeaway from these data is that the neoadjuvant component appears to be important. I think the overall trend, comparing across studies, of course, is that outcomes seem to be better with the neoadjuvant component. You also get the advantage of potential downstaging and potential greater ease of surgical resection. We know they have lower morbidity resection and shorter surgeries. You can comment on that. You also get your pathologic response data.
Dr. West: You get the feedback.
Dr. Rotow: Exactly.
Dr. West: The deliverability is also a big issue. You know you can much more reliably deliver your intended treatment by doing neoadjuvant followed by surgery.
Dr. Rotow: Exactly.
Dr. West: We know there’s major drop-off if patients have surgery, and in the recovery room they hear you got it all, and then they need to come back and maybe get chemotherapy and immunotherapy for a year. They’d ask, “What for? I can’t see anything.”
Dr. Rotow: Exactly. I think there are many advantages to that neoadjuvant component. I think all or many of us now have integrated this into our routine practice. Now the question is, do you need the adjuvant element or not on top? That is challenging because no trial has compared adjuvant to nonadjuvant. I think we all advocate for the need for this trial to answer this in a more randomized, prospective fashion. Of course, that doesn’t help our clinic practice tomorrow when we see a patient.
Dr. West: Or for the next 4 years.
Dr. Rotow: Or for the next 4 years – exactly. There’s going to be the open question of who really needs this? In some sense, we may be guided by the path response during the surgery itself. I think there may be those who claim that if you have a pCR, do you really need additional therapy? We don’t know the answer, but it’s tempting to say we know the outcomes in event-free survival are extremely good with a pCR.
Dr. West: Which is only 20% or 25% of patients, so it’s not most.
Dr. Rotow: It’s not most, but it’s better than the 2% or so with chemotherapy alone. That’s real progress, and it’s nice to have that readout. For that 80% without a pCR, what to do? I suspect there will be variation from provider to provider and from patient to patient, depending on tolerability to prior therapy, the patient’s wishes around the goals of care, and the patient’s risk for autoimmune toxicities.
Maybe there’s a patient with underlying autoimmune disease who’s gotten their neoadjuvant therapy and done well. You don’t want to risk that ongoing risk of exposure. Perhaps a patient with no risk factors who desires very aggressive treatment might be interested in more treatment.
In KEYNOTE-671, I was interested in the PD-L1 subgroups. These did trend the way you expect, with better responses in PD-L1 high, but there were also good outcomes and benefit to immunotherapy with the perioperative strategy in PD-L1–negative patients.
Dr. West: That didn’t really exclude anybody.
Dr. Rotow: It didn’t exclude anybody. In CheckMate 816, everyone benefited, but the benefit was less with those PD-L1–negative patients.
Dr. West: True.
Dr. Rotow: Absent further data to guide me or any prospective data here comparing these strategies, I might lean toward a longer course of immunotherapy in that population in hopes of triggering a response. I suspect that there will be variation from clinician to clinician in that space.
Dr. West: This is a setting where I feel like I have equipoise. I really feel that the incremental benefit is pretty small.
Dr. Rotow: Small. I agree.
Dr. West: It’s, frankly, somewhat dubious. On the other hand, you’re in a situation where if you know that three of four patients will experience a relapse and less-than-amazing outcomes, it’s hard to leave something that’s FDA approved and studied and a well-sanctioned option on the table if this patient may have relapse later.
In the end, I feel like I’d like to offer this and discuss it with all my patients. I think it’s a great place for shared decision-making because if a patient hears about that and decides they’re not interested, I’ll be fine with that. I think that’s a very sensible approach, but I don’t want to make it unilaterally. Other patients may say they want every opportunity, and if it comes back, at least I’ll know I did everything we could.
Dr. Rotow: Exactly. I agree with your statement about equipoise. I truly think that this is present here in the situation, and that there’s room for discussion in both directions with patients.
Now, one caveat I’d like to add to all these data is that the data should not apply to patients with some of our classic nonsmoking-associated driver mutations. This is another piece to the neoadjuvant data that I think is worth commenting on – the need to get appropriate testing before initiation of therapy and the pitfalls of starting this kind of treatment without knowing full biomarker testing. I think that’s something we have to watch for in our clinical practice as well.
Dr. West: Perhaps especially if we’re talking about doing a year of postoperative and someone has an ALK rearrangement or an EGFR mutation and we didn’t know it. That is a group where we’re worried about a rapid transition and potentially prohibitive, even life-threatening, toxicities from not planning in advance for this. This is something you don’t want to give concurrently or one right on top of the other. You don’t want to give immunotherapy and then transition right to targeted therapy. It’s dangerous.
Dr. Rotow: Exactly. The stakes were already high with neoadjuvant alone, but at least you had that gap of the presurgical period, surgical recovery, and then initiation of adjuvant therapy, if needed, or at relapse. With a postoperative long adjuvant period, those stakes are elevated because the immunotherapy exposure continues, so it’s something to be mindful of.
Dr. West: We have a general sense that many, but not all, of the targets that we’re talking about are associated with low benefit from immunotherapy. It’s not that well studied. I think this is another place for individualized discussion of the pros and cons. They were included in the trial, but they probably benefit less.
Dr. Rotow: Exactly. I think with the best established, EGFR and ALK probably are not benefiting much. They were actually included in the trial. Many of the neoadjuvant studies do not allow them to enroll if they’re known. On the other end of that spectrum, I think KRAS is just fine to treat with immunotherapy.
Dr. West: Sure.
Dr. Rotow: It’s an actionable driver. It’s not a traditional nonsmoking-associated driver, and those do just fine.
Dr. West: The studies show that these patients benefit just as much, at least, as the other patients.
Dr. Rotow: Exactly. I would never withhold this form of therapy for a KRAS driver mutation. The others, I think, are still in a gray zone. Depending on the patient demographics and tobacco use, I may elicit more or less caution in that space.
Dr. West: Well, I think we’re going to have much to still tease apart, with room for judgment here without a strong sense of the data telling us exactly what to do.
Dr. Rotow: Exactly.
Dr. West: There’s a large amount of excitement and interest in these new data, but there are still many open questions. I hope we continue to mull it over as we get more data and more insight to shape our plans.
Dr. West is an associate professor at City of Hope Comprehensive Cancer Center in Duarte, Calif., and vice president of network strategy at AccessHope in Los Angeles. Dr. Rotow is the clinical director of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute in Boston. Dr. West reported conflicts of interest with Ariad/Takeda, Bristol Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly. Dr. Rotow reported conflicts of interest with Genentech, AstraZeneca,Guardant, and Janssen.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Dr. West: Here at ASCO 2023 [American Society of Clinical Oncology] in Chicago, we’ve seen some blockbuster presentations in thoracic oncology. Many of these have brought up some important questions about the clinical implications that we need to discuss further.
At ASCO, as well as in the couple or 3 months preceding ASCO, we’ve gotten more and more data on perioperative approaches. Of course, over the past couple of years, we’ve had some new options of postoperative immunotherapy for a year, say, after chemotherapy or possibly after chemotherapy.
We have also had very influential data, such as the CheckMate 816 trial that gave three cycles of chemotherapy with nivolumab vs. chemotherapy alone to patients with stage IB to IIIA disease, but largely, nearly two thirds, with IIIA disease. That showed a very clear improvement in the pathologic complete response (pCR) rate with nivolumab added to chemotherapy and also a highly significant improvement in event-free survival and a strong trend toward improved overall survival. This is FDA approved and has been increasingly adopted, I would say, maybe with some variability by geography and center, but really a good amount of enthusiasm.
Now, we have a bunch of trials that give chemotherapy with immunotherapy. We’ve got the AEGEAN trial with durvalumab. We have Neotorch with chemotherapy and toripalimab. At ASCO 2023, we had a highly prominent presentation of KEYNOTE-671, giving four cycles of chemotherapy with pembrolizumab vs. chemotherapy and placebo.
Then there’s the built-in postoperative component of a year of immunotherapy as well, in all these trials. The data for KEYNOTE-671 look quite good. Of course, the other trials also were significant. I would say the comparator now is not nothing or chemotherapy alone anymore; it’s really against what is the best current standard of care.
It certainly adds some cost, it adds some risk for toxicity, and it adds a year of a patient coming into the clinic and getting IV infusions all this time to get a treatment that the patient has already had for four cycles in most of these trials.
If your cancer is resistant, is there going to be an incremental benefit to giving more of it? What are your thoughts about the risk and benefit? Going to a patient in your own clinic, how are you going to counsel your patients? Will anything change after the presentation of all these data and how you approach preoperatively?
Dr. Rotow: I agree. In some sense, it’s an embarrassment of riches, right?
Dr. West: Yes.
Dr. Rotow: We have so many positive studies looking at perioperative immunotherapy for our patients. They all show improved outcomes, but of course, they all compare with the old control arm of chemotherapy alone in some form, and this is no longer a useful control in this space. The open question is, do you use neoadjuvant, do you use adjuvant, or do you use both?
My high-level takeaway from these data is that the neoadjuvant component appears to be important. I think the overall trend, comparing across studies, of course, is that outcomes seem to be better with the neoadjuvant component. You also get the advantage of potential downstaging and potential greater ease of surgical resection. We know they have lower morbidity resection and shorter surgeries. You can comment on that. You also get your pathologic response data.
Dr. West: You get the feedback.
Dr. Rotow: Exactly.
Dr. West: The deliverability is also a big issue. You know you can much more reliably deliver your intended treatment by doing neoadjuvant followed by surgery.
Dr. Rotow: Exactly.
Dr. West: We know there’s major drop-off if patients have surgery, and in the recovery room they hear you got it all, and then they need to come back and maybe get chemotherapy and immunotherapy for a year. They’d ask, “What for? I can’t see anything.”
Dr. Rotow: Exactly. I think there are many advantages to that neoadjuvant component. I think all or many of us now have integrated this into our routine practice. Now the question is, do you need the adjuvant element or not on top? That is challenging because no trial has compared adjuvant to nonadjuvant. I think we all advocate for the need for this trial to answer this in a more randomized, prospective fashion. Of course, that doesn’t help our clinic practice tomorrow when we see a patient.
Dr. West: Or for the next 4 years.
Dr. Rotow: Or for the next 4 years – exactly. There’s going to be the open question of who really needs this? In some sense, we may be guided by the path response during the surgery itself. I think there may be those who claim that if you have a pCR, do you really need additional therapy? We don’t know the answer, but it’s tempting to say we know the outcomes in event-free survival are extremely good with a pCR.
Dr. West: Which is only 20% or 25% of patients, so it’s not most.
Dr. Rotow: It’s not most, but it’s better than the 2% or so with chemotherapy alone. That’s real progress, and it’s nice to have that readout. For that 80% without a pCR, what to do? I suspect there will be variation from provider to provider and from patient to patient, depending on tolerability to prior therapy, the patient’s wishes around the goals of care, and the patient’s risk for autoimmune toxicities.
Maybe there’s a patient with underlying autoimmune disease who’s gotten their neoadjuvant therapy and done well. You don’t want to risk that ongoing risk of exposure. Perhaps a patient with no risk factors who desires very aggressive treatment might be interested in more treatment.
In KEYNOTE-671, I was interested in the PD-L1 subgroups. These did trend the way you expect, with better responses in PD-L1 high, but there were also good outcomes and benefit to immunotherapy with the perioperative strategy in PD-L1–negative patients.
Dr. West: That didn’t really exclude anybody.
Dr. Rotow: It didn’t exclude anybody. In CheckMate 816, everyone benefited, but the benefit was less with those PD-L1–negative patients.
Dr. West: True.
Dr. Rotow: Absent further data to guide me or any prospective data here comparing these strategies, I might lean toward a longer course of immunotherapy in that population in hopes of triggering a response. I suspect that there will be variation from clinician to clinician in that space.
Dr. West: This is a setting where I feel like I have equipoise. I really feel that the incremental benefit is pretty small.
Dr. Rotow: Small. I agree.
Dr. West: It’s, frankly, somewhat dubious. On the other hand, you’re in a situation where if you know that three of four patients will experience a relapse and less-than-amazing outcomes, it’s hard to leave something that’s FDA approved and studied and a well-sanctioned option on the table if this patient may have relapse later.
In the end, I feel like I’d like to offer this and discuss it with all my patients. I think it’s a great place for shared decision-making because if a patient hears about that and decides they’re not interested, I’ll be fine with that. I think that’s a very sensible approach, but I don’t want to make it unilaterally. Other patients may say they want every opportunity, and if it comes back, at least I’ll know I did everything we could.
Dr. Rotow: Exactly. I agree with your statement about equipoise. I truly think that this is present here in the situation, and that there’s room for discussion in both directions with patients.
Now, one caveat I’d like to add to all these data is that the data should not apply to patients with some of our classic nonsmoking-associated driver mutations. This is another piece to the neoadjuvant data that I think is worth commenting on – the need to get appropriate testing before initiation of therapy and the pitfalls of starting this kind of treatment without knowing full biomarker testing. I think that’s something we have to watch for in our clinical practice as well.
Dr. West: Perhaps especially if we’re talking about doing a year of postoperative and someone has an ALK rearrangement or an EGFR mutation and we didn’t know it. That is a group where we’re worried about a rapid transition and potentially prohibitive, even life-threatening, toxicities from not planning in advance for this. This is something you don’t want to give concurrently or one right on top of the other. You don’t want to give immunotherapy and then transition right to targeted therapy. It’s dangerous.
Dr. Rotow: Exactly. The stakes were already high with neoadjuvant alone, but at least you had that gap of the presurgical period, surgical recovery, and then initiation of adjuvant therapy, if needed, or at relapse. With a postoperative long adjuvant period, those stakes are elevated because the immunotherapy exposure continues, so it’s something to be mindful of.
Dr. West: We have a general sense that many, but not all, of the targets that we’re talking about are associated with low benefit from immunotherapy. It’s not that well studied. I think this is another place for individualized discussion of the pros and cons. They were included in the trial, but they probably benefit less.
Dr. Rotow: Exactly. I think with the best established, EGFR and ALK probably are not benefiting much. They were actually included in the trial. Many of the neoadjuvant studies do not allow them to enroll if they’re known. On the other end of that spectrum, I think KRAS is just fine to treat with immunotherapy.
Dr. West: Sure.
Dr. Rotow: It’s an actionable driver. It’s not a traditional nonsmoking-associated driver, and those do just fine.
Dr. West: The studies show that these patients benefit just as much, at least, as the other patients.
Dr. Rotow: Exactly. I would never withhold this form of therapy for a KRAS driver mutation. The others, I think, are still in a gray zone. Depending on the patient demographics and tobacco use, I may elicit more or less caution in that space.
Dr. West: Well, I think we’re going to have much to still tease apart, with room for judgment here without a strong sense of the data telling us exactly what to do.
Dr. Rotow: Exactly.
Dr. West: There’s a large amount of excitement and interest in these new data, but there are still many open questions. I hope we continue to mull it over as we get more data and more insight to shape our plans.
Dr. West is an associate professor at City of Hope Comprehensive Cancer Center in Duarte, Calif., and vice president of network strategy at AccessHope in Los Angeles. Dr. Rotow is the clinical director of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute in Boston. Dr. West reported conflicts of interest with Ariad/Takeda, Bristol Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly. Dr. Rotow reported conflicts of interest with Genentech, AstraZeneca,Guardant, and Janssen.
A version of this article first appeared on Medscape.com.
FROM ASCO 2023
Early-life antibiotic use may raise risk of early-onset CRC
TOPLINE:
, particularly in people with a variant in a specific gut microbiota regulatory gene, a new analysis found.
METHODOLOGY:
- Researchers analyzed data from UK Biobank participants who were recruited between 2006 and 2010 and were followed up to February 2022.
- They evaluated associations between early-life factors and early-onset CRC risk overall, focusing on long-term and recurrent antibiotic use.
- The team also estimated associations between long-term and recurrent antibiotic use in early life and CRC risk by polygenic risk score using 127 CRC-related genetic variants, as well as a particular gut microbiota regulatory gene FUT2.
- Associations for early-onset colorectal adenomas, as precursor to CRC, were also evaluated.
- The study included 113,256 participants. There were 165 early-onset CRC cases and 719 early-onset adenoma cases.
TAKEAWAY:
- Early-life, long-term, and recurrent antibiotic use was “nominally” associated with an increased risk of early-onset CRC (odds ratio, 1.48; P = .046) and adenomas (OR, 1.40; P < .001).
- Regarding variants of FUT2, the risk of early-onset CRC appeared to be greater for individuals with the rs281377 TT genotype (OR, 2.74) in comparison with those with the CT and TT genotypes, but none of the estimates reached statistical significance.
- The researchers found a strong positive association between long-term and recurrent antibiotic use and adenomas, largely in patients with rs281377 TT (OR, 1.75) and CT genotypes (OR, 1.51).
- Individuals with a high polygenic risk score were at higher risk of early-onset CRC (OR, 1.72; P = .019), while those with low polygenic risk scores were not at higher risk (OR, 1.05; P = .889). The association between antibiotic use and early-onset CRC risk by family history was also higher (OR, 2.34).
IN PRACTICE:
“Our findings suggested that individuals with genetic risk factors (i.e., family history of CRC) who have experienced early-life antibiotics use on a long-term basis are probably at increased early-onset CRC risk,” the authors concluded. “Given that antibiotics remain valuable in the management of bacterial infections during early life, investigating the pros and cons of early-life antibiotic use is of great significance.”
SOURCE:
The study, led by Fangyuan Jiang, with Zhejiang University, Hangzhou, China, was published online in the International Journal of Cancer.
LIMITATIONS:
The study relied on participants’ recall of early-life antibiotics use, which could introduce recall bias and misclassification of this exposure.
DISCLOSURES:
No conflicts of interest were reported.
A version of this article first appeared on Medscape.com.
TOPLINE:
, particularly in people with a variant in a specific gut microbiota regulatory gene, a new analysis found.
METHODOLOGY:
- Researchers analyzed data from UK Biobank participants who were recruited between 2006 and 2010 and were followed up to February 2022.
- They evaluated associations between early-life factors and early-onset CRC risk overall, focusing on long-term and recurrent antibiotic use.
- The team also estimated associations between long-term and recurrent antibiotic use in early life and CRC risk by polygenic risk score using 127 CRC-related genetic variants, as well as a particular gut microbiota regulatory gene FUT2.
- Associations for early-onset colorectal adenomas, as precursor to CRC, were also evaluated.
- The study included 113,256 participants. There were 165 early-onset CRC cases and 719 early-onset adenoma cases.
TAKEAWAY:
- Early-life, long-term, and recurrent antibiotic use was “nominally” associated with an increased risk of early-onset CRC (odds ratio, 1.48; P = .046) and adenomas (OR, 1.40; P < .001).
- Regarding variants of FUT2, the risk of early-onset CRC appeared to be greater for individuals with the rs281377 TT genotype (OR, 2.74) in comparison with those with the CT and TT genotypes, but none of the estimates reached statistical significance.
- The researchers found a strong positive association between long-term and recurrent antibiotic use and adenomas, largely in patients with rs281377 TT (OR, 1.75) and CT genotypes (OR, 1.51).
- Individuals with a high polygenic risk score were at higher risk of early-onset CRC (OR, 1.72; P = .019), while those with low polygenic risk scores were not at higher risk (OR, 1.05; P = .889). The association between antibiotic use and early-onset CRC risk by family history was also higher (OR, 2.34).
IN PRACTICE:
“Our findings suggested that individuals with genetic risk factors (i.e., family history of CRC) who have experienced early-life antibiotics use on a long-term basis are probably at increased early-onset CRC risk,” the authors concluded. “Given that antibiotics remain valuable in the management of bacterial infections during early life, investigating the pros and cons of early-life antibiotic use is of great significance.”
SOURCE:
The study, led by Fangyuan Jiang, with Zhejiang University, Hangzhou, China, was published online in the International Journal of Cancer.
LIMITATIONS:
The study relied on participants’ recall of early-life antibiotics use, which could introduce recall bias and misclassification of this exposure.
DISCLOSURES:
No conflicts of interest were reported.
A version of this article first appeared on Medscape.com.
TOPLINE:
, particularly in people with a variant in a specific gut microbiota regulatory gene, a new analysis found.
METHODOLOGY:
- Researchers analyzed data from UK Biobank participants who were recruited between 2006 and 2010 and were followed up to February 2022.
- They evaluated associations between early-life factors and early-onset CRC risk overall, focusing on long-term and recurrent antibiotic use.
- The team also estimated associations between long-term and recurrent antibiotic use in early life and CRC risk by polygenic risk score using 127 CRC-related genetic variants, as well as a particular gut microbiota regulatory gene FUT2.
- Associations for early-onset colorectal adenomas, as precursor to CRC, were also evaluated.
- The study included 113,256 participants. There were 165 early-onset CRC cases and 719 early-onset adenoma cases.
TAKEAWAY:
- Early-life, long-term, and recurrent antibiotic use was “nominally” associated with an increased risk of early-onset CRC (odds ratio, 1.48; P = .046) and adenomas (OR, 1.40; P < .001).
- Regarding variants of FUT2, the risk of early-onset CRC appeared to be greater for individuals with the rs281377 TT genotype (OR, 2.74) in comparison with those with the CT and TT genotypes, but none of the estimates reached statistical significance.
- The researchers found a strong positive association between long-term and recurrent antibiotic use and adenomas, largely in patients with rs281377 TT (OR, 1.75) and CT genotypes (OR, 1.51).
- Individuals with a high polygenic risk score were at higher risk of early-onset CRC (OR, 1.72; P = .019), while those with low polygenic risk scores were not at higher risk (OR, 1.05; P = .889). The association between antibiotic use and early-onset CRC risk by family history was also higher (OR, 2.34).
IN PRACTICE:
“Our findings suggested that individuals with genetic risk factors (i.e., family history of CRC) who have experienced early-life antibiotics use on a long-term basis are probably at increased early-onset CRC risk,” the authors concluded. “Given that antibiotics remain valuable in the management of bacterial infections during early life, investigating the pros and cons of early-life antibiotic use is of great significance.”
SOURCE:
The study, led by Fangyuan Jiang, with Zhejiang University, Hangzhou, China, was published online in the International Journal of Cancer.
LIMITATIONS:
The study relied on participants’ recall of early-life antibiotics use, which could introduce recall bias and misclassification of this exposure.
DISCLOSURES:
No conflicts of interest were reported.
A version of this article first appeared on Medscape.com.
FROM INTERNATIONAL JOURNAL OF CANCER
Prior auth is a self-inflicted wound; is there a way out?
A few months ago, a close friend called me in a panic.
Her mother had been on an oral treatment for relapsed multiple myeloma for nearly 1 year. Originally, she had been prescribed the oral pill pomalidomide as part of her regimen, but it had caused cytopenias, constipation, and nausea even at lower doses. Now, she was tolerating her new pill, ixazomib, quite well.
Then, without so much as a letter from her insurance company, the patient’s pharmacy called to tell her that ixazomib was no longer covered without a peer-to-peer conversation given its cost.
The peer to peer left the oncology team and patient even more frustrated. After leaving the team on hold for nearly an hour, the insurance company denied the request for ixazomib. The hematologist conducting the peer-to-peer did not seem to understand why the patient had discontinued her previous medication.
Ultimately, the patient was forced to return to the old, less expensive drug. Since going back to pomalidomide, she has needed multiple dosing changes to manage the intense drug side effects.
I wish that stories like this were uncommon. I am often reminded of the ongoing challenges related to prior authorization when I see colleagues regaling the Twitterverse with their latest horror stories about an insurance company rejecting standard of care treatment or imaging. The data confirm the frequency of these experiences. Among a general cohort of physicians, the American Medical Association has reported that most practices complete 29 prior authorizations per physician every week and spend on average 14.6 hours, or nearly 2 full business days, of staff time each week on these requirements.
Given the growing burden of prior authorization, reform has now become a major policy issue at the federal and state level. Within the past year, organizations like the American Society of Clinical Oncology have released policy positions on prior authorization and are devoting sizable advocacy dollars to fight payers’ ability to enact it. Entire sections of the ASCO education book are devoted to detailing the negative effects of prior authorization, and recent ASCO-commissioned surveys have highlighted alarming statistics about how prior authorization harms patient care.
As a practicing oncologist, I welcome increased attention to the burdens of prior authorization. This attention shows that our professional organizations care about one of the largest contributors to burnout.
But as a researcher who studies systems of care, I worry that focusing our collective ire on health insurance companies is somewhat misplaced or unlikely to succeed.
Why? Because policy statements, Tweets, and legislation ignore the fact that prior authorization is a self-inflicted wound caused by decades of pharmaceutical companies, health systems, oncologists, and guideline bodies failing to factor costs of care into clinical practice.
Making cost-conscious oncology care a priority would be ideal, but it is also a tall order.
But, as costs continue to rise uncontrollably, the prior authorization system has ballooned out of control and reining in this system will be quite a challenge. Perhaps, we can look to my oncology practice at a Veterans Affairs Medical Center as a guide.
A self-inflicted wound
In oncology, most medications and imaging are subject to prior authorization, particularly higher-cost items, and dealing with prior authorization typically requires an army of staff. As enrollment in commercial health plans or Medicare Advantage skyrockets, prior authorization will only become more prevalent in oncology.
Why is this happening?
The lazy answer to this question is because health insurance companies put profits over patients.
However, prior authorization is a symptom, not a disease. And that symptom is exploding cancer care costs. The causes of high costs are varied: Pharmaceutical companies and device manufacturers set ungodly prices for drugs; oncologists and other specialists are often reimbursed for volume of care, not quality; and hospitals and health systems charge incredible amounts for routine labs and imaging, amounts that are orders of magnitude higher than what these services actually cost.
There is no easy solution to fix the drivers of such costs. One approach to rein in drug costs would be to allow Medicare to negotiate drug prices and set site-neutral pricing.
Another would be to incentivize doctors or health systems to reduce the use of high-cost services. But physicians are often unaware of the costs of a given treatment to a system or patient, and practices reimbursed by volume of care typically have little incentive to curb overall spending.
We are then left with payers, the primary means of reimbursing care and, specifically, utilization management, such as prior authorization and restrictive formularies, as the major mechanism to reduce this spending.
Prior authorization is broken
Here’s the rub though: Although payers are incentivized to curb costs through prior authorization, the data that they have to adjudicate therapeutic appropriateness are often terrible.
Administrative claims contain no data on biomarkers or performance status and are notoriously bad at reflecting basic information, such as a patient’s stage of cancer. For instance, the positive predictive value of claims-based algorithms to identify stage IV breast cancer is well below 50%, meaning that a claims algorithm that classifies a patient as stage IV is wrong more often than right.
If payers had better data, they could be more selective in their prior-authorization requirements. In other words, if payers could reliably identify who has metastatic breast cancer, an aromatase inhibitor, a common, well-accepted adjuvant therapy in hormone-positive, late-stage breast cancer, wouldn’t need prior authorization. What we have now is an inefficient system that sets prior authorization as a guardrail for most oncology care and then forces doctors to submit all relevant information about a patient to justify their treatment choices.
Keeping up with oncology treatment advances is also a challenge and requires tremendous expertise. Many insurers delegate their prior-authorization responsibilities to medication management companies, such as Magellan Rx or New Century Health, who maintain proprietary treatment pathways.
These companies anchor their prior authorization requirements to common guidelines. That would be fine if guideline-producing bodies like the National Comprehensive Cancer Network provided more firm recommendations on high-value treatments.
The NCCN recommendations, however, are expert-driven more than evidence or value driven. Often, therapies with less evidence make it into recommended treatment guidelines, and in some cases, the NCCN will equally recommend five options for treating a certain cancer, even when there is an obvious lower-cost option.
The effect of this, however, is that payers may then cover these five options, despite a 40-fold price difference among them, but then lean on requiring prior authorization for everything rather than being selective. Broad rather than targeted use of prior authorization alongside well-known issue like uncertain time lines, huge numbers of forms, and nonexperts doing peer to peers make for a huge mess.
What can we do?
How can we begin to solve the prior authorization crisis? A first step would be for guideline bodies to have more teeth in their recommendations. If NCCN and other guideline bodies, for instance, incorporated cost into their recommendations and designated these as “preferred” regimens, then clinicians could have better direction on therapy selection and payers could align their prior authorization policies with those recommendations. If patients had adverse effects with low-cost drugs, then a preferred alternative could be specified in such guidelines rather than subject patients, like my friend’s mother, to a toxic drug.
Second, payers could tailor the intensity of prior authorization requirements to the type of physician and clinical scenario at hand. Payers have rich data on practice patterns of oncologists. Payers should incentivize oncologists who follow guideline-based, high-value treatment pathways by lowering the need for frequent peer-to-peers or other prior authorization for “good performers.” This strategy, often termed gold carding, would use relief from prior authorization as a carrot.
Similarly, payers could reward practices that implement clinical pathways that enforce high-value care. For example, a practice could develop a treatment pathway that emphasizes access to urgent care to avoid hospitalizations as well as prioritizes access to relatively lower cost but equally effective options for therapy. If a payer reviewed and approved the pathway, perhaps payers could propose relief of future prior authorizations for practices whose oncologist practice on this pathway.
Third, payers could step up the intensity of prior authorization for certain high-cost or low-value treatments and lessen requirements for more routine services. For example, if every initial staging PET-CT required a peer to peer, oncologists would spend most of the day on the phone. Rather, lower-level tasks such as imaging may require a simple electronic EHR message, whereas high-cost items such as indefinite systemic therapy may require more frequent peer to peers.
Fourth, health systems and real-world data companies should devise better data sharing partnerships with payers so that payers could automatically examine attributes that clarify the choice of therapy. For example, if a payer could view that a patient had estrogen receptor/progesterone receptor–positive early-stage breast cancer post surgery, perhaps that payer would not require a prior authorization for an aromatase inhibitor. These real-time data sharing partnerships could reduce friction points in the system.
Finally, researchers and other groups should partner with payers to continually examine the effectiveness of any prior-authorization program. If a prior-authorization policy is no longer effective because evidence changes and evolves, then payers should consider retiring it.
In my primary oncology practice at a VA Medical Center, none of my treatments require an external prior authorization. Why? Because our local practice agreed to an established formulary, and national treatment pathways firmly specify a recommended treatment course.
Do I sometimes go off pathway? Yes, when I feel there’s a compelling reason. But that requires a structured electronic form to a central pharmacy body. I get a response within 24 hours, with no onerous prior authorization form or lengthy peer to peer.
Though there are plenty of unique qualities about the VA, the fact is that health systems and guideline bodies assuming the burden of cost containment could reduce prior-authorization requirements from payers.
Ultimately, the goal should be for oncologists to choose the highest-value treatment possible. Perhaps then, when the end-goal of cost-conscious oncology care with payers maintain an arm’s length from the patient-doctor relationship, we could all stop shouting at the wind about the burden of prior authorization.
Dr. Parikh is a medical oncologist and faculty member at the University of Pennsylvania, Philadelphia, and the Philadelphia VA Medical Center, an adjunct fellow at the Leonard Davis Institute of Health Economics, and senior clinical advisor at the Coalition to Transform Advanced Care. He reported conflicts of interest with GNS Healthcare, Nanology, Cancer Study Group, Embedded Healthcare, Veterans Affairs, PCF, National Palliative Care Research Center, MUSC, and Flatiron Health.
A version of this article first appeared on Medscape.com.
A few months ago, a close friend called me in a panic.
Her mother had been on an oral treatment for relapsed multiple myeloma for nearly 1 year. Originally, she had been prescribed the oral pill pomalidomide as part of her regimen, but it had caused cytopenias, constipation, and nausea even at lower doses. Now, she was tolerating her new pill, ixazomib, quite well.
Then, without so much as a letter from her insurance company, the patient’s pharmacy called to tell her that ixazomib was no longer covered without a peer-to-peer conversation given its cost.
The peer to peer left the oncology team and patient even more frustrated. After leaving the team on hold for nearly an hour, the insurance company denied the request for ixazomib. The hematologist conducting the peer-to-peer did not seem to understand why the patient had discontinued her previous medication.
Ultimately, the patient was forced to return to the old, less expensive drug. Since going back to pomalidomide, she has needed multiple dosing changes to manage the intense drug side effects.
I wish that stories like this were uncommon. I am often reminded of the ongoing challenges related to prior authorization when I see colleagues regaling the Twitterverse with their latest horror stories about an insurance company rejecting standard of care treatment or imaging. The data confirm the frequency of these experiences. Among a general cohort of physicians, the American Medical Association has reported that most practices complete 29 prior authorizations per physician every week and spend on average 14.6 hours, or nearly 2 full business days, of staff time each week on these requirements.
Given the growing burden of prior authorization, reform has now become a major policy issue at the federal and state level. Within the past year, organizations like the American Society of Clinical Oncology have released policy positions on prior authorization and are devoting sizable advocacy dollars to fight payers’ ability to enact it. Entire sections of the ASCO education book are devoted to detailing the negative effects of prior authorization, and recent ASCO-commissioned surveys have highlighted alarming statistics about how prior authorization harms patient care.
As a practicing oncologist, I welcome increased attention to the burdens of prior authorization. This attention shows that our professional organizations care about one of the largest contributors to burnout.
But as a researcher who studies systems of care, I worry that focusing our collective ire on health insurance companies is somewhat misplaced or unlikely to succeed.
Why? Because policy statements, Tweets, and legislation ignore the fact that prior authorization is a self-inflicted wound caused by decades of pharmaceutical companies, health systems, oncologists, and guideline bodies failing to factor costs of care into clinical practice.
Making cost-conscious oncology care a priority would be ideal, but it is also a tall order.
But, as costs continue to rise uncontrollably, the prior authorization system has ballooned out of control and reining in this system will be quite a challenge. Perhaps, we can look to my oncology practice at a Veterans Affairs Medical Center as a guide.
A self-inflicted wound
In oncology, most medications and imaging are subject to prior authorization, particularly higher-cost items, and dealing with prior authorization typically requires an army of staff. As enrollment in commercial health plans or Medicare Advantage skyrockets, prior authorization will only become more prevalent in oncology.
Why is this happening?
The lazy answer to this question is because health insurance companies put profits over patients.
However, prior authorization is a symptom, not a disease. And that symptom is exploding cancer care costs. The causes of high costs are varied: Pharmaceutical companies and device manufacturers set ungodly prices for drugs; oncologists and other specialists are often reimbursed for volume of care, not quality; and hospitals and health systems charge incredible amounts for routine labs and imaging, amounts that are orders of magnitude higher than what these services actually cost.
There is no easy solution to fix the drivers of such costs. One approach to rein in drug costs would be to allow Medicare to negotiate drug prices and set site-neutral pricing.
Another would be to incentivize doctors or health systems to reduce the use of high-cost services. But physicians are often unaware of the costs of a given treatment to a system or patient, and practices reimbursed by volume of care typically have little incentive to curb overall spending.
We are then left with payers, the primary means of reimbursing care and, specifically, utilization management, such as prior authorization and restrictive formularies, as the major mechanism to reduce this spending.
Prior authorization is broken
Here’s the rub though: Although payers are incentivized to curb costs through prior authorization, the data that they have to adjudicate therapeutic appropriateness are often terrible.
Administrative claims contain no data on biomarkers or performance status and are notoriously bad at reflecting basic information, such as a patient’s stage of cancer. For instance, the positive predictive value of claims-based algorithms to identify stage IV breast cancer is well below 50%, meaning that a claims algorithm that classifies a patient as stage IV is wrong more often than right.
If payers had better data, they could be more selective in their prior-authorization requirements. In other words, if payers could reliably identify who has metastatic breast cancer, an aromatase inhibitor, a common, well-accepted adjuvant therapy in hormone-positive, late-stage breast cancer, wouldn’t need prior authorization. What we have now is an inefficient system that sets prior authorization as a guardrail for most oncology care and then forces doctors to submit all relevant information about a patient to justify their treatment choices.
Keeping up with oncology treatment advances is also a challenge and requires tremendous expertise. Many insurers delegate their prior-authorization responsibilities to medication management companies, such as Magellan Rx or New Century Health, who maintain proprietary treatment pathways.
These companies anchor their prior authorization requirements to common guidelines. That would be fine if guideline-producing bodies like the National Comprehensive Cancer Network provided more firm recommendations on high-value treatments.
The NCCN recommendations, however, are expert-driven more than evidence or value driven. Often, therapies with less evidence make it into recommended treatment guidelines, and in some cases, the NCCN will equally recommend five options for treating a certain cancer, even when there is an obvious lower-cost option.
The effect of this, however, is that payers may then cover these five options, despite a 40-fold price difference among them, but then lean on requiring prior authorization for everything rather than being selective. Broad rather than targeted use of prior authorization alongside well-known issue like uncertain time lines, huge numbers of forms, and nonexperts doing peer to peers make for a huge mess.
What can we do?
How can we begin to solve the prior authorization crisis? A first step would be for guideline bodies to have more teeth in their recommendations. If NCCN and other guideline bodies, for instance, incorporated cost into their recommendations and designated these as “preferred” regimens, then clinicians could have better direction on therapy selection and payers could align their prior authorization policies with those recommendations. If patients had adverse effects with low-cost drugs, then a preferred alternative could be specified in such guidelines rather than subject patients, like my friend’s mother, to a toxic drug.
Second, payers could tailor the intensity of prior authorization requirements to the type of physician and clinical scenario at hand. Payers have rich data on practice patterns of oncologists. Payers should incentivize oncologists who follow guideline-based, high-value treatment pathways by lowering the need for frequent peer-to-peers or other prior authorization for “good performers.” This strategy, often termed gold carding, would use relief from prior authorization as a carrot.
Similarly, payers could reward practices that implement clinical pathways that enforce high-value care. For example, a practice could develop a treatment pathway that emphasizes access to urgent care to avoid hospitalizations as well as prioritizes access to relatively lower cost but equally effective options for therapy. If a payer reviewed and approved the pathway, perhaps payers could propose relief of future prior authorizations for practices whose oncologist practice on this pathway.
Third, payers could step up the intensity of prior authorization for certain high-cost or low-value treatments and lessen requirements for more routine services. For example, if every initial staging PET-CT required a peer to peer, oncologists would spend most of the day on the phone. Rather, lower-level tasks such as imaging may require a simple electronic EHR message, whereas high-cost items such as indefinite systemic therapy may require more frequent peer to peers.
Fourth, health systems and real-world data companies should devise better data sharing partnerships with payers so that payers could automatically examine attributes that clarify the choice of therapy. For example, if a payer could view that a patient had estrogen receptor/progesterone receptor–positive early-stage breast cancer post surgery, perhaps that payer would not require a prior authorization for an aromatase inhibitor. These real-time data sharing partnerships could reduce friction points in the system.
Finally, researchers and other groups should partner with payers to continually examine the effectiveness of any prior-authorization program. If a prior-authorization policy is no longer effective because evidence changes and evolves, then payers should consider retiring it.
In my primary oncology practice at a VA Medical Center, none of my treatments require an external prior authorization. Why? Because our local practice agreed to an established formulary, and national treatment pathways firmly specify a recommended treatment course.
Do I sometimes go off pathway? Yes, when I feel there’s a compelling reason. But that requires a structured electronic form to a central pharmacy body. I get a response within 24 hours, with no onerous prior authorization form or lengthy peer to peer.
Though there are plenty of unique qualities about the VA, the fact is that health systems and guideline bodies assuming the burden of cost containment could reduce prior-authorization requirements from payers.
Ultimately, the goal should be for oncologists to choose the highest-value treatment possible. Perhaps then, when the end-goal of cost-conscious oncology care with payers maintain an arm’s length from the patient-doctor relationship, we could all stop shouting at the wind about the burden of prior authorization.
Dr. Parikh is a medical oncologist and faculty member at the University of Pennsylvania, Philadelphia, and the Philadelphia VA Medical Center, an adjunct fellow at the Leonard Davis Institute of Health Economics, and senior clinical advisor at the Coalition to Transform Advanced Care. He reported conflicts of interest with GNS Healthcare, Nanology, Cancer Study Group, Embedded Healthcare, Veterans Affairs, PCF, National Palliative Care Research Center, MUSC, and Flatiron Health.
A version of this article first appeared on Medscape.com.
A few months ago, a close friend called me in a panic.
Her mother had been on an oral treatment for relapsed multiple myeloma for nearly 1 year. Originally, she had been prescribed the oral pill pomalidomide as part of her regimen, but it had caused cytopenias, constipation, and nausea even at lower doses. Now, she was tolerating her new pill, ixazomib, quite well.
Then, without so much as a letter from her insurance company, the patient’s pharmacy called to tell her that ixazomib was no longer covered without a peer-to-peer conversation given its cost.
The peer to peer left the oncology team and patient even more frustrated. After leaving the team on hold for nearly an hour, the insurance company denied the request for ixazomib. The hematologist conducting the peer-to-peer did not seem to understand why the patient had discontinued her previous medication.
Ultimately, the patient was forced to return to the old, less expensive drug. Since going back to pomalidomide, she has needed multiple dosing changes to manage the intense drug side effects.
I wish that stories like this were uncommon. I am often reminded of the ongoing challenges related to prior authorization when I see colleagues regaling the Twitterverse with their latest horror stories about an insurance company rejecting standard of care treatment or imaging. The data confirm the frequency of these experiences. Among a general cohort of physicians, the American Medical Association has reported that most practices complete 29 prior authorizations per physician every week and spend on average 14.6 hours, or nearly 2 full business days, of staff time each week on these requirements.
Given the growing burden of prior authorization, reform has now become a major policy issue at the federal and state level. Within the past year, organizations like the American Society of Clinical Oncology have released policy positions on prior authorization and are devoting sizable advocacy dollars to fight payers’ ability to enact it. Entire sections of the ASCO education book are devoted to detailing the negative effects of prior authorization, and recent ASCO-commissioned surveys have highlighted alarming statistics about how prior authorization harms patient care.
As a practicing oncologist, I welcome increased attention to the burdens of prior authorization. This attention shows that our professional organizations care about one of the largest contributors to burnout.
But as a researcher who studies systems of care, I worry that focusing our collective ire on health insurance companies is somewhat misplaced or unlikely to succeed.
Why? Because policy statements, Tweets, and legislation ignore the fact that prior authorization is a self-inflicted wound caused by decades of pharmaceutical companies, health systems, oncologists, and guideline bodies failing to factor costs of care into clinical practice.
Making cost-conscious oncology care a priority would be ideal, but it is also a tall order.
But, as costs continue to rise uncontrollably, the prior authorization system has ballooned out of control and reining in this system will be quite a challenge. Perhaps, we can look to my oncology practice at a Veterans Affairs Medical Center as a guide.
A self-inflicted wound
In oncology, most medications and imaging are subject to prior authorization, particularly higher-cost items, and dealing with prior authorization typically requires an army of staff. As enrollment in commercial health plans or Medicare Advantage skyrockets, prior authorization will only become more prevalent in oncology.
Why is this happening?
The lazy answer to this question is because health insurance companies put profits over patients.
However, prior authorization is a symptom, not a disease. And that symptom is exploding cancer care costs. The causes of high costs are varied: Pharmaceutical companies and device manufacturers set ungodly prices for drugs; oncologists and other specialists are often reimbursed for volume of care, not quality; and hospitals and health systems charge incredible amounts for routine labs and imaging, amounts that are orders of magnitude higher than what these services actually cost.
There is no easy solution to fix the drivers of such costs. One approach to rein in drug costs would be to allow Medicare to negotiate drug prices and set site-neutral pricing.
Another would be to incentivize doctors or health systems to reduce the use of high-cost services. But physicians are often unaware of the costs of a given treatment to a system or patient, and practices reimbursed by volume of care typically have little incentive to curb overall spending.
We are then left with payers, the primary means of reimbursing care and, specifically, utilization management, such as prior authorization and restrictive formularies, as the major mechanism to reduce this spending.
Prior authorization is broken
Here’s the rub though: Although payers are incentivized to curb costs through prior authorization, the data that they have to adjudicate therapeutic appropriateness are often terrible.
Administrative claims contain no data on biomarkers or performance status and are notoriously bad at reflecting basic information, such as a patient’s stage of cancer. For instance, the positive predictive value of claims-based algorithms to identify stage IV breast cancer is well below 50%, meaning that a claims algorithm that classifies a patient as stage IV is wrong more often than right.
If payers had better data, they could be more selective in their prior-authorization requirements. In other words, if payers could reliably identify who has metastatic breast cancer, an aromatase inhibitor, a common, well-accepted adjuvant therapy in hormone-positive, late-stage breast cancer, wouldn’t need prior authorization. What we have now is an inefficient system that sets prior authorization as a guardrail for most oncology care and then forces doctors to submit all relevant information about a patient to justify their treatment choices.
Keeping up with oncology treatment advances is also a challenge and requires tremendous expertise. Many insurers delegate their prior-authorization responsibilities to medication management companies, such as Magellan Rx or New Century Health, who maintain proprietary treatment pathways.
These companies anchor their prior authorization requirements to common guidelines. That would be fine if guideline-producing bodies like the National Comprehensive Cancer Network provided more firm recommendations on high-value treatments.
The NCCN recommendations, however, are expert-driven more than evidence or value driven. Often, therapies with less evidence make it into recommended treatment guidelines, and in some cases, the NCCN will equally recommend five options for treating a certain cancer, even when there is an obvious lower-cost option.
The effect of this, however, is that payers may then cover these five options, despite a 40-fold price difference among them, but then lean on requiring prior authorization for everything rather than being selective. Broad rather than targeted use of prior authorization alongside well-known issue like uncertain time lines, huge numbers of forms, and nonexperts doing peer to peers make for a huge mess.
What can we do?
How can we begin to solve the prior authorization crisis? A first step would be for guideline bodies to have more teeth in their recommendations. If NCCN and other guideline bodies, for instance, incorporated cost into their recommendations and designated these as “preferred” regimens, then clinicians could have better direction on therapy selection and payers could align their prior authorization policies with those recommendations. If patients had adverse effects with low-cost drugs, then a preferred alternative could be specified in such guidelines rather than subject patients, like my friend’s mother, to a toxic drug.
Second, payers could tailor the intensity of prior authorization requirements to the type of physician and clinical scenario at hand. Payers have rich data on practice patterns of oncologists. Payers should incentivize oncologists who follow guideline-based, high-value treatment pathways by lowering the need for frequent peer-to-peers or other prior authorization for “good performers.” This strategy, often termed gold carding, would use relief from prior authorization as a carrot.
Similarly, payers could reward practices that implement clinical pathways that enforce high-value care. For example, a practice could develop a treatment pathway that emphasizes access to urgent care to avoid hospitalizations as well as prioritizes access to relatively lower cost but equally effective options for therapy. If a payer reviewed and approved the pathway, perhaps payers could propose relief of future prior authorizations for practices whose oncologist practice on this pathway.
Third, payers could step up the intensity of prior authorization for certain high-cost or low-value treatments and lessen requirements for more routine services. For example, if every initial staging PET-CT required a peer to peer, oncologists would spend most of the day on the phone. Rather, lower-level tasks such as imaging may require a simple electronic EHR message, whereas high-cost items such as indefinite systemic therapy may require more frequent peer to peers.
Fourth, health systems and real-world data companies should devise better data sharing partnerships with payers so that payers could automatically examine attributes that clarify the choice of therapy. For example, if a payer could view that a patient had estrogen receptor/progesterone receptor–positive early-stage breast cancer post surgery, perhaps that payer would not require a prior authorization for an aromatase inhibitor. These real-time data sharing partnerships could reduce friction points in the system.
Finally, researchers and other groups should partner with payers to continually examine the effectiveness of any prior-authorization program. If a prior-authorization policy is no longer effective because evidence changes and evolves, then payers should consider retiring it.
In my primary oncology practice at a VA Medical Center, none of my treatments require an external prior authorization. Why? Because our local practice agreed to an established formulary, and national treatment pathways firmly specify a recommended treatment course.
Do I sometimes go off pathway? Yes, when I feel there’s a compelling reason. But that requires a structured electronic form to a central pharmacy body. I get a response within 24 hours, with no onerous prior authorization form or lengthy peer to peer.
Though there are plenty of unique qualities about the VA, the fact is that health systems and guideline bodies assuming the burden of cost containment could reduce prior-authorization requirements from payers.
Ultimately, the goal should be for oncologists to choose the highest-value treatment possible. Perhaps then, when the end-goal of cost-conscious oncology care with payers maintain an arm’s length from the patient-doctor relationship, we could all stop shouting at the wind about the burden of prior authorization.
Dr. Parikh is a medical oncologist and faculty member at the University of Pennsylvania, Philadelphia, and the Philadelphia VA Medical Center, an adjunct fellow at the Leonard Davis Institute of Health Economics, and senior clinical advisor at the Coalition to Transform Advanced Care. He reported conflicts of interest with GNS Healthcare, Nanology, Cancer Study Group, Embedded Healthcare, Veterans Affairs, PCF, National Palliative Care Research Center, MUSC, and Flatiron Health.
A version of this article first appeared on Medscape.com.
Increasing number of children being poisoned by liquid nicotine
Doctors say a 2016 law aimed at lowering the risk contained a big flaw, NBC News reported. The Child Nicotine Poisoning Prevention Act required child-resistant packaging on vaping liquid – but not on the vaping devices themselves.
Contact with the vaping liquid, or liquid nicotine, can cause children to get dizzy, pass out, and suffer drops in blood pressure. A few drops of the liquid can be fatal for a toddler.
Last year, 6,731 cases of vaping-related nicotine exposure were reported, according to Poison Help. “As of June 30, 2023, poison centers have managed 3,863 exposure cases about e-cigarette devices and liquid nicotine,” the organization said.
“Poison centers began receiving calls about e-cigarettes and liquid nicotine products in 2011, which coincides with the initial period where these products reached the U.S. market,” according to Poison Help.
“These products often contain a greater concentration of nicotine, a stimulant, than other nicotine/tobacco products on the market. Some children and toddlers who come in contact with e-cigarette devices or liquid nicotine have become very ill; some even requiring emergency department visits with nausea and vomiting being the most significant symptoms.”
Toxicologist Ryan Marino, MD, told NBC that refillable vapes are designed to hold liquid nicotine in a central reservoir, making them dangerous to children.
“Even vapes that appear more child-resistant – because their nicotine is sealed inside a removable cartridge – present a risk, because the cartridges can be pried open,” NBC said. “And some disposable e-cigarettes, now the top-selling type on the market, allow users to take thousands of ‘puffs’ and contain as much nicotine as multiple packs of cigarettes.”
A spokesperson for the vaping industry said all e-liquid bottles made in this country conform to U.S. law.
“Not only are the caps child-resistant, but the flow of liquid is restricted so that only small amounts can be dispensed,” said April Meyers of the Smoke-Free Alternatives Trade Association, which represents the vaping industry.
A version of this article first appeared on WebMD.com.
Doctors say a 2016 law aimed at lowering the risk contained a big flaw, NBC News reported. The Child Nicotine Poisoning Prevention Act required child-resistant packaging on vaping liquid – but not on the vaping devices themselves.
Contact with the vaping liquid, or liquid nicotine, can cause children to get dizzy, pass out, and suffer drops in blood pressure. A few drops of the liquid can be fatal for a toddler.
Last year, 6,731 cases of vaping-related nicotine exposure were reported, according to Poison Help. “As of June 30, 2023, poison centers have managed 3,863 exposure cases about e-cigarette devices and liquid nicotine,” the organization said.
“Poison centers began receiving calls about e-cigarettes and liquid nicotine products in 2011, which coincides with the initial period where these products reached the U.S. market,” according to Poison Help.
“These products often contain a greater concentration of nicotine, a stimulant, than other nicotine/tobacco products on the market. Some children and toddlers who come in contact with e-cigarette devices or liquid nicotine have become very ill; some even requiring emergency department visits with nausea and vomiting being the most significant symptoms.”
Toxicologist Ryan Marino, MD, told NBC that refillable vapes are designed to hold liquid nicotine in a central reservoir, making them dangerous to children.
“Even vapes that appear more child-resistant – because their nicotine is sealed inside a removable cartridge – present a risk, because the cartridges can be pried open,” NBC said. “And some disposable e-cigarettes, now the top-selling type on the market, allow users to take thousands of ‘puffs’ and contain as much nicotine as multiple packs of cigarettes.”
A spokesperson for the vaping industry said all e-liquid bottles made in this country conform to U.S. law.
“Not only are the caps child-resistant, but the flow of liquid is restricted so that only small amounts can be dispensed,” said April Meyers of the Smoke-Free Alternatives Trade Association, which represents the vaping industry.
A version of this article first appeared on WebMD.com.
Doctors say a 2016 law aimed at lowering the risk contained a big flaw, NBC News reported. The Child Nicotine Poisoning Prevention Act required child-resistant packaging on vaping liquid – but not on the vaping devices themselves.
Contact with the vaping liquid, or liquid nicotine, can cause children to get dizzy, pass out, and suffer drops in blood pressure. A few drops of the liquid can be fatal for a toddler.
Last year, 6,731 cases of vaping-related nicotine exposure were reported, according to Poison Help. “As of June 30, 2023, poison centers have managed 3,863 exposure cases about e-cigarette devices and liquid nicotine,” the organization said.
“Poison centers began receiving calls about e-cigarettes and liquid nicotine products in 2011, which coincides with the initial period where these products reached the U.S. market,” according to Poison Help.
“These products often contain a greater concentration of nicotine, a stimulant, than other nicotine/tobacco products on the market. Some children and toddlers who come in contact with e-cigarette devices or liquid nicotine have become very ill; some even requiring emergency department visits with nausea and vomiting being the most significant symptoms.”
Toxicologist Ryan Marino, MD, told NBC that refillable vapes are designed to hold liquid nicotine in a central reservoir, making them dangerous to children.
“Even vapes that appear more child-resistant – because their nicotine is sealed inside a removable cartridge – present a risk, because the cartridges can be pried open,” NBC said. “And some disposable e-cigarettes, now the top-selling type on the market, allow users to take thousands of ‘puffs’ and contain as much nicotine as multiple packs of cigarettes.”
A spokesperson for the vaping industry said all e-liquid bottles made in this country conform to U.S. law.
“Not only are the caps child-resistant, but the flow of liquid is restricted so that only small amounts can be dispensed,” said April Meyers of the Smoke-Free Alternatives Trade Association, which represents the vaping industry.
A version of this article first appeared on WebMD.com.
Thrombectomy improves outcomes in pediatric stroke
A matched case-control study followed 52 patients in Canada and Australia with acute stroke and assessed functional outcomes at 3 months for those who received thrombectomy, compared with those who did not. Patients receiving the procedure had significantly improved clinical outcomes (odds ratio [OR], 3.76). The procedure is the standard of care for adults with large vessel occlusion (LVO) stroke, but limited data exist for children.
“In the absence of a randomized trial, this case-control study demonstrates better clinical outcomes with thrombectomy than medical management for pediatric patients aged 2 to 18 years with anterior circulation LVO stroke,” the authors concluded. The study was published in JAMA Neurology.
Improved results
Untreated LVO stroke is associated with poor outcomes, indicated in this study with scoring based on the modified Rankin Scale. Based on this scoring, 53.8% of patients who were managed conservatively had poor outcomes (moderate disability or greater) at 3 months, confirming previous findings. The data were drawn from five hospitals in Australia and Canada between January 2011 and April 2022.
Removing blood clots with mechanical thrombectomy resulted in improved outcomes 3 months after stroke for the patients included in the study, compared with the neuroprotective measures of medical therapy alone. The improved outcomes persisted in the final available follow-up (OR, 3.65).
In adults, thrombectomy has previously been demonstrated to be a safe and effective treatment for LVO stroke and is currently the standard of care. This study sought to expand the data for pediatric patients, for whom stroke is rarer and difficult to diagnose.
The authors cautioned, however, that the outcomes are from hospitals with pediatric neurology expertise and should not be generalized to settings without specialists.
Case-control study
While previous population-based studies of children with LVO stroke found that conservative treatment was associated with poor outcomes, these studies may include significant selection bias. The investigators chose to conduct the case-control study as an alternative to a randomized control trial, which would require withholding treatment from some patients and would not be considered ethical.
The study included 26 patients in each cohort, either receiving mechanical thrombectomy or medical treatment alone. The investigators matched patients by site and side of occlusion, age, and sex. Cases that could not be matched by site of occlusion, the primary criterion, were excluded.
With this methodology, the investigators reduced the impact of selection bias with the aim of providing “the next highest level of comparative evidence,” they stated in the study. However, they also noted that, without randomization, there is likely still some selection bias present.
The two cohorts were not significantly different based on factors such as sex or age. All patients in the study presented within 24 hours of symptom onset, with most eligible for thrombectomy by adult standards. There was a difference between the two cohorts in the timing of arrival to a dedicated hospital and imaging. “Our triage, imaging, and decision-making pathways require streamlining,” the authors concluded, regarding the difference.
‘A heterogeneous condition’
In a comment, Ratika Srivastava, MD, a pediatric neurologist at the University of Alberta, Edmonton, said she was glad to see a well-designed study dedicated to pediatric stroke. Neurologists have traditionally extrapolated from research on adult stroke due to the rarity of pediatric stroke and difficulty of diagnosis.
While physicians have previously relied on findings in adults, stroke presents differently in children. “The challenge is that it’s such a heterogeneous condition,” said Dr. Srivastava, who was not involved in the study. In children, stroke may have several different etiologies, such as a lesion in the heart or arterial disease. “Sometimes it’s amenable to taking the clot out and sometimes it’s not. So you have to figure out: Are they a good candidate for thrombectomy?” This study helps demonstrate that thrombectomy is a good option for some children with LVO stroke, she said.
The study was independently supported. Dr. Srivastava reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A matched case-control study followed 52 patients in Canada and Australia with acute stroke and assessed functional outcomes at 3 months for those who received thrombectomy, compared with those who did not. Patients receiving the procedure had significantly improved clinical outcomes (odds ratio [OR], 3.76). The procedure is the standard of care for adults with large vessel occlusion (LVO) stroke, but limited data exist for children.
“In the absence of a randomized trial, this case-control study demonstrates better clinical outcomes with thrombectomy than medical management for pediatric patients aged 2 to 18 years with anterior circulation LVO stroke,” the authors concluded. The study was published in JAMA Neurology.
Improved results
Untreated LVO stroke is associated with poor outcomes, indicated in this study with scoring based on the modified Rankin Scale. Based on this scoring, 53.8% of patients who were managed conservatively had poor outcomes (moderate disability or greater) at 3 months, confirming previous findings. The data were drawn from five hospitals in Australia and Canada between January 2011 and April 2022.
Removing blood clots with mechanical thrombectomy resulted in improved outcomes 3 months after stroke for the patients included in the study, compared with the neuroprotective measures of medical therapy alone. The improved outcomes persisted in the final available follow-up (OR, 3.65).
In adults, thrombectomy has previously been demonstrated to be a safe and effective treatment for LVO stroke and is currently the standard of care. This study sought to expand the data for pediatric patients, for whom stroke is rarer and difficult to diagnose.
The authors cautioned, however, that the outcomes are from hospitals with pediatric neurology expertise and should not be generalized to settings without specialists.
Case-control study
While previous population-based studies of children with LVO stroke found that conservative treatment was associated with poor outcomes, these studies may include significant selection bias. The investigators chose to conduct the case-control study as an alternative to a randomized control trial, which would require withholding treatment from some patients and would not be considered ethical.
The study included 26 patients in each cohort, either receiving mechanical thrombectomy or medical treatment alone. The investigators matched patients by site and side of occlusion, age, and sex. Cases that could not be matched by site of occlusion, the primary criterion, were excluded.
With this methodology, the investigators reduced the impact of selection bias with the aim of providing “the next highest level of comparative evidence,” they stated in the study. However, they also noted that, without randomization, there is likely still some selection bias present.
The two cohorts were not significantly different based on factors such as sex or age. All patients in the study presented within 24 hours of symptom onset, with most eligible for thrombectomy by adult standards. There was a difference between the two cohorts in the timing of arrival to a dedicated hospital and imaging. “Our triage, imaging, and decision-making pathways require streamlining,” the authors concluded, regarding the difference.
‘A heterogeneous condition’
In a comment, Ratika Srivastava, MD, a pediatric neurologist at the University of Alberta, Edmonton, said she was glad to see a well-designed study dedicated to pediatric stroke. Neurologists have traditionally extrapolated from research on adult stroke due to the rarity of pediatric stroke and difficulty of diagnosis.
While physicians have previously relied on findings in adults, stroke presents differently in children. “The challenge is that it’s such a heterogeneous condition,” said Dr. Srivastava, who was not involved in the study. In children, stroke may have several different etiologies, such as a lesion in the heart or arterial disease. “Sometimes it’s amenable to taking the clot out and sometimes it’s not. So you have to figure out: Are they a good candidate for thrombectomy?” This study helps demonstrate that thrombectomy is a good option for some children with LVO stroke, she said.
The study was independently supported. Dr. Srivastava reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A matched case-control study followed 52 patients in Canada and Australia with acute stroke and assessed functional outcomes at 3 months for those who received thrombectomy, compared with those who did not. Patients receiving the procedure had significantly improved clinical outcomes (odds ratio [OR], 3.76). The procedure is the standard of care for adults with large vessel occlusion (LVO) stroke, but limited data exist for children.
“In the absence of a randomized trial, this case-control study demonstrates better clinical outcomes with thrombectomy than medical management for pediatric patients aged 2 to 18 years with anterior circulation LVO stroke,” the authors concluded. The study was published in JAMA Neurology.
Improved results
Untreated LVO stroke is associated with poor outcomes, indicated in this study with scoring based on the modified Rankin Scale. Based on this scoring, 53.8% of patients who were managed conservatively had poor outcomes (moderate disability or greater) at 3 months, confirming previous findings. The data were drawn from five hospitals in Australia and Canada between January 2011 and April 2022.
Removing blood clots with mechanical thrombectomy resulted in improved outcomes 3 months after stroke for the patients included in the study, compared with the neuroprotective measures of medical therapy alone. The improved outcomes persisted in the final available follow-up (OR, 3.65).
In adults, thrombectomy has previously been demonstrated to be a safe and effective treatment for LVO stroke and is currently the standard of care. This study sought to expand the data for pediatric patients, for whom stroke is rarer and difficult to diagnose.
The authors cautioned, however, that the outcomes are from hospitals with pediatric neurology expertise and should not be generalized to settings without specialists.
Case-control study
While previous population-based studies of children with LVO stroke found that conservative treatment was associated with poor outcomes, these studies may include significant selection bias. The investigators chose to conduct the case-control study as an alternative to a randomized control trial, which would require withholding treatment from some patients and would not be considered ethical.
The study included 26 patients in each cohort, either receiving mechanical thrombectomy or medical treatment alone. The investigators matched patients by site and side of occlusion, age, and sex. Cases that could not be matched by site of occlusion, the primary criterion, were excluded.
With this methodology, the investigators reduced the impact of selection bias with the aim of providing “the next highest level of comparative evidence,” they stated in the study. However, they also noted that, without randomization, there is likely still some selection bias present.
The two cohorts were not significantly different based on factors such as sex or age. All patients in the study presented within 24 hours of symptom onset, with most eligible for thrombectomy by adult standards. There was a difference between the two cohorts in the timing of arrival to a dedicated hospital and imaging. “Our triage, imaging, and decision-making pathways require streamlining,” the authors concluded, regarding the difference.
‘A heterogeneous condition’
In a comment, Ratika Srivastava, MD, a pediatric neurologist at the University of Alberta, Edmonton, said she was glad to see a well-designed study dedicated to pediatric stroke. Neurologists have traditionally extrapolated from research on adult stroke due to the rarity of pediatric stroke and difficulty of diagnosis.
While physicians have previously relied on findings in adults, stroke presents differently in children. “The challenge is that it’s such a heterogeneous condition,” said Dr. Srivastava, who was not involved in the study. In children, stroke may have several different etiologies, such as a lesion in the heart or arterial disease. “Sometimes it’s amenable to taking the clot out and sometimes it’s not. So you have to figure out: Are they a good candidate for thrombectomy?” This study helps demonstrate that thrombectomy is a good option for some children with LVO stroke, she said.
The study was independently supported. Dr. Srivastava reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY
OxyContin marketing push still exacting a deadly toll, study says
The uptick in rates of infectious diseases, namely, hepatitis and infective endocarditis, occurred after 2010, when OxyContin maker Purdue Pharma reformulated OxyContin to make it harder to crush and snort. This led many people who were already addicted to the powerful pain pills to move on to injecting heroin or fentanyl, which fueled the spread of infectious disease.
“Our results suggest that the mortality and morbidity consequences of OxyContin marketing continue to be salient more than 25 years later,” write Julia Dennett, PhD, and Gregg Gonsalves, PhD, with Yale University School of Public Health, New Haven, Conn.
Their study was published online in Health Affairs.
Long-term effects revealed
Until now, the long-term effects of widespread OxyContin marketing with regard to complications of injection drug use were unknown.
Dr. Dennett and Dr. Gonsalves evaluated the effects of OxyContin marketing on the long-term trajectories of various injection drug use–related outcomes. Using a difference-in-difference analysis, they compared states with high vs. low exposure to OxyContin marketing before and after the 2010 reformulation of the drug.
Before 2010, rates of infections associated with injection drug use and overdose deaths were similar in high- and low-marketing states, they found.
Those rates diverged after the 2010 reformulation, with more infections related to injection drug use in states exposed to more marketing.
Specifically, from 2010 until 2020, high-exposure states saw, on average, an additional 0.85 acute hepatitis B cases, 0.83 hepatitis C cases, and 0.62 cases of death from infective endocarditis per 100,000 residents.
High-exposure states also had 5.3 more deaths per 100,000 residents from synthetic opioid overdose.
“Prior to 2010, among these states, there were generally no statistically significant differences in these outcomes. After 2010, you saw them diverge dramatically,” Dr. Dennett said in a news release.
Dr. Dennett and Dr. Gonsalves say their findings support the view that the opioid epidemic is creating a converging public health crisis, as it is fueling a surge in infectious diseases, particularly hepatitis, infective endocarditis, and HIV.
“This study highlights a critical need for actions to address the spread of viral and bacterial infections and overdose associated with injection drug use, both in the states that were subject to Purdue’s promotional campaign and across the U.S. more broadly,” they add.
Purdue Pharma did not provide a comment on the study.
Funding for the study was provided by the National Institute on Drug Abuse. Disclosures for Dr. Dennett and Dr. Gonsalves were not available.
A version of this article first appeared on Medscape.com.
The uptick in rates of infectious diseases, namely, hepatitis and infective endocarditis, occurred after 2010, when OxyContin maker Purdue Pharma reformulated OxyContin to make it harder to crush and snort. This led many people who were already addicted to the powerful pain pills to move on to injecting heroin or fentanyl, which fueled the spread of infectious disease.
“Our results suggest that the mortality and morbidity consequences of OxyContin marketing continue to be salient more than 25 years later,” write Julia Dennett, PhD, and Gregg Gonsalves, PhD, with Yale University School of Public Health, New Haven, Conn.
Their study was published online in Health Affairs.
Long-term effects revealed
Until now, the long-term effects of widespread OxyContin marketing with regard to complications of injection drug use were unknown.
Dr. Dennett and Dr. Gonsalves evaluated the effects of OxyContin marketing on the long-term trajectories of various injection drug use–related outcomes. Using a difference-in-difference analysis, they compared states with high vs. low exposure to OxyContin marketing before and after the 2010 reformulation of the drug.
Before 2010, rates of infections associated with injection drug use and overdose deaths were similar in high- and low-marketing states, they found.
Those rates diverged after the 2010 reformulation, with more infections related to injection drug use in states exposed to more marketing.
Specifically, from 2010 until 2020, high-exposure states saw, on average, an additional 0.85 acute hepatitis B cases, 0.83 hepatitis C cases, and 0.62 cases of death from infective endocarditis per 100,000 residents.
High-exposure states also had 5.3 more deaths per 100,000 residents from synthetic opioid overdose.
“Prior to 2010, among these states, there were generally no statistically significant differences in these outcomes. After 2010, you saw them diverge dramatically,” Dr. Dennett said in a news release.
Dr. Dennett and Dr. Gonsalves say their findings support the view that the opioid epidemic is creating a converging public health crisis, as it is fueling a surge in infectious diseases, particularly hepatitis, infective endocarditis, and HIV.
“This study highlights a critical need for actions to address the spread of viral and bacterial infections and overdose associated with injection drug use, both in the states that were subject to Purdue’s promotional campaign and across the U.S. more broadly,” they add.
Purdue Pharma did not provide a comment on the study.
Funding for the study was provided by the National Institute on Drug Abuse. Disclosures for Dr. Dennett and Dr. Gonsalves were not available.
A version of this article first appeared on Medscape.com.
The uptick in rates of infectious diseases, namely, hepatitis and infective endocarditis, occurred after 2010, when OxyContin maker Purdue Pharma reformulated OxyContin to make it harder to crush and snort. This led many people who were already addicted to the powerful pain pills to move on to injecting heroin or fentanyl, which fueled the spread of infectious disease.
“Our results suggest that the mortality and morbidity consequences of OxyContin marketing continue to be salient more than 25 years later,” write Julia Dennett, PhD, and Gregg Gonsalves, PhD, with Yale University School of Public Health, New Haven, Conn.
Their study was published online in Health Affairs.
Long-term effects revealed
Until now, the long-term effects of widespread OxyContin marketing with regard to complications of injection drug use were unknown.
Dr. Dennett and Dr. Gonsalves evaluated the effects of OxyContin marketing on the long-term trajectories of various injection drug use–related outcomes. Using a difference-in-difference analysis, they compared states with high vs. low exposure to OxyContin marketing before and after the 2010 reformulation of the drug.
Before 2010, rates of infections associated with injection drug use and overdose deaths were similar in high- and low-marketing states, they found.
Those rates diverged after the 2010 reformulation, with more infections related to injection drug use in states exposed to more marketing.
Specifically, from 2010 until 2020, high-exposure states saw, on average, an additional 0.85 acute hepatitis B cases, 0.83 hepatitis C cases, and 0.62 cases of death from infective endocarditis per 100,000 residents.
High-exposure states also had 5.3 more deaths per 100,000 residents from synthetic opioid overdose.
“Prior to 2010, among these states, there were generally no statistically significant differences in these outcomes. After 2010, you saw them diverge dramatically,” Dr. Dennett said in a news release.
Dr. Dennett and Dr. Gonsalves say their findings support the view that the opioid epidemic is creating a converging public health crisis, as it is fueling a surge in infectious diseases, particularly hepatitis, infective endocarditis, and HIV.
“This study highlights a critical need for actions to address the spread of viral and bacterial infections and overdose associated with injection drug use, both in the states that were subject to Purdue’s promotional campaign and across the U.S. more broadly,” they add.
Purdue Pharma did not provide a comment on the study.
Funding for the study was provided by the National Institute on Drug Abuse. Disclosures for Dr. Dennett and Dr. Gonsalves were not available.
A version of this article first appeared on Medscape.com.
FROM HEALTH AFFAIRS
Cigna accused of using AI, not doctors, to deny claims: Lawsuit
and forcing providers to bill patients in full.
In a complaint filed recently in California’s eastern district court, plaintiffs and Cigna health plan members Suzanne Kisting-Leung and Ayesha Smiley and their attorneys say that Cigna violates state insurance regulations by failing to conduct a “thorough, fair, and objective” review of their and other members’ claims.
The lawsuit says that, instead, Cigna relies on an algorithm, PxDx, to review and frequently deny medically necessary claims. According to court records, the system allows Cigna’s doctors to “instantly reject claims on medical grounds without ever opening patient files.” With use of the system, the average claims processing time is 1.2 seconds.
Cigna says it uses technology to verify coding on standard, low-cost procedures and to expedite physician reimbursement. In a statement to CBS News, the company called the lawsuit “highly questionable.”
The case highlights growing concerns about AI and its ability to replace humans for tasks and interactions in health care, business, and beyond. Public advocacy law firm Clarkson, which is representing the plaintiffs, has previously sued tech giants Google and ChatGPT creator OpenAI for harvesting Internet users’ personal and professional data to train their AI systems.
According to the complaint, Cigna denied the plaintiffs medically necessary tests, including blood work to screen for vitamin D deficiency and ultrasounds for patients suspected of having ovarian cancer. The plaintiffs’ attempts to appeal were unfruitful, and they were forced to pay out of pocket.
The plaintiff’s attorneys argue that the claims do not undergo more detailed reviews by physicians and employees, as mandated by California insurance laws, and that Cigna benefits by saving on labor costs.
Clarkson is demanding a jury trial and has asked the court to certify the Cigna case as a federal class action, potentially allowing the insurer’s other 2 million health plan members in California to join the lawsuit.
I. Glenn Cohen, JD, deputy dean and professor at Harvard Law School, Cambridge, Mass., said in an interview that this is the first lawsuit he’s aware of in which AI was involved in denying health insurance claims and that it is probably an uphill battle for the plaintiffs.
“In the last 25 years, the U.S. Supreme Court’s decisions have made getting a class action approved more difficult. If allowed to go forward as a class action, which Cigna is likely to vigorously oppose, then the pressure on Cigna to settle the case becomes enormous,” he said.
The allegations come after a recent deep dive by the nonprofit ProPublica uncovered similar claim denial issues. One physician who worked for Cigna told the nonprofit that he and other company doctors essentially rubber-stamped the denials in batches, which took “all of 10 seconds to do 50 at a time.”
In 2022, the American Medical Association and two state physician groups joined another class action against Cigna stemming from allegations that the insurer’s intermediary, Multiplan, intentionally underpaid medical claims. And in March, Cigna’s pharmacy benefit manager, Express Scripts, was accused of conspiring with other PBMs to drive up prescription drug prices for Ohio consumers, violating state antitrust laws.
Mr. Cohen said he expects Cigna to push back in court about the California class size, which the plaintiff’s attorneys hope will encompass all Cigna health plan members in the state.
“The injury is primarily to those whose claims were denied by AI, presumably a much smaller set of individuals and harder to identify,” said Mr. Cohen.
A version of this article first appeared on Medscape.com.
and forcing providers to bill patients in full.
In a complaint filed recently in California’s eastern district court, plaintiffs and Cigna health plan members Suzanne Kisting-Leung and Ayesha Smiley and their attorneys say that Cigna violates state insurance regulations by failing to conduct a “thorough, fair, and objective” review of their and other members’ claims.
The lawsuit says that, instead, Cigna relies on an algorithm, PxDx, to review and frequently deny medically necessary claims. According to court records, the system allows Cigna’s doctors to “instantly reject claims on medical grounds without ever opening patient files.” With use of the system, the average claims processing time is 1.2 seconds.
Cigna says it uses technology to verify coding on standard, low-cost procedures and to expedite physician reimbursement. In a statement to CBS News, the company called the lawsuit “highly questionable.”
The case highlights growing concerns about AI and its ability to replace humans for tasks and interactions in health care, business, and beyond. Public advocacy law firm Clarkson, which is representing the plaintiffs, has previously sued tech giants Google and ChatGPT creator OpenAI for harvesting Internet users’ personal and professional data to train their AI systems.
According to the complaint, Cigna denied the plaintiffs medically necessary tests, including blood work to screen for vitamin D deficiency and ultrasounds for patients suspected of having ovarian cancer. The plaintiffs’ attempts to appeal were unfruitful, and they were forced to pay out of pocket.
The plaintiff’s attorneys argue that the claims do not undergo more detailed reviews by physicians and employees, as mandated by California insurance laws, and that Cigna benefits by saving on labor costs.
Clarkson is demanding a jury trial and has asked the court to certify the Cigna case as a federal class action, potentially allowing the insurer’s other 2 million health plan members in California to join the lawsuit.
I. Glenn Cohen, JD, deputy dean and professor at Harvard Law School, Cambridge, Mass., said in an interview that this is the first lawsuit he’s aware of in which AI was involved in denying health insurance claims and that it is probably an uphill battle for the plaintiffs.
“In the last 25 years, the U.S. Supreme Court’s decisions have made getting a class action approved more difficult. If allowed to go forward as a class action, which Cigna is likely to vigorously oppose, then the pressure on Cigna to settle the case becomes enormous,” he said.
The allegations come after a recent deep dive by the nonprofit ProPublica uncovered similar claim denial issues. One physician who worked for Cigna told the nonprofit that he and other company doctors essentially rubber-stamped the denials in batches, which took “all of 10 seconds to do 50 at a time.”
In 2022, the American Medical Association and two state physician groups joined another class action against Cigna stemming from allegations that the insurer’s intermediary, Multiplan, intentionally underpaid medical claims. And in March, Cigna’s pharmacy benefit manager, Express Scripts, was accused of conspiring with other PBMs to drive up prescription drug prices for Ohio consumers, violating state antitrust laws.
Mr. Cohen said he expects Cigna to push back in court about the California class size, which the plaintiff’s attorneys hope will encompass all Cigna health plan members in the state.
“The injury is primarily to those whose claims were denied by AI, presumably a much smaller set of individuals and harder to identify,” said Mr. Cohen.
A version of this article first appeared on Medscape.com.
and forcing providers to bill patients in full.
In a complaint filed recently in California’s eastern district court, plaintiffs and Cigna health plan members Suzanne Kisting-Leung and Ayesha Smiley and their attorneys say that Cigna violates state insurance regulations by failing to conduct a “thorough, fair, and objective” review of their and other members’ claims.
The lawsuit says that, instead, Cigna relies on an algorithm, PxDx, to review and frequently deny medically necessary claims. According to court records, the system allows Cigna’s doctors to “instantly reject claims on medical grounds without ever opening patient files.” With use of the system, the average claims processing time is 1.2 seconds.
Cigna says it uses technology to verify coding on standard, low-cost procedures and to expedite physician reimbursement. In a statement to CBS News, the company called the lawsuit “highly questionable.”
The case highlights growing concerns about AI and its ability to replace humans for tasks and interactions in health care, business, and beyond. Public advocacy law firm Clarkson, which is representing the plaintiffs, has previously sued tech giants Google and ChatGPT creator OpenAI for harvesting Internet users’ personal and professional data to train their AI systems.
According to the complaint, Cigna denied the plaintiffs medically necessary tests, including blood work to screen for vitamin D deficiency and ultrasounds for patients suspected of having ovarian cancer. The plaintiffs’ attempts to appeal were unfruitful, and they were forced to pay out of pocket.
The plaintiff’s attorneys argue that the claims do not undergo more detailed reviews by physicians and employees, as mandated by California insurance laws, and that Cigna benefits by saving on labor costs.
Clarkson is demanding a jury trial and has asked the court to certify the Cigna case as a federal class action, potentially allowing the insurer’s other 2 million health plan members in California to join the lawsuit.
I. Glenn Cohen, JD, deputy dean and professor at Harvard Law School, Cambridge, Mass., said in an interview that this is the first lawsuit he’s aware of in which AI was involved in denying health insurance claims and that it is probably an uphill battle for the plaintiffs.
“In the last 25 years, the U.S. Supreme Court’s decisions have made getting a class action approved more difficult. If allowed to go forward as a class action, which Cigna is likely to vigorously oppose, then the pressure on Cigna to settle the case becomes enormous,” he said.
The allegations come after a recent deep dive by the nonprofit ProPublica uncovered similar claim denial issues. One physician who worked for Cigna told the nonprofit that he and other company doctors essentially rubber-stamped the denials in batches, which took “all of 10 seconds to do 50 at a time.”
In 2022, the American Medical Association and two state physician groups joined another class action against Cigna stemming from allegations that the insurer’s intermediary, Multiplan, intentionally underpaid medical claims. And in March, Cigna’s pharmacy benefit manager, Express Scripts, was accused of conspiring with other PBMs to drive up prescription drug prices for Ohio consumers, violating state antitrust laws.
Mr. Cohen said he expects Cigna to push back in court about the California class size, which the plaintiff’s attorneys hope will encompass all Cigna health plan members in the state.
“The injury is primarily to those whose claims were denied by AI, presumably a much smaller set of individuals and harder to identify,” said Mr. Cohen.
A version of this article first appeared on Medscape.com.
Black women weigh emerging risks of ‘creamy crack’ hair straighteners
Deanna Denham Hughes was stunned when she was diagnosed with ovarian cancer in 2022. She was only 32. She had no family history of cancer, and tests found no genetic link. Ms. Hughes wondered why she, an otherwise healthy Black mother of two, would develop a malignancy known as a “silent killer.”
After emergency surgery to remove the mass, along with her ovaries, uterus, fallopian tubes, and appendix, Ms. Hughes said, she saw an Instagram post in which a woman with uterine cancer linked her condition to chemical hair straighteners.
“I almost fell over,” she said from her home in Smyrna, Ga.
When Ms. Hughes was about 4, her mother began applying a chemical straightener, or relaxer, to her hair every 6-8 weeks. “It burned, and it smelled awful,” Ms. Hughes recalled. “But it was just part of our routine to ‘deal with my hair.’ ”
The routine continued until she went to college and met other Black women who wore their hair naturally. Soon, Ms. Hughes quit relaxers.
Social and economic pressures have long compelled Black girls and women to straighten their hair to conform to Eurocentric beauty standards. But chemical straighteners are stinky and costly and sometimes cause painful scalp burns. Mounting evidence now shows they could be a health hazard.
Relaxers can contain carcinogens, such as formaldehyde-releasing agents, phthalates, and other endocrine-disrupting compounds, according to National Institutes of Health studies. The compounds can mimic the body’s hormones and have been linked to breast, uterine, and ovarian cancers, studies show.
African American women’s often frequent and lifelong application of chemical relaxers to their hair and scalp might explain why hormone-related cancers kill disproportionately more Black than White women, say researchers and cancer doctors.
“What’s in these products is harmful,” said Tamarra James-Todd, PhD, an epidemiology professor at Harvard T.H. Chan School of Public Health, Boston, who has studied straightening products for the past 20 years.
She believes manufacturers, policymakers, and physicians should warn consumers that relaxers might cause cancer and other health problems.
But regulators have been slow to act, physicians have been reluctant to take up the cause, and racism continues to dictate fashion standards that make it tough for women to quit relaxers, products so addictive they’re known as “creamy crack.”
Michelle Obama straightened her hair when Barack Obama served as president because she believed Americans were “not ready” to see her in braids, the former first lady said after leaving the White House. The U.S. military still prohibited popular Black hairstyles such as dreadlocks and twists while the nation’s first Black president was in office.
California in 2019 became the first of nearly two dozen states to ban race-based hair discrimination. Last year, the U.S. House of Representatives passed similar legislation, known as the CROWN Act, for Creating a Respectful and Open World for Natural Hair. But the bill failed in the Senate.
The need for legislation underscores the challenges Black girls and women face at school and in the workplace.
“You have to pick your struggles,” said Atlanta-based surgical oncologist Ryland J. Gore, MD. She informs her breast cancer patients about the increased cancer risk from relaxers. Despite her knowledge, however, Dr. Gore continues to use chemical straighteners on her own hair, as she has since she was about 7 years old.
“Your hair tells a story,” she said.
In conversations with patients, Dr. Gore sometimes talks about how African American women once wove messages into their braids about the route to take on the Underground Railroad as they sought freedom from slavery.
“It’s just a deep discussion,” one that touches on culture, history, and research into current hairstyling practices, she said. “The data is out there. So patients should be warned, and then they can make a decision.”
The first hint of a connection between hair products and health issues surfaced in the 1990s. Doctors began seeing signs of sexual maturation in Black babies and young girls who developed breasts and pubic hair after using shampoo containing estrogen or placental extract. When the girls stopped using the shampoo, the hair and breast development receded, according to a study published in the journal Clinical Pediatrics in 1998.
Since then, Dr. James-Todd and other researchers have linked chemicals in hair products to a variety of health issues more prevalent among Black women – from early puberty to preterm birth, obesity, and diabetes.
In recent years, researchers have focused on a possible connection between ingredients in chemical relaxers and hormone-related cancers, like the one Ms. Hughes developed, which tend to be more aggressive and deadly in Black women.
A 2017 study found White women who used chemical relaxers were nearly twice as likely to develop breast cancer as those who did not use them. Because the vast majority of the Black study participants used relaxers, researchers could not effectively test the association in Black women, said lead author Adana Llanos, PhD, associate professor of epidemiology at Columbia University’s Mailman School of Public Health, New York.
Researchers did test it in 2020.
The so-called Sister Study, a landmark National Institute of Environmental Health Sciences investigation into the causes of breast cancer and related diseases, followed 50,000 U.S. women whose sisters had been diagnosed with breast cancer and who were cancer-free when they enrolled. Regardless of race, women who reported using relaxers in the prior year were 18% more likely to be diagnosed with breast cancer. Those who used relaxers at least every 5-8 weeks had a 31% higher breast cancer risk.
Nearly 75% of the Black sisters used relaxers in the prior year, compared with 3% of the non-Hispanic White sisters. Three-quarters of Black women self-reported using the straighteners as adolescents, and frequent use of chemical straighteners during adolescence raised the risk of premenopausal breast cancer, a 2021 NIH-funded study in the International Journal of Cancer found.
Another 2021 analysis of the Sister Study data showed sisters who self-reported that they frequently used relaxers or pressing products doubled their ovarian cancer risk. In 2022, another study found frequent use more than doubled uterine cancer risk.
After researchers discovered the link with uterine cancer, some called for policy changes and other measures to reduce exposure to chemical relaxers.
“It is time to intervene,” Dr. Llanos and her colleagues wrote in a Journal of the National Cancer Institute editorial accompanying the uterine cancer analysis. While acknowledging the need for more research, they issued a “call for action.”
No one can say that using permanent hair straighteners will give you cancer, Dr. Llanos said in an interview. “That’s not how cancer works,” she said, noting that some smokers never develop lung cancer, despite tobacco use being a known risk factor.
The body of research linking hair straighteners and cancer is more limited, said Dr. Llanos, who quit using chemical relaxers 15 years ago. But, she asked rhetorically, “Do we need to do the research for 50 more years to know that chemical relaxers are harmful?”
Charlotte R. Gamble, MD, a gynecological oncologist whose Washington, D.C., practice includes Black women with uterine and ovarian cancer, said she and her colleagues see the uterine cancer study findings as worthy of further exploration – but not yet worthy of discussion with patients.
“The jury’s out for me personally,” she said. “There’s so much more data that’s needed.”
Meanwhile, Dr. James-Todd and other researchers believe they have built a solid body of evidence.
“There are enough things we do know to begin taking action, developing interventions, providing useful information to clinicians and patients and the general public,” said Traci N. Bethea, PhD, assistant professor in the Office of Minority Health and Health Disparities Research at Georgetown University.
Responsibility for regulating personal-care products, including chemical hair straighteners and hair dyes – which also have been linked to hormone-related cancers – lies with the Food and Drug Administration. But the FDA does not subject personal-care products to the same approval process it uses for food and drugs. The FDA restricts only 11 categories of chemicals used in cosmetics, while concerns about health effects have prompted the European Union to restrict the use of at least 2,400 substances.
In March, Reps. Ayanna Pressley (D-Mass.) and Shontel Brown (D-Ohio) asked the FDA to investigate the potential health threat posed by chemical relaxers. An FDA representative said the agency would look into it.
Natural hairstyles are enjoying a resurgence among Black girls and women, but many continue to rely on the creamy crack, said Dede Teteh, DrPH, assistant professor of public health at Chapman University, Irvine, Calif.
She had her first straightening perm at 8 and has struggled to withdraw from relaxers as an adult, said Dr. Teteh, who now wears locs. Not long ago, she considered chemically straightening her hair for an academic job interview because she didn’t want her hair to “be a hindrance” when she appeared before White professors.
Dr. Teteh led “The Cost of Beauty,” a hair-health research project published in 2017. She and her team interviewed 91 Black women in Southern California. Some became “combative” at the idea of quitting relaxers and claimed “everything can cause cancer.”
Their reactions speak to the challenges Black women face in America, Dr. Teteh said.
“It’s not that people do not want to hear the information related to their health,” she said. “But they want people to share the information in a way that it’s really empathetic to the plight of being Black here in the United States.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.
Deanna Denham Hughes was stunned when she was diagnosed with ovarian cancer in 2022. She was only 32. She had no family history of cancer, and tests found no genetic link. Ms. Hughes wondered why she, an otherwise healthy Black mother of two, would develop a malignancy known as a “silent killer.”
After emergency surgery to remove the mass, along with her ovaries, uterus, fallopian tubes, and appendix, Ms. Hughes said, she saw an Instagram post in which a woman with uterine cancer linked her condition to chemical hair straighteners.
“I almost fell over,” she said from her home in Smyrna, Ga.
When Ms. Hughes was about 4, her mother began applying a chemical straightener, or relaxer, to her hair every 6-8 weeks. “It burned, and it smelled awful,” Ms. Hughes recalled. “But it was just part of our routine to ‘deal with my hair.’ ”
The routine continued until she went to college and met other Black women who wore their hair naturally. Soon, Ms. Hughes quit relaxers.
Social and economic pressures have long compelled Black girls and women to straighten their hair to conform to Eurocentric beauty standards. But chemical straighteners are stinky and costly and sometimes cause painful scalp burns. Mounting evidence now shows they could be a health hazard.
Relaxers can contain carcinogens, such as formaldehyde-releasing agents, phthalates, and other endocrine-disrupting compounds, according to National Institutes of Health studies. The compounds can mimic the body’s hormones and have been linked to breast, uterine, and ovarian cancers, studies show.
African American women’s often frequent and lifelong application of chemical relaxers to their hair and scalp might explain why hormone-related cancers kill disproportionately more Black than White women, say researchers and cancer doctors.
“What’s in these products is harmful,” said Tamarra James-Todd, PhD, an epidemiology professor at Harvard T.H. Chan School of Public Health, Boston, who has studied straightening products for the past 20 years.
She believes manufacturers, policymakers, and physicians should warn consumers that relaxers might cause cancer and other health problems.
But regulators have been slow to act, physicians have been reluctant to take up the cause, and racism continues to dictate fashion standards that make it tough for women to quit relaxers, products so addictive they’re known as “creamy crack.”
Michelle Obama straightened her hair when Barack Obama served as president because she believed Americans were “not ready” to see her in braids, the former first lady said after leaving the White House. The U.S. military still prohibited popular Black hairstyles such as dreadlocks and twists while the nation’s first Black president was in office.
California in 2019 became the first of nearly two dozen states to ban race-based hair discrimination. Last year, the U.S. House of Representatives passed similar legislation, known as the CROWN Act, for Creating a Respectful and Open World for Natural Hair. But the bill failed in the Senate.
The need for legislation underscores the challenges Black girls and women face at school and in the workplace.
“You have to pick your struggles,” said Atlanta-based surgical oncologist Ryland J. Gore, MD. She informs her breast cancer patients about the increased cancer risk from relaxers. Despite her knowledge, however, Dr. Gore continues to use chemical straighteners on her own hair, as she has since she was about 7 years old.
“Your hair tells a story,” she said.
In conversations with patients, Dr. Gore sometimes talks about how African American women once wove messages into their braids about the route to take on the Underground Railroad as they sought freedom from slavery.
“It’s just a deep discussion,” one that touches on culture, history, and research into current hairstyling practices, she said. “The data is out there. So patients should be warned, and then they can make a decision.”
The first hint of a connection between hair products and health issues surfaced in the 1990s. Doctors began seeing signs of sexual maturation in Black babies and young girls who developed breasts and pubic hair after using shampoo containing estrogen or placental extract. When the girls stopped using the shampoo, the hair and breast development receded, according to a study published in the journal Clinical Pediatrics in 1998.
Since then, Dr. James-Todd and other researchers have linked chemicals in hair products to a variety of health issues more prevalent among Black women – from early puberty to preterm birth, obesity, and diabetes.
In recent years, researchers have focused on a possible connection between ingredients in chemical relaxers and hormone-related cancers, like the one Ms. Hughes developed, which tend to be more aggressive and deadly in Black women.
A 2017 study found White women who used chemical relaxers were nearly twice as likely to develop breast cancer as those who did not use them. Because the vast majority of the Black study participants used relaxers, researchers could not effectively test the association in Black women, said lead author Adana Llanos, PhD, associate professor of epidemiology at Columbia University’s Mailman School of Public Health, New York.
Researchers did test it in 2020.
The so-called Sister Study, a landmark National Institute of Environmental Health Sciences investigation into the causes of breast cancer and related diseases, followed 50,000 U.S. women whose sisters had been diagnosed with breast cancer and who were cancer-free when they enrolled. Regardless of race, women who reported using relaxers in the prior year were 18% more likely to be diagnosed with breast cancer. Those who used relaxers at least every 5-8 weeks had a 31% higher breast cancer risk.
Nearly 75% of the Black sisters used relaxers in the prior year, compared with 3% of the non-Hispanic White sisters. Three-quarters of Black women self-reported using the straighteners as adolescents, and frequent use of chemical straighteners during adolescence raised the risk of premenopausal breast cancer, a 2021 NIH-funded study in the International Journal of Cancer found.
Another 2021 analysis of the Sister Study data showed sisters who self-reported that they frequently used relaxers or pressing products doubled their ovarian cancer risk. In 2022, another study found frequent use more than doubled uterine cancer risk.
After researchers discovered the link with uterine cancer, some called for policy changes and other measures to reduce exposure to chemical relaxers.
“It is time to intervene,” Dr. Llanos and her colleagues wrote in a Journal of the National Cancer Institute editorial accompanying the uterine cancer analysis. While acknowledging the need for more research, they issued a “call for action.”
No one can say that using permanent hair straighteners will give you cancer, Dr. Llanos said in an interview. “That’s not how cancer works,” she said, noting that some smokers never develop lung cancer, despite tobacco use being a known risk factor.
The body of research linking hair straighteners and cancer is more limited, said Dr. Llanos, who quit using chemical relaxers 15 years ago. But, she asked rhetorically, “Do we need to do the research for 50 more years to know that chemical relaxers are harmful?”
Charlotte R. Gamble, MD, a gynecological oncologist whose Washington, D.C., practice includes Black women with uterine and ovarian cancer, said she and her colleagues see the uterine cancer study findings as worthy of further exploration – but not yet worthy of discussion with patients.
“The jury’s out for me personally,” she said. “There’s so much more data that’s needed.”
Meanwhile, Dr. James-Todd and other researchers believe they have built a solid body of evidence.
“There are enough things we do know to begin taking action, developing interventions, providing useful information to clinicians and patients and the general public,” said Traci N. Bethea, PhD, assistant professor in the Office of Minority Health and Health Disparities Research at Georgetown University.
Responsibility for regulating personal-care products, including chemical hair straighteners and hair dyes – which also have been linked to hormone-related cancers – lies with the Food and Drug Administration. But the FDA does not subject personal-care products to the same approval process it uses for food and drugs. The FDA restricts only 11 categories of chemicals used in cosmetics, while concerns about health effects have prompted the European Union to restrict the use of at least 2,400 substances.
In March, Reps. Ayanna Pressley (D-Mass.) and Shontel Brown (D-Ohio) asked the FDA to investigate the potential health threat posed by chemical relaxers. An FDA representative said the agency would look into it.
Natural hairstyles are enjoying a resurgence among Black girls and women, but many continue to rely on the creamy crack, said Dede Teteh, DrPH, assistant professor of public health at Chapman University, Irvine, Calif.
She had her first straightening perm at 8 and has struggled to withdraw from relaxers as an adult, said Dr. Teteh, who now wears locs. Not long ago, she considered chemically straightening her hair for an academic job interview because she didn’t want her hair to “be a hindrance” when she appeared before White professors.
Dr. Teteh led “The Cost of Beauty,” a hair-health research project published in 2017. She and her team interviewed 91 Black women in Southern California. Some became “combative” at the idea of quitting relaxers and claimed “everything can cause cancer.”
Their reactions speak to the challenges Black women face in America, Dr. Teteh said.
“It’s not that people do not want to hear the information related to their health,” she said. “But they want people to share the information in a way that it’s really empathetic to the plight of being Black here in the United States.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.
Deanna Denham Hughes was stunned when she was diagnosed with ovarian cancer in 2022. She was only 32. She had no family history of cancer, and tests found no genetic link. Ms. Hughes wondered why she, an otherwise healthy Black mother of two, would develop a malignancy known as a “silent killer.”
After emergency surgery to remove the mass, along with her ovaries, uterus, fallopian tubes, and appendix, Ms. Hughes said, she saw an Instagram post in which a woman with uterine cancer linked her condition to chemical hair straighteners.
“I almost fell over,” she said from her home in Smyrna, Ga.
When Ms. Hughes was about 4, her mother began applying a chemical straightener, or relaxer, to her hair every 6-8 weeks. “It burned, and it smelled awful,” Ms. Hughes recalled. “But it was just part of our routine to ‘deal with my hair.’ ”
The routine continued until she went to college and met other Black women who wore their hair naturally. Soon, Ms. Hughes quit relaxers.
Social and economic pressures have long compelled Black girls and women to straighten their hair to conform to Eurocentric beauty standards. But chemical straighteners are stinky and costly and sometimes cause painful scalp burns. Mounting evidence now shows they could be a health hazard.
Relaxers can contain carcinogens, such as formaldehyde-releasing agents, phthalates, and other endocrine-disrupting compounds, according to National Institutes of Health studies. The compounds can mimic the body’s hormones and have been linked to breast, uterine, and ovarian cancers, studies show.
African American women’s often frequent and lifelong application of chemical relaxers to their hair and scalp might explain why hormone-related cancers kill disproportionately more Black than White women, say researchers and cancer doctors.
“What’s in these products is harmful,” said Tamarra James-Todd, PhD, an epidemiology professor at Harvard T.H. Chan School of Public Health, Boston, who has studied straightening products for the past 20 years.
She believes manufacturers, policymakers, and physicians should warn consumers that relaxers might cause cancer and other health problems.
But regulators have been slow to act, physicians have been reluctant to take up the cause, and racism continues to dictate fashion standards that make it tough for women to quit relaxers, products so addictive they’re known as “creamy crack.”
Michelle Obama straightened her hair when Barack Obama served as president because she believed Americans were “not ready” to see her in braids, the former first lady said after leaving the White House. The U.S. military still prohibited popular Black hairstyles such as dreadlocks and twists while the nation’s first Black president was in office.
California in 2019 became the first of nearly two dozen states to ban race-based hair discrimination. Last year, the U.S. House of Representatives passed similar legislation, known as the CROWN Act, for Creating a Respectful and Open World for Natural Hair. But the bill failed in the Senate.
The need for legislation underscores the challenges Black girls and women face at school and in the workplace.
“You have to pick your struggles,” said Atlanta-based surgical oncologist Ryland J. Gore, MD. She informs her breast cancer patients about the increased cancer risk from relaxers. Despite her knowledge, however, Dr. Gore continues to use chemical straighteners on her own hair, as she has since she was about 7 years old.
“Your hair tells a story,” she said.
In conversations with patients, Dr. Gore sometimes talks about how African American women once wove messages into their braids about the route to take on the Underground Railroad as they sought freedom from slavery.
“It’s just a deep discussion,” one that touches on culture, history, and research into current hairstyling practices, she said. “The data is out there. So patients should be warned, and then they can make a decision.”
The first hint of a connection between hair products and health issues surfaced in the 1990s. Doctors began seeing signs of sexual maturation in Black babies and young girls who developed breasts and pubic hair after using shampoo containing estrogen or placental extract. When the girls stopped using the shampoo, the hair and breast development receded, according to a study published in the journal Clinical Pediatrics in 1998.
Since then, Dr. James-Todd and other researchers have linked chemicals in hair products to a variety of health issues more prevalent among Black women – from early puberty to preterm birth, obesity, and diabetes.
In recent years, researchers have focused on a possible connection between ingredients in chemical relaxers and hormone-related cancers, like the one Ms. Hughes developed, which tend to be more aggressive and deadly in Black women.
A 2017 study found White women who used chemical relaxers were nearly twice as likely to develop breast cancer as those who did not use them. Because the vast majority of the Black study participants used relaxers, researchers could not effectively test the association in Black women, said lead author Adana Llanos, PhD, associate professor of epidemiology at Columbia University’s Mailman School of Public Health, New York.
Researchers did test it in 2020.
The so-called Sister Study, a landmark National Institute of Environmental Health Sciences investigation into the causes of breast cancer and related diseases, followed 50,000 U.S. women whose sisters had been diagnosed with breast cancer and who were cancer-free when they enrolled. Regardless of race, women who reported using relaxers in the prior year were 18% more likely to be diagnosed with breast cancer. Those who used relaxers at least every 5-8 weeks had a 31% higher breast cancer risk.
Nearly 75% of the Black sisters used relaxers in the prior year, compared with 3% of the non-Hispanic White sisters. Three-quarters of Black women self-reported using the straighteners as adolescents, and frequent use of chemical straighteners during adolescence raised the risk of premenopausal breast cancer, a 2021 NIH-funded study in the International Journal of Cancer found.
Another 2021 analysis of the Sister Study data showed sisters who self-reported that they frequently used relaxers or pressing products doubled their ovarian cancer risk. In 2022, another study found frequent use more than doubled uterine cancer risk.
After researchers discovered the link with uterine cancer, some called for policy changes and other measures to reduce exposure to chemical relaxers.
“It is time to intervene,” Dr. Llanos and her colleagues wrote in a Journal of the National Cancer Institute editorial accompanying the uterine cancer analysis. While acknowledging the need for more research, they issued a “call for action.”
No one can say that using permanent hair straighteners will give you cancer, Dr. Llanos said in an interview. “That’s not how cancer works,” she said, noting that some smokers never develop lung cancer, despite tobacco use being a known risk factor.
The body of research linking hair straighteners and cancer is more limited, said Dr. Llanos, who quit using chemical relaxers 15 years ago. But, she asked rhetorically, “Do we need to do the research for 50 more years to know that chemical relaxers are harmful?”
Charlotte R. Gamble, MD, a gynecological oncologist whose Washington, D.C., practice includes Black women with uterine and ovarian cancer, said she and her colleagues see the uterine cancer study findings as worthy of further exploration – but not yet worthy of discussion with patients.
“The jury’s out for me personally,” she said. “There’s so much more data that’s needed.”
Meanwhile, Dr. James-Todd and other researchers believe they have built a solid body of evidence.
“There are enough things we do know to begin taking action, developing interventions, providing useful information to clinicians and patients and the general public,” said Traci N. Bethea, PhD, assistant professor in the Office of Minority Health and Health Disparities Research at Georgetown University.
Responsibility for regulating personal-care products, including chemical hair straighteners and hair dyes – which also have been linked to hormone-related cancers – lies with the Food and Drug Administration. But the FDA does not subject personal-care products to the same approval process it uses for food and drugs. The FDA restricts only 11 categories of chemicals used in cosmetics, while concerns about health effects have prompted the European Union to restrict the use of at least 2,400 substances.
In March, Reps. Ayanna Pressley (D-Mass.) and Shontel Brown (D-Ohio) asked the FDA to investigate the potential health threat posed by chemical relaxers. An FDA representative said the agency would look into it.
Natural hairstyles are enjoying a resurgence among Black girls and women, but many continue to rely on the creamy crack, said Dede Teteh, DrPH, assistant professor of public health at Chapman University, Irvine, Calif.
She had her first straightening perm at 8 and has struggled to withdraw from relaxers as an adult, said Dr. Teteh, who now wears locs. Not long ago, she considered chemically straightening her hair for an academic job interview because she didn’t want her hair to “be a hindrance” when she appeared before White professors.
Dr. Teteh led “The Cost of Beauty,” a hair-health research project published in 2017. She and her team interviewed 91 Black women in Southern California. Some became “combative” at the idea of quitting relaxers and claimed “everything can cause cancer.”
Their reactions speak to the challenges Black women face in America, Dr. Teteh said.
“It’s not that people do not want to hear the information related to their health,” she said. “But they want people to share the information in a way that it’s really empathetic to the plight of being Black here in the United States.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.
FDA approves first pill for postpartum depression
a condition that affects an estimated one in seven mothers in the United States.
The pill, zuranolone (Zurzuvae), is a neuroactive steroid that acts on GABAA receptors in the brain responsible for regulating mood, arousal, behavior, and cognition, according to Biogen, which, along with Sage Therapeutics, developed the product. The recommended dose for Zurzuvae is 50 mg taken once daily for 14 days, in the evening with a fatty meal, according to the FDA.
Postpartum depression often goes undiagnosed and untreated. Many mothers are hesitant to reveal their symptoms to family and clinicians, fearing they’ll be judged on their parenting. A 2017 study found that suicide accounted for roughly 5% of perinatal deaths among women in Canada, with most of those deaths occurring in the first 3 months in the year after giving birth.
“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness – even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research, said in a statement about the approval. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”
The other approved therapy for postpartum depression is the intravenous agent brexanolone (Zulresso; Sage). But the product requires prolonged infusions in hospital settings and costs $34,000.
FDA approval of Zurzuvae was based in part on data reported in a 2023 study in the American Journal of Psychiatry, which showed that the drug led to significantly greater improvement in depressive symptoms at 15 days compared with the placebo group. Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).
Patients with anxiety who received the active drug experienced improvement in related symptoms compared with the patients who received a placebo.
The most common adverse events reported in the trial were somnolence and headaches. Weight gain, sexual dysfunction, withdrawal symptoms, and increased suicidal ideation or behavior were not observed.
The packaging for Zurzuvae will include a boxed warning noting that the drug can affect a user’s ability to drive and perform other potentially hazardous activities, possibly without their knowledge of the impairment, the FDA said. As a result, people who use Zurzuvae should not drive or operate heavy machinery for at least 12 hours after taking the pill.
A version of this article first appeared on Medscape.com.
a condition that affects an estimated one in seven mothers in the United States.
The pill, zuranolone (Zurzuvae), is a neuroactive steroid that acts on GABAA receptors in the brain responsible for regulating mood, arousal, behavior, and cognition, according to Biogen, which, along with Sage Therapeutics, developed the product. The recommended dose for Zurzuvae is 50 mg taken once daily for 14 days, in the evening with a fatty meal, according to the FDA.
Postpartum depression often goes undiagnosed and untreated. Many mothers are hesitant to reveal their symptoms to family and clinicians, fearing they’ll be judged on their parenting. A 2017 study found that suicide accounted for roughly 5% of perinatal deaths among women in Canada, with most of those deaths occurring in the first 3 months in the year after giving birth.
“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness – even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research, said in a statement about the approval. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”
The other approved therapy for postpartum depression is the intravenous agent brexanolone (Zulresso; Sage). But the product requires prolonged infusions in hospital settings and costs $34,000.
FDA approval of Zurzuvae was based in part on data reported in a 2023 study in the American Journal of Psychiatry, which showed that the drug led to significantly greater improvement in depressive symptoms at 15 days compared with the placebo group. Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).
Patients with anxiety who received the active drug experienced improvement in related symptoms compared with the patients who received a placebo.
The most common adverse events reported in the trial were somnolence and headaches. Weight gain, sexual dysfunction, withdrawal symptoms, and increased suicidal ideation or behavior were not observed.
The packaging for Zurzuvae will include a boxed warning noting that the drug can affect a user’s ability to drive and perform other potentially hazardous activities, possibly without their knowledge of the impairment, the FDA said. As a result, people who use Zurzuvae should not drive or operate heavy machinery for at least 12 hours after taking the pill.
A version of this article first appeared on Medscape.com.
a condition that affects an estimated one in seven mothers in the United States.
The pill, zuranolone (Zurzuvae), is a neuroactive steroid that acts on GABAA receptors in the brain responsible for regulating mood, arousal, behavior, and cognition, according to Biogen, which, along with Sage Therapeutics, developed the product. The recommended dose for Zurzuvae is 50 mg taken once daily for 14 days, in the evening with a fatty meal, according to the FDA.
Postpartum depression often goes undiagnosed and untreated. Many mothers are hesitant to reveal their symptoms to family and clinicians, fearing they’ll be judged on their parenting. A 2017 study found that suicide accounted for roughly 5% of perinatal deaths among women in Canada, with most of those deaths occurring in the first 3 months in the year after giving birth.
“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness – even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research, said in a statement about the approval. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”
The other approved therapy for postpartum depression is the intravenous agent brexanolone (Zulresso; Sage). But the product requires prolonged infusions in hospital settings and costs $34,000.
FDA approval of Zurzuvae was based in part on data reported in a 2023 study in the American Journal of Psychiatry, which showed that the drug led to significantly greater improvement in depressive symptoms at 15 days compared with the placebo group. Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).
Patients with anxiety who received the active drug experienced improvement in related symptoms compared with the patients who received a placebo.
The most common adverse events reported in the trial were somnolence and headaches. Weight gain, sexual dysfunction, withdrawal symptoms, and increased suicidal ideation or behavior were not observed.
The packaging for Zurzuvae will include a boxed warning noting that the drug can affect a user’s ability to drive and perform other potentially hazardous activities, possibly without their knowledge of the impairment, the FDA said. As a result, people who use Zurzuvae should not drive or operate heavy machinery for at least 12 hours after taking the pill.
A version of this article first appeared on Medscape.com.
Rising viral load on dolutegravir? Investigators try fix before switch
Brisbane, Australia – , according to new data from the ADVANCE trial.
“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” said Andrew Hill, MD, from the department of pharmacology and therapeutics at the University of Liverpool, England.
The new data was presented here at the International AIDS Society conference on HIV Science. The ADVANCE trial is a three-arm randomized study involving 1,053 treatment-naive individuals comparing two triple-therapy combinations — dolutegravir, emtricitabine, and one of two tenofovir prodrugs – with a standard care regimen of tenofovir disoproxil fumarate, emtricitabine, and efavirenz.
Although the usual approach for someone in a clinical trial who experiences elevations in HIV RNA levels while on a dolutegravir-based treatment is to switch them to another therapy, the ADVANCE investigators opted for a different strategy.
“We actually continued treatment despite high viral load, and we didn’t have standard discontinuation preferences,” Dr. Hill said at the meeting. They instead provided counseling about adherence, which gave an opportunity to examine viral resuppression rates in participants in both the dolutegravir and efavirenz arms.
This revealed that 95% of patients in the two dolutegravir arms of the study were able to achieve resuppression of their viral load – defined as below 50 viral RNA copies per mL – without any emergence of resistance.
The guidelines
Current World Health Organization guidelines recommend that anyone whose viral load goes above 1,000 copies per mL who is on a non-nucleoside reverse transcriptase inhibitor such as efavirenz should be switched to an appropriate regimen.
Those who experience viremia on an integrase inhibitor such as dolutegravir should receive adherence counseling, have a repeat viral load test done in 3 months, and – if their viral load is still elevated – be switched to another regimen.
Dr. Hill and his team were examining how this might play out in a clinical trial setting and they found that there were a similar number of episodes of initial virologic failure in both the dolutegravir and efavirenz groups.
But after adherence counseling, testing for resistance and – if no resistance was evident – continuation with treatment, they saw differences emerge between the two groups.
“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” he said.
Time to viral resuppression
At 24 weeks after restarting treatment, 88% of people in the dolutegravir group had resuppressed their viral RNA, compared with 46% of people in the efavirenz group. At 48 weeks, those figures were 95% and 66%, respectively.
Dr. Hill pointed out that a significant number of people were lost to follow-up after virologic failure, and genotyping was not performed at baseline.
We addressed the question of how much adherence counseling should be undertaken in people who experienced viremia while on dolutegravir therapy, Dr. Hill said, particularly as there were often very good reasons for lack of adherence, such as homelessness.
“If you can get through those difficult phases, people can go back on their meds,” he said in an interview. “It’s almost a sociological problem rather than a clinical issue.”
And with efavirenz and the lower rates of resuppression observed in the study, Dr. Hill said it was a more fragile drug, so viremia therefore provided the opportunity for resistance to emerge, “and then once the resistant virus is there, you can’t get virus undetectable.”
Laura Waters, MD, a genitourinary and HIV medicine consultant at the Mortimer Market Centre in London, who was not involved in the study, said the results support recommendations to give people on drugs such as dolutegravir, which have a high genetic barrier to resistance, more time to improve their adherence before switching to another therapy.
“Although it provides that reassuring proof of concept, it doesn’t negate the importance of having to continue to monitor, because nothing is infallible,” she told this news organization. “We’ve talked about high-barrier drugs in the past, and you do start seeing resistance emerge.”
A version of this article first appeared on Medscape.com.
Brisbane, Australia – , according to new data from the ADVANCE trial.
“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” said Andrew Hill, MD, from the department of pharmacology and therapeutics at the University of Liverpool, England.
The new data was presented here at the International AIDS Society conference on HIV Science. The ADVANCE trial is a three-arm randomized study involving 1,053 treatment-naive individuals comparing two triple-therapy combinations — dolutegravir, emtricitabine, and one of two tenofovir prodrugs – with a standard care regimen of tenofovir disoproxil fumarate, emtricitabine, and efavirenz.
Although the usual approach for someone in a clinical trial who experiences elevations in HIV RNA levels while on a dolutegravir-based treatment is to switch them to another therapy, the ADVANCE investigators opted for a different strategy.
“We actually continued treatment despite high viral load, and we didn’t have standard discontinuation preferences,” Dr. Hill said at the meeting. They instead provided counseling about adherence, which gave an opportunity to examine viral resuppression rates in participants in both the dolutegravir and efavirenz arms.
This revealed that 95% of patients in the two dolutegravir arms of the study were able to achieve resuppression of their viral load – defined as below 50 viral RNA copies per mL – without any emergence of resistance.
The guidelines
Current World Health Organization guidelines recommend that anyone whose viral load goes above 1,000 copies per mL who is on a non-nucleoside reverse transcriptase inhibitor such as efavirenz should be switched to an appropriate regimen.
Those who experience viremia on an integrase inhibitor such as dolutegravir should receive adherence counseling, have a repeat viral load test done in 3 months, and – if their viral load is still elevated – be switched to another regimen.
Dr. Hill and his team were examining how this might play out in a clinical trial setting and they found that there were a similar number of episodes of initial virologic failure in both the dolutegravir and efavirenz groups.
But after adherence counseling, testing for resistance and – if no resistance was evident – continuation with treatment, they saw differences emerge between the two groups.
“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” he said.
Time to viral resuppression
At 24 weeks after restarting treatment, 88% of people in the dolutegravir group had resuppressed their viral RNA, compared with 46% of people in the efavirenz group. At 48 weeks, those figures were 95% and 66%, respectively.
Dr. Hill pointed out that a significant number of people were lost to follow-up after virologic failure, and genotyping was not performed at baseline.
We addressed the question of how much adherence counseling should be undertaken in people who experienced viremia while on dolutegravir therapy, Dr. Hill said, particularly as there were often very good reasons for lack of adherence, such as homelessness.
“If you can get through those difficult phases, people can go back on their meds,” he said in an interview. “It’s almost a sociological problem rather than a clinical issue.”
And with efavirenz and the lower rates of resuppression observed in the study, Dr. Hill said it was a more fragile drug, so viremia therefore provided the opportunity for resistance to emerge, “and then once the resistant virus is there, you can’t get virus undetectable.”
Laura Waters, MD, a genitourinary and HIV medicine consultant at the Mortimer Market Centre in London, who was not involved in the study, said the results support recommendations to give people on drugs such as dolutegravir, which have a high genetic barrier to resistance, more time to improve their adherence before switching to another therapy.
“Although it provides that reassuring proof of concept, it doesn’t negate the importance of having to continue to monitor, because nothing is infallible,” she told this news organization. “We’ve talked about high-barrier drugs in the past, and you do start seeing resistance emerge.”
A version of this article first appeared on Medscape.com.
Brisbane, Australia – , according to new data from the ADVANCE trial.
“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” said Andrew Hill, MD, from the department of pharmacology and therapeutics at the University of Liverpool, England.
The new data was presented here at the International AIDS Society conference on HIV Science. The ADVANCE trial is a three-arm randomized study involving 1,053 treatment-naive individuals comparing two triple-therapy combinations — dolutegravir, emtricitabine, and one of two tenofovir prodrugs – with a standard care regimen of tenofovir disoproxil fumarate, emtricitabine, and efavirenz.
Although the usual approach for someone in a clinical trial who experiences elevations in HIV RNA levels while on a dolutegravir-based treatment is to switch them to another therapy, the ADVANCE investigators opted for a different strategy.
“We actually continued treatment despite high viral load, and we didn’t have standard discontinuation preferences,” Dr. Hill said at the meeting. They instead provided counseling about adherence, which gave an opportunity to examine viral resuppression rates in participants in both the dolutegravir and efavirenz arms.
This revealed that 95% of patients in the two dolutegravir arms of the study were able to achieve resuppression of their viral load – defined as below 50 viral RNA copies per mL – without any emergence of resistance.
The guidelines
Current World Health Organization guidelines recommend that anyone whose viral load goes above 1,000 copies per mL who is on a non-nucleoside reverse transcriptase inhibitor such as efavirenz should be switched to an appropriate regimen.
Those who experience viremia on an integrase inhibitor such as dolutegravir should receive adherence counseling, have a repeat viral load test done in 3 months, and – if their viral load is still elevated – be switched to another regimen.
Dr. Hill and his team were examining how this might play out in a clinical trial setting and they found that there were a similar number of episodes of initial virologic failure in both the dolutegravir and efavirenz groups.
But after adherence counseling, testing for resistance and – if no resistance was evident – continuation with treatment, they saw differences emerge between the two groups.
“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” he said.
Time to viral resuppression
At 24 weeks after restarting treatment, 88% of people in the dolutegravir group had resuppressed their viral RNA, compared with 46% of people in the efavirenz group. At 48 weeks, those figures were 95% and 66%, respectively.
Dr. Hill pointed out that a significant number of people were lost to follow-up after virologic failure, and genotyping was not performed at baseline.
We addressed the question of how much adherence counseling should be undertaken in people who experienced viremia while on dolutegravir therapy, Dr. Hill said, particularly as there were often very good reasons for lack of adherence, such as homelessness.
“If you can get through those difficult phases, people can go back on their meds,” he said in an interview. “It’s almost a sociological problem rather than a clinical issue.”
And with efavirenz and the lower rates of resuppression observed in the study, Dr. Hill said it was a more fragile drug, so viremia therefore provided the opportunity for resistance to emerge, “and then once the resistant virus is there, you can’t get virus undetectable.”
Laura Waters, MD, a genitourinary and HIV medicine consultant at the Mortimer Market Centre in London, who was not involved in the study, said the results support recommendations to give people on drugs such as dolutegravir, which have a high genetic barrier to resistance, more time to improve their adherence before switching to another therapy.
“Although it provides that reassuring proof of concept, it doesn’t negate the importance of having to continue to monitor, because nothing is infallible,” she told this news organization. “We’ve talked about high-barrier drugs in the past, and you do start seeing resistance emerge.”
A version of this article first appeared on Medscape.com.
AT IAS 2023