Ob.Gyn. News

Lenacapavir, a twice-yearly injectable HIV-1 capsid inhibitor, has shown 100% efficacy in preventing HIV in women at a high risk for infection, according to an interim analysis of the phase 3 PURPOSE 1 trial.

The results were so promising that the independent data monitoring committee recommended that Gilead Sciences stop the blinded phase of the trial and offer open-label lenacapavir to all participants.

The results were both unexpected and exciting. “I’ve been in the HIV field for a really long time, and there’s no other phase 3 PrEP trial that found zero infections,” said Moupali Das, MD, PhD, executive director of clinical development at Gilead Sciences, Foster City, California.

PURPOSE 1 is evaluating the safety and efficacy of two regimens — twice-yearly subcutaneous lenacapavir for pre-exposure prophylaxis and once-daily oral Descovy (emtricitabine 200 mg and tenofovir alafenamide 25 mg) — in women and girls aged 16-25 years. The two drugs are being compared with the standard once-daily oral Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg).

There were no cases of HIV infection among the more than 2000 women in the lenacapavir group; in contrast, the incidence of HIV in the Descovy group was 2.02 per 100 person-years and in the Truvada group was 1.69 per 100 person-years.

The background incidence of HIV, one of the primary endpoints of the trial, was 2.41 per 100 person-years with lenacapavir. All the drugs were shown to be safe and well tolerated, and the full interim data from the trial will be released at an upcoming conference, according to Dr. Das.
 

No New Cases

The medical community is “thrilled” with the results so far, said Monica Gandhi, MD, director of the UCSF-Gladstone Center for AIDS Research. “We have to wait for the full data, but so far, it has been 100% effective and far superior to other treatments.”

Dr. Gandhi said she is waiting to see more details on side effects and tolerability, as well as discontinuation rates in the trial and the reasons people dropped out. For example, lenacapavir tends to cause nodules to form under the skin, which are the depots from which the drug is released over the course of 6 months. Gandhi said she is interested in whether any participants found them bothersome enough to discontinue the treatment.

The global HIV epidemic is still ongoing, with 1.3 million new infections in 2022, and existing oral PrEP options, and even the long-acting injectable cabotegravir, have so far failed to make as much of a dent in infection rates as hoped, said Dr. Gandhi. “We’ve been waiting for another option.”

The twice-yearly lenacapavir shot is easy and convenient to administer, compared with oral PrEP. Many people — especially younger individuals such as those enrolled in PURPOSE 1 — find it difficult to remember to take the pills every day.
 

A Discreet Option

Many participants in the trial said that they were uncomfortable with the stigma that can be attached to HIV PrEP. They did not want people to see the pill bottle in their house or hear it rattling in their purse. So an injection given just twice a year in a doctor’s office is attractive.

“This is a discrete option. People were very excited about the privacy and not having to take daily pills,” said Dr. Das. “PrEP only works if you take it.”

Better adherence to the treatment regimen is likely one reason that lenacapavir outperformed oral PrEP. But lenacapavir also has a unique mechanism of action as a multistage viral capsid inhibitor, Dr. Das said. It targets the capsid both before and after the virus integrates into the nucleus, which could be another reason for its potency.

Although the results are encouraging, there is still some concern about how accessible the drug will be, especially in low- and middle-income countries where the burden of HIV is the highest. “No one has any clue on how Gilead plans to make this accessible,” said Dr. Gandhi.
 

Access Issues

The company has not signed up for the Medicines Patent Pool (MPP) to allow companies to manufacture generic formulations of lenacapavir, which Dr. Gandhi said is the traditional route to provide cheaper alternatives in poorer countries. The “disastrous” rollout of injectable cabotegravir, which is still not widely available in lower-income countries, is a worrying precedent.

Gilead Sciences confirmed that all 5300 participants in the PURPOSE 1 study will have the option to continue receiving lenacapavir until the drug is generally available in their country. The company has committed to ensuring a dedicated Gilead Sciences supply in the countries where the need is the greatest until voluntary licensing partners are able to supply high-quality, low-cost versions of lenacapavir.

And rather than going through the third-party MPP, Gilead Sciences is negotiating a voluntary licensing program directly with other partners to supply generic versions of the drug in poorer countries.

Lenacapavir is already approved for the treatment of multidrug-resistant HIV but is not yet approved for HIV prevention. A sister trial, PURPOSE 2, is ongoing and is testing lenacapavir in men who have sex with men and in transgender men, transgender women, and nonbinary individuals who have sex with partners assigned male at birth. Should those results, expected by the end of 2024 or early 2025, be positive, the company will move forward with regulatory filings for lenacapavir PrEP.

Three other trials are also ongoing. PURPOSE 3 and PURPOSE 4 are smaller US-based studies of women and people who inject drugs, and PURPOSE 5 is enrolling people at a high risk for HIV in France and the United Kingdom to provide European data for European regulators.

A version of this article first appeared on Medscape.com.

Lenacapavir, a twice-yearly injectable HIV-1 capsid inhibitor, has shown 100% efficacy in preventing HIV in women at a high risk for infection, according to an interim analysis of the phase 3 PURPOSE 1 trial.

The results were so promising that the independent data monitoring committee recommended that Gilead Sciences stop the blinded phase of the trial and offer open-label lenacapavir to all participants.

The results were both unexpected and exciting. “I’ve been in the HIV field for a really long time, and there’s no other phase 3 PrEP trial that found zero infections,” said Moupali Das, MD, PhD, executive director of clinical development at Gilead Sciences, Foster City, California.

PURPOSE 1 is evaluating the safety and efficacy of two regimens — twice-yearly subcutaneous lenacapavir for pre-exposure prophylaxis and once-daily oral Descovy (emtricitabine 200 mg and tenofovir alafenamide 25 mg) — in women and girls aged 16-25 years. The two drugs are being compared with the standard once-daily oral Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg).

There were no cases of HIV infection among the more than 2000 women in the lenacapavir group; in contrast, the incidence of HIV in the Descovy group was 2.02 per 100 person-years and in the Truvada group was 1.69 per 100 person-years.

The background incidence of HIV, one of the primary endpoints of the trial, was 2.41 per 100 person-years with lenacapavir. All the drugs were shown to be safe and well tolerated, and the full interim data from the trial will be released at an upcoming conference, according to Dr. Das.
 

No New Cases

The medical community is “thrilled” with the results so far, said Monica Gandhi, MD, director of the UCSF-Gladstone Center for AIDS Research. “We have to wait for the full data, but so far, it has been 100% effective and far superior to other treatments.”

Dr. Gandhi said she is waiting to see more details on side effects and tolerability, as well as discontinuation rates in the trial and the reasons people dropped out. For example, lenacapavir tends to cause nodules to form under the skin, which are the depots from which the drug is released over the course of 6 months. Gandhi said she is interested in whether any participants found them bothersome enough to discontinue the treatment.

The global HIV epidemic is still ongoing, with 1.3 million new infections in 2022, and existing oral PrEP options, and even the long-acting injectable cabotegravir, have so far failed to make as much of a dent in infection rates as hoped, said Dr. Gandhi. “We’ve been waiting for another option.”

The twice-yearly lenacapavir shot is easy and convenient to administer, compared with oral PrEP. Many people — especially younger individuals such as those enrolled in PURPOSE 1 — find it difficult to remember to take the pills every day.
 

A Discreet Option

Many participants in the trial said that they were uncomfortable with the stigma that can be attached to HIV PrEP. They did not want people to see the pill bottle in their house or hear it rattling in their purse. So an injection given just twice a year in a doctor’s office is attractive.

“This is a discrete option. People were very excited about the privacy and not having to take daily pills,” said Dr. Das. “PrEP only works if you take it.”

Better adherence to the treatment regimen is likely one reason that lenacapavir outperformed oral PrEP. But lenacapavir also has a unique mechanism of action as a multistage viral capsid inhibitor, Dr. Das said. It targets the capsid both before and after the virus integrates into the nucleus, which could be another reason for its potency.

Although the results are encouraging, there is still some concern about how accessible the drug will be, especially in low- and middle-income countries where the burden of HIV is the highest. “No one has any clue on how Gilead plans to make this accessible,” said Dr. Gandhi.
 

Access Issues

The company has not signed up for the Medicines Patent Pool (MPP) to allow companies to manufacture generic formulations of lenacapavir, which Dr. Gandhi said is the traditional route to provide cheaper alternatives in poorer countries. The “disastrous” rollout of injectable cabotegravir, which is still not widely available in lower-income countries, is a worrying precedent.

Gilead Sciences confirmed that all 5300 participants in the PURPOSE 1 study will have the option to continue receiving lenacapavir until the drug is generally available in their country. The company has committed to ensuring a dedicated Gilead Sciences supply in the countries where the need is the greatest until voluntary licensing partners are able to supply high-quality, low-cost versions of lenacapavir.

And rather than going through the third-party MPP, Gilead Sciences is negotiating a voluntary licensing program directly with other partners to supply generic versions of the drug in poorer countries.

Lenacapavir is already approved for the treatment of multidrug-resistant HIV but is not yet approved for HIV prevention. A sister trial, PURPOSE 2, is ongoing and is testing lenacapavir in men who have sex with men and in transgender men, transgender women, and nonbinary individuals who have sex with partners assigned male at birth. Should those results, expected by the end of 2024 or early 2025, be positive, the company will move forward with regulatory filings for lenacapavir PrEP.

Three other trials are also ongoing. PURPOSE 3 and PURPOSE 4 are smaller US-based studies of women and people who inject drugs, and PURPOSE 5 is enrolling people at a high risk for HIV in France and the United Kingdom to provide European data for European regulators.

A version of this article first appeared on Medscape.com.

Lenacapavir, a twice-yearly injectable HIV-1 capsid inhibitor, has shown 100% efficacy in preventing HIV in women at a high risk for infection, according to an interim analysis of the phase 3 PURPOSE 1 trial.

The results were so promising that the independent data monitoring committee recommended that Gilead Sciences stop the blinded phase of the trial and offer open-label lenacapavir to all participants.

The results were both unexpected and exciting. “I’ve been in the HIV field for a really long time, and there’s no other phase 3 PrEP trial that found zero infections,” said Moupali Das, MD, PhD, executive director of clinical development at Gilead Sciences, Foster City, California.

PURPOSE 1 is evaluating the safety and efficacy of two regimens — twice-yearly subcutaneous lenacapavir for pre-exposure prophylaxis and once-daily oral Descovy (emtricitabine 200 mg and tenofovir alafenamide 25 mg) — in women and girls aged 16-25 years. The two drugs are being compared with the standard once-daily oral Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg).

There were no cases of HIV infection among the more than 2000 women in the lenacapavir group; in contrast, the incidence of HIV in the Descovy group was 2.02 per 100 person-years and in the Truvada group was 1.69 per 100 person-years.

The background incidence of HIV, one of the primary endpoints of the trial, was 2.41 per 100 person-years with lenacapavir. All the drugs were shown to be safe and well tolerated, and the full interim data from the trial will be released at an upcoming conference, according to Dr. Das.
 

No New Cases

The medical community is “thrilled” with the results so far, said Monica Gandhi, MD, director of the UCSF-Gladstone Center for AIDS Research. “We have to wait for the full data, but so far, it has been 100% effective and far superior to other treatments.”

Dr. Gandhi said she is waiting to see more details on side effects and tolerability, as well as discontinuation rates in the trial and the reasons people dropped out. For example, lenacapavir tends to cause nodules to form under the skin, which are the depots from which the drug is released over the course of 6 months. Gandhi said she is interested in whether any participants found them bothersome enough to discontinue the treatment.

The global HIV epidemic is still ongoing, with 1.3 million new infections in 2022, and existing oral PrEP options, and even the long-acting injectable cabotegravir, have so far failed to make as much of a dent in infection rates as hoped, said Dr. Gandhi. “We’ve been waiting for another option.”

The twice-yearly lenacapavir shot is easy and convenient to administer, compared with oral PrEP. Many people — especially younger individuals such as those enrolled in PURPOSE 1 — find it difficult to remember to take the pills every day.
 

A Discreet Option

Many participants in the trial said that they were uncomfortable with the stigma that can be attached to HIV PrEP. They did not want people to see the pill bottle in their house or hear it rattling in their purse. So an injection given just twice a year in a doctor’s office is attractive.

“This is a discrete option. People were very excited about the privacy and not having to take daily pills,” said Dr. Das. “PrEP only works if you take it.”

Better adherence to the treatment regimen is likely one reason that lenacapavir outperformed oral PrEP. But lenacapavir also has a unique mechanism of action as a multistage viral capsid inhibitor, Dr. Das said. It targets the capsid both before and after the virus integrates into the nucleus, which could be another reason for its potency.

Although the results are encouraging, there is still some concern about how accessible the drug will be, especially in low- and middle-income countries where the burden of HIV is the highest. “No one has any clue on how Gilead plans to make this accessible,” said Dr. Gandhi.
 

Access Issues

The company has not signed up for the Medicines Patent Pool (MPP) to allow companies to manufacture generic formulations of lenacapavir, which Dr. Gandhi said is the traditional route to provide cheaper alternatives in poorer countries. The “disastrous” rollout of injectable cabotegravir, which is still not widely available in lower-income countries, is a worrying precedent.

Gilead Sciences confirmed that all 5300 participants in the PURPOSE 1 study will have the option to continue receiving lenacapavir until the drug is generally available in their country. The company has committed to ensuring a dedicated Gilead Sciences supply in the countries where the need is the greatest until voluntary licensing partners are able to supply high-quality, low-cost versions of lenacapavir.

And rather than going through the third-party MPP, Gilead Sciences is negotiating a voluntary licensing program directly with other partners to supply generic versions of the drug in poorer countries.

Lenacapavir is already approved for the treatment of multidrug-resistant HIV but is not yet approved for HIV prevention. A sister trial, PURPOSE 2, is ongoing and is testing lenacapavir in men who have sex with men and in transgender men, transgender women, and nonbinary individuals who have sex with partners assigned male at birth. Should those results, expected by the end of 2024 or early 2025, be positive, the company will move forward with regulatory filings for lenacapavir PrEP.

Three other trials are also ongoing. PURPOSE 3 and PURPOSE 4 are smaller US-based studies of women and people who inject drugs, and PURPOSE 5 is enrolling people at a high risk for HIV in France and the United Kingdom to provide European data for European regulators.

A version of this article first appeared on Medscape.com.

CHICAGO — The landscape of antibody-drug conjugates, or ADCs, continues to grow more crowded in metastatic breast cancer. Indications are expanding, new agents are emerging, combinations with other drug classes are being tested, and many patients with this disease are now receiving more than one ADC.

ADCs use antibodies to bind to the surface proteins of cancer cells to deliver a potent payload of cytotoxic chemotherapy. Three are approved for use in pretreated patients with metastatic breast cancer: sacituzumab govitecan, or SG, for patients with triple-negative disease; trastuzumab deruxtecan, or T-DXd, for patients with HER2-positive and HER2-low disease; and trastuzumab emtansine, or T-DM1, for patients with HER2-positive disease. A fourth agent, datopotamab deruxtecan, or Dato-DXd, is being assessed by the US Food and Drug Administration (FDA) for use in pretreated HR-positive, HER2-negative patients, and others, including sacituzumab tirumotecan, are being tested in clinical trials.At the annual meeting of the American Society of Clinical Oncology, T-DXd (Enhertu, AstraZeneca) showed better progression free survival than chemotherapy in people with HR-positive, HER 2-low metastatic breast cancers. These findings, from the DESTINY Breast-06 trial, were among the most talked-about at ASCO, and are likely to change clinical practice (J Clin Oncol. 2024;42[suppl 17; abstr LBA1000]).

But other ADC results presented at ASCO showed that there is still much to be worked out about the timing and sequencing of these agents, as well as their synergy with other drug classes, in metastatic breast cancer.
 

An ADC gets its first test, and falls short

Antonio Giordano, MD, PhD, of the Dana-Farber Cancer Institute in Boston, presented findings from an open-label phase 2 study of the ADC enfortumab vedotin (EV), an agent currently approved for use in advanced or metastatic urothelial cancer, at ASCO. This study included two cohorts of previously treated metastatic breast cancer patients: one with triple-negative disease (n = 42) and the other with HR-positive HER2-negative (n = 45).

Dr. Giordano and his colleagues’ study is the first to look at this ADC in breast cancer. EV’s antibody targets the cell adhesion molecule Nectin-4.

The researchers found that though EV demonstrated anti-tumor activity in both cohorts — with 19% of the triple-negative patients and 15.6% of the HR-positive/HER2-negative patients responding — the results did not meet the prespecified response thresholds for either cohort. (J Clin Oncol. 2024;42[suppl 16; abstr 1005]).

In an interview, Dr. Giordano said that studies in urothelial cancer had shown better response to EV associated with more expression of Nectin-4, but this study did not see such clear associations between expression and response. While there is no question that Nectin-4 is highly expressed in breast cancer and therefore a viable target, he said, “it may need to be looked at a little more deeply.”

It could also be the case, Dr. Giordano said, that the effect of EV’s payload may have been less robust in participants who had been previously treated with taxane chemotherapy, as nearly all patients in the two cohorts were.

“Taxanes are microtubule disruptors. And with this drug we had a payload with pretty much the same mechanism of action,” Dr. Giordano said. Ideally, he said, he would like to test the agent in a first-line setting, possibly in combination with an immunotherapy agent.

The timing of ADCs is as important as their targets and their payloads — and something that investigators are still struggling to figure out, he said.

A third of the patients in the triple-negative cohort of his study had been previously treated with SG, and a handful of individuals with T-Dxd, he noted.

“We’re in the middle of an ADC revolution,” he said. “It’s really key to figure out the best sequencing for a patient and if it’s actually worth it to do it. Very often we see patients respond best to the first ADC. But sometimes we see patients that do not respond to the first ADC and then they respond to the second one. It’s not very frequent, but it happens.”
 

Hint of Benefit from Adding Immunotherapy to SG

In a separate presentation at ASCO, Ana C. Garrido-Castro, MD, also of the Dana-Farber Cancer Institute, presented results from the SACI-IO HR+ trial, a randomized phase 2 study of SG (Trodelvy, Gilead) with and without pembrolizumab (Keytruda, Merck) in 104 patients with metastatic HR-positive/HER2-negative breast cancer who received prior endocrine therapy and up to one chemotherapy regimen for advanced disease. SACI-IO HR+ is the first randomized trial to report the efficacy of a topoisomerase I-inhibitor ADC with an immune checkpoint inhibitor for the treatment of breast cancer.

The addition of the immune checkpoint inhibitor did not result in a significant improvement in median progression-free survival in the overall population, Dr. Garrido-Castro reported. Median PFS was 8.1 vs 6.2 months with the combination of SG plus pembrolizumab or sacituzumab govitecan alone, respectively. At a median follow-up of 12.5 months, there was also no significant difference seen in median overall survival (OS): 18.5 vs 18.0 months.

About 40% of participants were found to have PD-L1-positive tumors and, among this subgroup, there was a 4.4-month increase in median PFS and 6.0-month increase in median OS with the addition of pembrolizumab to SG, although this did not reach statistical significance. (J Clin Oncol. 2024;42[suppl 17; abstr LBA1004]).

“While the study did not demonstrate a statistically significant benefit with the addition of the immune checkpoint inhibitor to the ADC, there is an interesting signal for potential synergistic activity between the two agents, particularly in those patients with PD-L1 positive tumors,” Dr. Garrido-Castro said in an interview. She noted that the sample sizes for the PD-L1 subgroup were relatively small, and overall survival data are not yet mature.

A separate phase 3 study is looking at the experimental ADC called sacituzumab tirumotecan with and without pembrolizumab compared with chemotherapy in patients with metastatic HR-positive, HER2-negative breast cancer who have received prior endocrine therapy and no prior chemotherapy for metastatic disease, she said.

Similar to SG, sacituzumab tirumotecan is a TROP2-directed ADC with a topoisomerase I-inhibitor payload. With an estimated enrollment of 1,200 patients, this trial may help shed light on whether adding the immune checkpoint inhibitor to the topoisomerase I-inhibitor TROP2-directed ADC improves outcomes in the subgroup of patients with PD-L1 positive tumors, Dr. Garrido-Castro said.
 

Unlocking the Order and Timing of ADCs

Dr. Garrido-Castro is also leading a study that will evaluate the sequential use of ADCs in metastatic breast cancer. That trial, to be called TRADE-DXd, will enroll patients with HER2-low metastatic breast cancer who have received up to one prior line of chemotherapy and no previous topoisomerase I-inhibitors. Participants will receive either T-DXd or Dato-DXd as the first ADC, and then switch to the other ADC (Dato-DXd or T-DXd, respectively) at the time of progression, thus switching the target of the ADC from HER2 to TROP2 or vice versa.

“In real-world practice now, there are patients who receive sequential ADCs, because they are candidates for both,” Dr. Garrido-Castro explained. However, more robust data are needed to refine the selection of the initial antibody drug conjugate and to determine who is more likely to benefit from a second — or maybe even third — ADC.

“One potential mechanism of resistance to antibody drug conjugates is the downregulation of the target of the antibody drug conjugate,” Dr. Garrido-Castro said. “Thus, an important question is, if you modify the target of the ADC, is it possible to overcome that mechanism of resistance?” Another possible mechanism of resistance is to the chemotherapy payload of the ADCs, she said.

Dr. Garrido-Castro’s study will collect tumor samples and blood samples for the purposes of planned correlative analyses to try to better understand the mechanisms that drive response and resistance to these agents.

Dr. Giordano commented that Dr. Garrido-Castro’s study was likely to result in a much better understanding of ADCs and how to use them strategically.

At Dana-Farber, “we collect a lot of samples of patients receiving ADCs. And we are trying to do all kinds of work on circulating tumor DNA, immunohistochemistry expression, and protein expression,” he said. “We are trying to figure out how ADCs really work, and why they stop working.”

Dr. Giordano and colleagues’ study was funded by Astellas Pharma and by Seagen, which was bought by Pfizer in 2023. Dr. Giordano disclosed receiving consulting fees from Pfizer, and several of his coauthors reported relationships with this and other companies. Two were Astellas employees.

Dr. Garrido-Castro and colleagues’ study was funded by Merck and Gilead Sciences. Dr. Garrido-Castro disclosed receiving research support from Gilead Sciences, AstraZeneca, Daiichi Sankyo, Merck, Zenith Epigenetics, Bristol-Myers Squibb, Novartis, Biovica, Foundation Medicine, 4D Path, Precede Biosciences; scientific advisory board/consulting fees from AstraZeneca, Novartis, Daiichi Sankyo; speaker honoraria from AstraZeneca, Daiichi Sankyo; and other support from Roche/Genentech, Gilead Sciences, AstraZeneca, Daiichi Sankyo, Novartis, and Merck, while her coauthors reported similar relationships.

CHICAGO — The landscape of antibody-drug conjugates, or ADCs, continues to grow more crowded in metastatic breast cancer. Indications are expanding, new agents are emerging, combinations with other drug classes are being tested, and many patients with this disease are now receiving more than one ADC.

ADCs use antibodies to bind to the surface proteins of cancer cells to deliver a potent payload of cytotoxic chemotherapy. Three are approved for use in pretreated patients with metastatic breast cancer: sacituzumab govitecan, or SG, for patients with triple-negative disease; trastuzumab deruxtecan, or T-DXd, for patients with HER2-positive and HER2-low disease; and trastuzumab emtansine, or T-DM1, for patients with HER2-positive disease. A fourth agent, datopotamab deruxtecan, or Dato-DXd, is being assessed by the US Food and Drug Administration (FDA) for use in pretreated HR-positive, HER2-negative patients, and others, including sacituzumab tirumotecan, are being tested in clinical trials.At the annual meeting of the American Society of Clinical Oncology, T-DXd (Enhertu, AstraZeneca) showed better progression free survival than chemotherapy in people with HR-positive, HER 2-low metastatic breast cancers. These findings, from the DESTINY Breast-06 trial, were among the most talked-about at ASCO, and are likely to change clinical practice (J Clin Oncol. 2024;42[suppl 17; abstr LBA1000]).

But other ADC results presented at ASCO showed that there is still much to be worked out about the timing and sequencing of these agents, as well as their synergy with other drug classes, in metastatic breast cancer.
 

An ADC gets its first test, and falls short

Antonio Giordano, MD, PhD, of the Dana-Farber Cancer Institute in Boston, presented findings from an open-label phase 2 study of the ADC enfortumab vedotin (EV), an agent currently approved for use in advanced or metastatic urothelial cancer, at ASCO. This study included two cohorts of previously treated metastatic breast cancer patients: one with triple-negative disease (n = 42) and the other with HR-positive HER2-negative (n = 45).

Dr. Giordano and his colleagues’ study is the first to look at this ADC in breast cancer. EV’s antibody targets the cell adhesion molecule Nectin-4.

The researchers found that though EV demonstrated anti-tumor activity in both cohorts — with 19% of the triple-negative patients and 15.6% of the HR-positive/HER2-negative patients responding — the results did not meet the prespecified response thresholds for either cohort. (J Clin Oncol. 2024;42[suppl 16; abstr 1005]).

In an interview, Dr. Giordano said that studies in urothelial cancer had shown better response to EV associated with more expression of Nectin-4, but this study did not see such clear associations between expression and response. While there is no question that Nectin-4 is highly expressed in breast cancer and therefore a viable target, he said, “it may need to be looked at a little more deeply.”

It could also be the case, Dr. Giordano said, that the effect of EV’s payload may have been less robust in participants who had been previously treated with taxane chemotherapy, as nearly all patients in the two cohorts were.

“Taxanes are microtubule disruptors. And with this drug we had a payload with pretty much the same mechanism of action,” Dr. Giordano said. Ideally, he said, he would like to test the agent in a first-line setting, possibly in combination with an immunotherapy agent.

The timing of ADCs is as important as their targets and their payloads — and something that investigators are still struggling to figure out, he said.

A third of the patients in the triple-negative cohort of his study had been previously treated with SG, and a handful of individuals with T-Dxd, he noted.

“We’re in the middle of an ADC revolution,” he said. “It’s really key to figure out the best sequencing for a patient and if it’s actually worth it to do it. Very often we see patients respond best to the first ADC. But sometimes we see patients that do not respond to the first ADC and then they respond to the second one. It’s not very frequent, but it happens.”
 

Hint of Benefit from Adding Immunotherapy to SG

In a separate presentation at ASCO, Ana C. Garrido-Castro, MD, also of the Dana-Farber Cancer Institute, presented results from the SACI-IO HR+ trial, a randomized phase 2 study of SG (Trodelvy, Gilead) with and without pembrolizumab (Keytruda, Merck) in 104 patients with metastatic HR-positive/HER2-negative breast cancer who received prior endocrine therapy and up to one chemotherapy regimen for advanced disease. SACI-IO HR+ is the first randomized trial to report the efficacy of a topoisomerase I-inhibitor ADC with an immune checkpoint inhibitor for the treatment of breast cancer.

The addition of the immune checkpoint inhibitor did not result in a significant improvement in median progression-free survival in the overall population, Dr. Garrido-Castro reported. Median PFS was 8.1 vs 6.2 months with the combination of SG plus pembrolizumab or sacituzumab govitecan alone, respectively. At a median follow-up of 12.5 months, there was also no significant difference seen in median overall survival (OS): 18.5 vs 18.0 months.

About 40% of participants were found to have PD-L1-positive tumors and, among this subgroup, there was a 4.4-month increase in median PFS and 6.0-month increase in median OS with the addition of pembrolizumab to SG, although this did not reach statistical significance. (J Clin Oncol. 2024;42[suppl 17; abstr LBA1004]).

“While the study did not demonstrate a statistically significant benefit with the addition of the immune checkpoint inhibitor to the ADC, there is an interesting signal for potential synergistic activity between the two agents, particularly in those patients with PD-L1 positive tumors,” Dr. Garrido-Castro said in an interview. She noted that the sample sizes for the PD-L1 subgroup were relatively small, and overall survival data are not yet mature.

A separate phase 3 study is looking at the experimental ADC called sacituzumab tirumotecan with and without pembrolizumab compared with chemotherapy in patients with metastatic HR-positive, HER2-negative breast cancer who have received prior endocrine therapy and no prior chemotherapy for metastatic disease, she said.

Similar to SG, sacituzumab tirumotecan is a TROP2-directed ADC with a topoisomerase I-inhibitor payload. With an estimated enrollment of 1,200 patients, this trial may help shed light on whether adding the immune checkpoint inhibitor to the topoisomerase I-inhibitor TROP2-directed ADC improves outcomes in the subgroup of patients with PD-L1 positive tumors, Dr. Garrido-Castro said.
 

Unlocking the Order and Timing of ADCs

Dr. Garrido-Castro is also leading a study that will evaluate the sequential use of ADCs in metastatic breast cancer. That trial, to be called TRADE-DXd, will enroll patients with HER2-low metastatic breast cancer who have received up to one prior line of chemotherapy and no previous topoisomerase I-inhibitors. Participants will receive either T-DXd or Dato-DXd as the first ADC, and then switch to the other ADC (Dato-DXd or T-DXd, respectively) at the time of progression, thus switching the target of the ADC from HER2 to TROP2 or vice versa.

“In real-world practice now, there are patients who receive sequential ADCs, because they are candidates for both,” Dr. Garrido-Castro explained. However, more robust data are needed to refine the selection of the initial antibody drug conjugate and to determine who is more likely to benefit from a second — or maybe even third — ADC.

“One potential mechanism of resistance to antibody drug conjugates is the downregulation of the target of the antibody drug conjugate,” Dr. Garrido-Castro said. “Thus, an important question is, if you modify the target of the ADC, is it possible to overcome that mechanism of resistance?” Another possible mechanism of resistance is to the chemotherapy payload of the ADCs, she said.

Dr. Garrido-Castro’s study will collect tumor samples and blood samples for the purposes of planned correlative analyses to try to better understand the mechanisms that drive response and resistance to these agents.

Dr. Giordano commented that Dr. Garrido-Castro’s study was likely to result in a much better understanding of ADCs and how to use them strategically.

At Dana-Farber, “we collect a lot of samples of patients receiving ADCs. And we are trying to do all kinds of work on circulating tumor DNA, immunohistochemistry expression, and protein expression,” he said. “We are trying to figure out how ADCs really work, and why they stop working.”

Dr. Giordano and colleagues’ study was funded by Astellas Pharma and by Seagen, which was bought by Pfizer in 2023. Dr. Giordano disclosed receiving consulting fees from Pfizer, and several of his coauthors reported relationships with this and other companies. Two were Astellas employees.

Dr. Garrido-Castro and colleagues’ study was funded by Merck and Gilead Sciences. Dr. Garrido-Castro disclosed receiving research support from Gilead Sciences, AstraZeneca, Daiichi Sankyo, Merck, Zenith Epigenetics, Bristol-Myers Squibb, Novartis, Biovica, Foundation Medicine, 4D Path, Precede Biosciences; scientific advisory board/consulting fees from AstraZeneca, Novartis, Daiichi Sankyo; speaker honoraria from AstraZeneca, Daiichi Sankyo; and other support from Roche/Genentech, Gilead Sciences, AstraZeneca, Daiichi Sankyo, Novartis, and Merck, while her coauthors reported similar relationships.

CHICAGO — The landscape of antibody-drug conjugates, or ADCs, continues to grow more crowded in metastatic breast cancer. Indications are expanding, new agents are emerging, combinations with other drug classes are being tested, and many patients with this disease are now receiving more than one ADC.

ADCs use antibodies to bind to the surface proteins of cancer cells to deliver a potent payload of cytotoxic chemotherapy. Three are approved for use in pretreated patients with metastatic breast cancer: sacituzumab govitecan, or SG, for patients with triple-negative disease; trastuzumab deruxtecan, or T-DXd, for patients with HER2-positive and HER2-low disease; and trastuzumab emtansine, or T-DM1, for patients with HER2-positive disease. A fourth agent, datopotamab deruxtecan, or Dato-DXd, is being assessed by the US Food and Drug Administration (FDA) for use in pretreated HR-positive, HER2-negative patients, and others, including sacituzumab tirumotecan, are being tested in clinical trials.At the annual meeting of the American Society of Clinical Oncology, T-DXd (Enhertu, AstraZeneca) showed better progression free survival than chemotherapy in people with HR-positive, HER 2-low metastatic breast cancers. These findings, from the DESTINY Breast-06 trial, were among the most talked-about at ASCO, and are likely to change clinical practice (J Clin Oncol. 2024;42[suppl 17; abstr LBA1000]).

But other ADC results presented at ASCO showed that there is still much to be worked out about the timing and sequencing of these agents, as well as their synergy with other drug classes, in metastatic breast cancer.
 

An ADC gets its first test, and falls short

Antonio Giordano, MD, PhD, of the Dana-Farber Cancer Institute in Boston, presented findings from an open-label phase 2 study of the ADC enfortumab vedotin (EV), an agent currently approved for use in advanced or metastatic urothelial cancer, at ASCO. This study included two cohorts of previously treated metastatic breast cancer patients: one with triple-negative disease (n = 42) and the other with HR-positive HER2-negative (n = 45).

Dr. Giordano and his colleagues’ study is the first to look at this ADC in breast cancer. EV’s antibody targets the cell adhesion molecule Nectin-4.

The researchers found that though EV demonstrated anti-tumor activity in both cohorts — with 19% of the triple-negative patients and 15.6% of the HR-positive/HER2-negative patients responding — the results did not meet the prespecified response thresholds for either cohort. (J Clin Oncol. 2024;42[suppl 16; abstr 1005]).

In an interview, Dr. Giordano said that studies in urothelial cancer had shown better response to EV associated with more expression of Nectin-4, but this study did not see such clear associations between expression and response. While there is no question that Nectin-4 is highly expressed in breast cancer and therefore a viable target, he said, “it may need to be looked at a little more deeply.”

It could also be the case, Dr. Giordano said, that the effect of EV’s payload may have been less robust in participants who had been previously treated with taxane chemotherapy, as nearly all patients in the two cohorts were.

“Taxanes are microtubule disruptors. And with this drug we had a payload with pretty much the same mechanism of action,” Dr. Giordano said. Ideally, he said, he would like to test the agent in a first-line setting, possibly in combination with an immunotherapy agent.

The timing of ADCs is as important as their targets and their payloads — and something that investigators are still struggling to figure out, he said.

A third of the patients in the triple-negative cohort of his study had been previously treated with SG, and a handful of individuals with T-Dxd, he noted.

“We’re in the middle of an ADC revolution,” he said. “It’s really key to figure out the best sequencing for a patient and if it’s actually worth it to do it. Very often we see patients respond best to the first ADC. But sometimes we see patients that do not respond to the first ADC and then they respond to the second one. It’s not very frequent, but it happens.”
 

Hint of Benefit from Adding Immunotherapy to SG

In a separate presentation at ASCO, Ana C. Garrido-Castro, MD, also of the Dana-Farber Cancer Institute, presented results from the SACI-IO HR+ trial, a randomized phase 2 study of SG (Trodelvy, Gilead) with and without pembrolizumab (Keytruda, Merck) in 104 patients with metastatic HR-positive/HER2-negative breast cancer who received prior endocrine therapy and up to one chemotherapy regimen for advanced disease. SACI-IO HR+ is the first randomized trial to report the efficacy of a topoisomerase I-inhibitor ADC with an immune checkpoint inhibitor for the treatment of breast cancer.

The addition of the immune checkpoint inhibitor did not result in a significant improvement in median progression-free survival in the overall population, Dr. Garrido-Castro reported. Median PFS was 8.1 vs 6.2 months with the combination of SG plus pembrolizumab or sacituzumab govitecan alone, respectively. At a median follow-up of 12.5 months, there was also no significant difference seen in median overall survival (OS): 18.5 vs 18.0 months.

About 40% of participants were found to have PD-L1-positive tumors and, among this subgroup, there was a 4.4-month increase in median PFS and 6.0-month increase in median OS with the addition of pembrolizumab to SG, although this did not reach statistical significance. (J Clin Oncol. 2024;42[suppl 17; abstr LBA1004]).

“While the study did not demonstrate a statistically significant benefit with the addition of the immune checkpoint inhibitor to the ADC, there is an interesting signal for potential synergistic activity between the two agents, particularly in those patients with PD-L1 positive tumors,” Dr. Garrido-Castro said in an interview. She noted that the sample sizes for the PD-L1 subgroup were relatively small, and overall survival data are not yet mature.

A separate phase 3 study is looking at the experimental ADC called sacituzumab tirumotecan with and without pembrolizumab compared with chemotherapy in patients with metastatic HR-positive, HER2-negative breast cancer who have received prior endocrine therapy and no prior chemotherapy for metastatic disease, she said.

Similar to SG, sacituzumab tirumotecan is a TROP2-directed ADC with a topoisomerase I-inhibitor payload. With an estimated enrollment of 1,200 patients, this trial may help shed light on whether adding the immune checkpoint inhibitor to the topoisomerase I-inhibitor TROP2-directed ADC improves outcomes in the subgroup of patients with PD-L1 positive tumors, Dr. Garrido-Castro said.
 

Unlocking the Order and Timing of ADCs

Dr. Garrido-Castro is also leading a study that will evaluate the sequential use of ADCs in metastatic breast cancer. That trial, to be called TRADE-DXd, will enroll patients with HER2-low metastatic breast cancer who have received up to one prior line of chemotherapy and no previous topoisomerase I-inhibitors. Participants will receive either T-DXd or Dato-DXd as the first ADC, and then switch to the other ADC (Dato-DXd or T-DXd, respectively) at the time of progression, thus switching the target of the ADC from HER2 to TROP2 or vice versa.

“In real-world practice now, there are patients who receive sequential ADCs, because they are candidates for both,” Dr. Garrido-Castro explained. However, more robust data are needed to refine the selection of the initial antibody drug conjugate and to determine who is more likely to benefit from a second — or maybe even third — ADC.

“One potential mechanism of resistance to antibody drug conjugates is the downregulation of the target of the antibody drug conjugate,” Dr. Garrido-Castro said. “Thus, an important question is, if you modify the target of the ADC, is it possible to overcome that mechanism of resistance?” Another possible mechanism of resistance is to the chemotherapy payload of the ADCs, she said.

Dr. Garrido-Castro’s study will collect tumor samples and blood samples for the purposes of planned correlative analyses to try to better understand the mechanisms that drive response and resistance to these agents.

Dr. Giordano commented that Dr. Garrido-Castro’s study was likely to result in a much better understanding of ADCs and how to use them strategically.

At Dana-Farber, “we collect a lot of samples of patients receiving ADCs. And we are trying to do all kinds of work on circulating tumor DNA, immunohistochemistry expression, and protein expression,” he said. “We are trying to figure out how ADCs really work, and why they stop working.”

Dr. Giordano and colleagues’ study was funded by Astellas Pharma and by Seagen, which was bought by Pfizer in 2023. Dr. Giordano disclosed receiving consulting fees from Pfizer, and several of his coauthors reported relationships with this and other companies. Two were Astellas employees.

Dr. Garrido-Castro and colleagues’ study was funded by Merck and Gilead Sciences. Dr. Garrido-Castro disclosed receiving research support from Gilead Sciences, AstraZeneca, Daiichi Sankyo, Merck, Zenith Epigenetics, Bristol-Myers Squibb, Novartis, Biovica, Foundation Medicine, 4D Path, Precede Biosciences; scientific advisory board/consulting fees from AstraZeneca, Novartis, Daiichi Sankyo; speaker honoraria from AstraZeneca, Daiichi Sankyo; and other support from Roche/Genentech, Gilead Sciences, AstraZeneca, Daiichi Sankyo, Novartis, and Merck, while her coauthors reported similar relationships.

As Pride Month drew to a close, the Supreme Court made a shocking announcement. For the first time in the history of the court, it is willing to hear a legal challenge regarding gender-affirming care for minors. The justices will review whether a 2023 Tennessee law, SB1, which bans hormone therapy, puberty blockers, and surgery for transgender minors, is unconstitutional. This is the first time the Supreme Court will directly weigh in on gender-affirming care.

There are few topics as politically and medically divisive as gender-affirming care for minors. When the World Professional Association for Transgender Health (WPATH) released its updated Standards of Care, SOC8, one of the noticeable changes to the document was its approach to caring for transgender children and adolescents.

Dr. Brandt

Before I highlight these recommendations and the ensuing controversy, it is imperative to establish proper terminology. Unfortunately, medical and legal terms often differ. Both activists and opponents use these terms interchangeably, which makes discourse about an already emotionally charged topic extremely difficult. From a legal perspective, the terms “minor” and “child” often refer to individuals under the age of majority. In the United States, the age of majority is 18. However, the term child also has a well-established medical definition. A child is an individual between the stages of infancy and puberty. Adolescence is a transitional period marked by the onset of puberty until adulthood (typically the age of majority). As medical providers, understanding these definitions is essential to identifying misinformation pertaining to this type of healthcare.

For the purposes of this article, I will be adhering to the medical terminology. Now, I want to be very clear. WPATH does not endorse surgical procedures on children. Furthermore, surgeons are not performing gender-affirming surgeries on children. On adolescents, rarely. But children, never.

According to the updated SOC8, the only acceptable gender-affirming intervention for children is psychosocial support.¹ This does not include puberty blockers, hormones, or surgery, but rather allowing a child to explore their gender identity by experimenting with different clothing, toys, hairstyles, and even an alternative name that aligns more closely with their gender identity.¹

It is only after children reach adolescence that medical, and in rare cases, surgical interventions, can be considered. Puberty blockers are appropriate for patients who have started puberty and experience gender dysphoria. These medications are reversible, and their purpose is to temporarily pause puberty to allow the adolescent to further explore their gender identity.

The most significant side effect of puberty blockers is decreased bone density.¹ As a result, providers typically do not prescribe these medications for more than 2-3 years. After discontinuation of the medication, bone density returns to baseline.¹ If the adolescent’s gender identity is marked and sustained over time, hormone therapy, such as testosterone or estrogen is then considered. Unlike puberty blockers, these medications can have permanent side effects. Testosterone use can lead to irreversible hair growth, alopecia, clitoromegaly, and voice deepening, while estrogen can cause permanent breast growth and halt sperm production.¹ Future fertility and these side effects are discussed with the patient in detail prior to the initiation of these medications.

Contrary to the current political narrative, gender-affirming care for children and adolescents is not taken lightly. These individuals often receive years of multidisciplinary assessments, with a focus on gender identity development, social development and support, and diagnostic assessment of possible co-occurring mental health or developmental concerns and capacity for decision making.¹ The clinical visits also occur with parental support and consent.

WPATH SOC8 also delineates the provider qualifications for health care professionals assessing these patients. Providers must be licensed by their statutory bodies and hold a postgraduate degree by a nationally accredited statutory institution; receive theoretical and evidence-based training and develop expertise in child, adolescent, and family mental health across the developmental spectrum; receive training and have expertise in gender identity development and gender diversity in children and adolescence; have the ability to assess capacity to assent/consent; receive training and develop expertise in autism spectrum disorders and other neurodevelopmental presentations; and to continue engaging in professional development in all areas relevant to gender-diverse children, adolescents, and families.¹

The most controversial aspect of gender-affirming care for children and adolescents relates to surgical treatment. While the rates of gender-affirming surgeries have increased for this age group over the years, the overall rate of gender-affirming surgery for adolescents is markedly lower compared with other adolescents seeking cosmetic surgeries and compared with transgender adults undergoing gender-affirming surgery.

In a cohort study conducted between 2016 to 2020, 48,019 patients were identified who had undergone gender-affirming surgery.² Only 3678 or 7.7% of patients were aged between 12 and 18, with the most common procedure being chest/breast surgery.² So, under about 1000 cases per year were gender-affirming surgeries on patients under 18.

During 2020 alone, the number of cisgender adolescents between the ages of 13 and 19 who underwent breast augmentation and breast reduction was 3233 and 4666, respectively.³ The outrage about gender-affirming surgeries on transgender youth, yet the silence on cosmetic procedures in this same age group, speaks volumes.

All surgeries on adolescents should be taken seriously and with caution, regardless of gender identity. However, current legislation disproportionately targets only transgender youth. For whatever reason, surgeries on transgender individuals are labeled as “body mutilation,” whereas surgeries on cisgender youth are not even discussed. Such inflammatory rhetoric and complete lack of empathy impedes the common goal of all parties: what is in the best interest of the minor? Unfortunately, in a few short months, the answer to this question will be determined by a group of nine justices who have no experience in medicine or transgender health care, instead of by medical experts and the parents who care for these individuals.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pennsylvania. She has no conflicts of interest.
 

References

1. Coleman E et al. Standards of care for the health of transgender and gender diverse people, version 8. Int J Transgender Health. 2022;23(sup):S1-S259.

2. Wright JD et al. National estimates of gender affirming surgery in the US. JAMA Netw Open. 2023 Aug 1;6(8):e2330348.

3. American Society of Plastic Surgeons. Plastic Surgery Statistics Report. ASPS National Clearinghouse of Plastic Surgery Procedural Statistics. 2020.

As Pride Month drew to a close, the Supreme Court made a shocking announcement. For the first time in the history of the court, it is willing to hear a legal challenge regarding gender-affirming care for minors. The justices will review whether a 2023 Tennessee law, SB1, which bans hormone therapy, puberty blockers, and surgery for transgender minors, is unconstitutional. This is the first time the Supreme Court will directly weigh in on gender-affirming care.

There are few topics as politically and medically divisive as gender-affirming care for minors. When the World Professional Association for Transgender Health (WPATH) released its updated Standards of Care, SOC8, one of the noticeable changes to the document was its approach to caring for transgender children and adolescents.

Dr. Brandt

Before I highlight these recommendations and the ensuing controversy, it is imperative to establish proper terminology. Unfortunately, medical and legal terms often differ. Both activists and opponents use these terms interchangeably, which makes discourse about an already emotionally charged topic extremely difficult. From a legal perspective, the terms “minor” and “child” often refer to individuals under the age of majority. In the United States, the age of majority is 18. However, the term child also has a well-established medical definition. A child is an individual between the stages of infancy and puberty. Adolescence is a transitional period marked by the onset of puberty until adulthood (typically the age of majority). As medical providers, understanding these definitions is essential to identifying misinformation pertaining to this type of healthcare.

For the purposes of this article, I will be adhering to the medical terminology. Now, I want to be very clear. WPATH does not endorse surgical procedures on children. Furthermore, surgeons are not performing gender-affirming surgeries on children. On adolescents, rarely. But children, never.

According to the updated SOC8, the only acceptable gender-affirming intervention for children is psychosocial support.¹ This does not include puberty blockers, hormones, or surgery, but rather allowing a child to explore their gender identity by experimenting with different clothing, toys, hairstyles, and even an alternative name that aligns more closely with their gender identity.¹

It is only after children reach adolescence that medical, and in rare cases, surgical interventions, can be considered. Puberty blockers are appropriate for patients who have started puberty and experience gender dysphoria. These medications are reversible, and their purpose is to temporarily pause puberty to allow the adolescent to further explore their gender identity.

The most significant side effect of puberty blockers is decreased bone density.¹ As a result, providers typically do not prescribe these medications for more than 2-3 years. After discontinuation of the medication, bone density returns to baseline.¹ If the adolescent’s gender identity is marked and sustained over time, hormone therapy, such as testosterone or estrogen is then considered. Unlike puberty blockers, these medications can have permanent side effects. Testosterone use can lead to irreversible hair growth, alopecia, clitoromegaly, and voice deepening, while estrogen can cause permanent breast growth and halt sperm production.¹ Future fertility and these side effects are discussed with the patient in detail prior to the initiation of these medications.

Contrary to the current political narrative, gender-affirming care for children and adolescents is not taken lightly. These individuals often receive years of multidisciplinary assessments, with a focus on gender identity development, social development and support, and diagnostic assessment of possible co-occurring mental health or developmental concerns and capacity for decision making.¹ The clinical visits also occur with parental support and consent.

WPATH SOC8 also delineates the provider qualifications for health care professionals assessing these patients. Providers must be licensed by their statutory bodies and hold a postgraduate degree by a nationally accredited statutory institution; receive theoretical and evidence-based training and develop expertise in child, adolescent, and family mental health across the developmental spectrum; receive training and have expertise in gender identity development and gender diversity in children and adolescence; have the ability to assess capacity to assent/consent; receive training and develop expertise in autism spectrum disorders and other neurodevelopmental presentations; and to continue engaging in professional development in all areas relevant to gender-diverse children, adolescents, and families.¹

The most controversial aspect of gender-affirming care for children and adolescents relates to surgical treatment. While the rates of gender-affirming surgeries have increased for this age group over the years, the overall rate of gender-affirming surgery for adolescents is markedly lower compared with other adolescents seeking cosmetic surgeries and compared with transgender adults undergoing gender-affirming surgery.

In a cohort study conducted between 2016 to 2020, 48,019 patients were identified who had undergone gender-affirming surgery.² Only 3678 or 7.7% of patients were aged between 12 and 18, with the most common procedure being chest/breast surgery.² So, under about 1000 cases per year were gender-affirming surgeries on patients under 18.

During 2020 alone, the number of cisgender adolescents between the ages of 13 and 19 who underwent breast augmentation and breast reduction was 3233 and 4666, respectively.³ The outrage about gender-affirming surgeries on transgender youth, yet the silence on cosmetic procedures in this same age group, speaks volumes.

All surgeries on adolescents should be taken seriously and with caution, regardless of gender identity. However, current legislation disproportionately targets only transgender youth. For whatever reason, surgeries on transgender individuals are labeled as “body mutilation,” whereas surgeries on cisgender youth are not even discussed. Such inflammatory rhetoric and complete lack of empathy impedes the common goal of all parties: what is in the best interest of the minor? Unfortunately, in a few short months, the answer to this question will be determined by a group of nine justices who have no experience in medicine or transgender health care, instead of by medical experts and the parents who care for these individuals.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pennsylvania. She has no conflicts of interest.
 

References

1. Coleman E et al. Standards of care for the health of transgender and gender diverse people, version 8. Int J Transgender Health. 2022;23(sup):S1-S259.

2. Wright JD et al. National estimates of gender affirming surgery in the US. JAMA Netw Open. 2023 Aug 1;6(8):e2330348.

3. American Society of Plastic Surgeons. Plastic Surgery Statistics Report. ASPS National Clearinghouse of Plastic Surgery Procedural Statistics. 2020.

As Pride Month drew to a close, the Supreme Court made a shocking announcement. For the first time in the history of the court, it is willing to hear a legal challenge regarding gender-affirming care for minors. The justices will review whether a 2023 Tennessee law, SB1, which bans hormone therapy, puberty blockers, and surgery for transgender minors, is unconstitutional. This is the first time the Supreme Court will directly weigh in on gender-affirming care.

There are few topics as politically and medically divisive as gender-affirming care for minors. When the World Professional Association for Transgender Health (WPATH) released its updated Standards of Care, SOC8, one of the noticeable changes to the document was its approach to caring for transgender children and adolescents.

Dr. Brandt

Before I highlight these recommendations and the ensuing controversy, it is imperative to establish proper terminology. Unfortunately, medical and legal terms often differ. Both activists and opponents use these terms interchangeably, which makes discourse about an already emotionally charged topic extremely difficult. From a legal perspective, the terms “minor” and “child” often refer to individuals under the age of majority. In the United States, the age of majority is 18. However, the term child also has a well-established medical definition. A child is an individual between the stages of infancy and puberty. Adolescence is a transitional period marked by the onset of puberty until adulthood (typically the age of majority). As medical providers, understanding these definitions is essential to identifying misinformation pertaining to this type of healthcare.

For the purposes of this article, I will be adhering to the medical terminology. Now, I want to be very clear. WPATH does not endorse surgical procedures on children. Furthermore, surgeons are not performing gender-affirming surgeries on children. On adolescents, rarely. But children, never.

According to the updated SOC8, the only acceptable gender-affirming intervention for children is psychosocial support.¹ This does not include puberty blockers, hormones, or surgery, but rather allowing a child to explore their gender identity by experimenting with different clothing, toys, hairstyles, and even an alternative name that aligns more closely with their gender identity.¹

It is only after children reach adolescence that medical, and in rare cases, surgical interventions, can be considered. Puberty blockers are appropriate for patients who have started puberty and experience gender dysphoria. These medications are reversible, and their purpose is to temporarily pause puberty to allow the adolescent to further explore their gender identity.

The most significant side effect of puberty blockers is decreased bone density.¹ As a result, providers typically do not prescribe these medications for more than 2-3 years. After discontinuation of the medication, bone density returns to baseline.¹ If the adolescent’s gender identity is marked and sustained over time, hormone therapy, such as testosterone or estrogen is then considered. Unlike puberty blockers, these medications can have permanent side effects. Testosterone use can lead to irreversible hair growth, alopecia, clitoromegaly, and voice deepening, while estrogen can cause permanent breast growth and halt sperm production.¹ Future fertility and these side effects are discussed with the patient in detail prior to the initiation of these medications.

Contrary to the current political narrative, gender-affirming care for children and adolescents is not taken lightly. These individuals often receive years of multidisciplinary assessments, with a focus on gender identity development, social development and support, and diagnostic assessment of possible co-occurring mental health or developmental concerns and capacity for decision making.¹ The clinical visits also occur with parental support and consent.

WPATH SOC8 also delineates the provider qualifications for health care professionals assessing these patients. Providers must be licensed by their statutory bodies and hold a postgraduate degree by a nationally accredited statutory institution; receive theoretical and evidence-based training and develop expertise in child, adolescent, and family mental health across the developmental spectrum; receive training and have expertise in gender identity development and gender diversity in children and adolescence; have the ability to assess capacity to assent/consent; receive training and develop expertise in autism spectrum disorders and other neurodevelopmental presentations; and to continue engaging in professional development in all areas relevant to gender-diverse children, adolescents, and families.¹

The most controversial aspect of gender-affirming care for children and adolescents relates to surgical treatment. While the rates of gender-affirming surgeries have increased for this age group over the years, the overall rate of gender-affirming surgery for adolescents is markedly lower compared with other adolescents seeking cosmetic surgeries and compared with transgender adults undergoing gender-affirming surgery.

In a cohort study conducted between 2016 to 2020, 48,019 patients were identified who had undergone gender-affirming surgery.² Only 3678 or 7.7% of patients were aged between 12 and 18, with the most common procedure being chest/breast surgery.² So, under about 1000 cases per year were gender-affirming surgeries on patients under 18.

During 2020 alone, the number of cisgender adolescents between the ages of 13 and 19 who underwent breast augmentation and breast reduction was 3233 and 4666, respectively.³ The outrage about gender-affirming surgeries on transgender youth, yet the silence on cosmetic procedures in this same age group, speaks volumes.

All surgeries on adolescents should be taken seriously and with caution, regardless of gender identity. However, current legislation disproportionately targets only transgender youth. For whatever reason, surgeries on transgender individuals are labeled as “body mutilation,” whereas surgeries on cisgender youth are not even discussed. Such inflammatory rhetoric and complete lack of empathy impedes the common goal of all parties: what is in the best interest of the minor? Unfortunately, in a few short months, the answer to this question will be determined by a group of nine justices who have no experience in medicine or transgender health care, instead of by medical experts and the parents who care for these individuals.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pennsylvania. She has no conflicts of interest.
 

References

1. Coleman E et al. Standards of care for the health of transgender and gender diverse people, version 8. Int J Transgender Health. 2022;23(sup):S1-S259.

2. Wright JD et al. National estimates of gender affirming surgery in the US. JAMA Netw Open. 2023 Aug 1;6(8):e2330348.

3. American Society of Plastic Surgeons. Plastic Surgery Statistics Report. ASPS National Clearinghouse of Plastic Surgery Procedural Statistics. 2020.

Recent research on popular weight loss drugs has uncovered surprising benefits beyond their intended use, like lowering the risk of fatal heart attacks. And now there may be another unforeseen advantage: People with type 2 diabetes who took these drugs had a lower risk of having 10 out of 13 obesity-related cancers, compared to those who used insulin therapy.

That’s according to a study published July 5 in JAMA Network Open where researchers studied glucagon-like peptide receptor agonists (known as GLP-1RAs), a class of drugs used to treat diabetes and obesity. Ozempic, Wegovy, Mounjaro, and Zepbound, which have become well-known recently because they are linked to rapid weight loss, contain GLP-1RAs.

For the study, they looked at electronic health records of 1.7 million patients who had type 2 diabetes, no prior diagnosis of obesity-related cancers, and had been prescribed GLP-1RAs, insulins, or metformin from March 2005 to November 2018.

The scientists found that compared to patients who took insulin, people who took GLP-1RAs had a “significant risk reduction” in 10 of 13 obesity-related cancers. Those 10 cancers were esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma.

Compared with patients taking insulin, patients taking GLP-1RAs showed no statistically significant reduction in stomach cancer and no reduced risk of breast and thyroid cancers, the study said.

But the study found no decrease in cancer risk with GLP-1RAs compared with metformin.

While the study results suggest that these drugs may reduce the risk of certain obesity-related cancers better than insulins, more research is needed, they said.

A version of this article appeared on WebMD.com.

Recent research on popular weight loss drugs has uncovered surprising benefits beyond their intended use, like lowering the risk of fatal heart attacks. And now there may be another unforeseen advantage: People with type 2 diabetes who took these drugs had a lower risk of having 10 out of 13 obesity-related cancers, compared to those who used insulin therapy.

That’s according to a study published July 5 in JAMA Network Open where researchers studied glucagon-like peptide receptor agonists (known as GLP-1RAs), a class of drugs used to treat diabetes and obesity. Ozempic, Wegovy, Mounjaro, and Zepbound, which have become well-known recently because they are linked to rapid weight loss, contain GLP-1RAs.

For the study, they looked at electronic health records of 1.7 million patients who had type 2 diabetes, no prior diagnosis of obesity-related cancers, and had been prescribed GLP-1RAs, insulins, or metformin from March 2005 to November 2018.

The scientists found that compared to patients who took insulin, people who took GLP-1RAs had a “significant risk reduction” in 10 of 13 obesity-related cancers. Those 10 cancers were esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma.

Compared with patients taking insulin, patients taking GLP-1RAs showed no statistically significant reduction in stomach cancer and no reduced risk of breast and thyroid cancers, the study said.

But the study found no decrease in cancer risk with GLP-1RAs compared with metformin.

While the study results suggest that these drugs may reduce the risk of certain obesity-related cancers better than insulins, more research is needed, they said.

A version of this article appeared on WebMD.com.

Recent research on popular weight loss drugs has uncovered surprising benefits beyond their intended use, like lowering the risk of fatal heart attacks. And now there may be another unforeseen advantage: People with type 2 diabetes who took these drugs had a lower risk of having 10 out of 13 obesity-related cancers, compared to those who used insulin therapy.

That’s according to a study published July 5 in JAMA Network Open where researchers studied glucagon-like peptide receptor agonists (known as GLP-1RAs), a class of drugs used to treat diabetes and obesity. Ozempic, Wegovy, Mounjaro, and Zepbound, which have become well-known recently because they are linked to rapid weight loss, contain GLP-1RAs.

For the study, they looked at electronic health records of 1.7 million patients who had type 2 diabetes, no prior diagnosis of obesity-related cancers, and had been prescribed GLP-1RAs, insulins, or metformin from March 2005 to November 2018.

The scientists found that compared to patients who took insulin, people who took GLP-1RAs had a “significant risk reduction” in 10 of 13 obesity-related cancers. Those 10 cancers were esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma.

Compared with patients taking insulin, patients taking GLP-1RAs showed no statistically significant reduction in stomach cancer and no reduced risk of breast and thyroid cancers, the study said.

But the study found no decrease in cancer risk with GLP-1RAs compared with metformin.

While the study results suggest that these drugs may reduce the risk of certain obesity-related cancers better than insulins, more research is needed, they said.

A version of this article appeared on WebMD.com.

Mount Sinai Health System in New York City is forcing part-time physicians to sign employment contracts that violate their labor rights, according to a June 2024 complaint by the National Labor Relations Board (NLRB). 

The complaint stems from no-poaching and confidentiality clauses in the agreements required as a condition of employment, NLRB officials alleged.

The contracts state that, for 1 year following termination, part-time physicians may not recruit, solicit, or induce to terminate the employment of any hospital system employee or independent contractor, according to a copy of the terms included in NLRB’s June 18 complaint. 

By requiring the agreements, NLRB officials claimed, Mount Sinai is “interfering with, restraining, and coercing employees” in violation of the National Labor Relations Act. The health system’s “unfair labor practices” affects commerce as outlined under the law, according to the NLRB. The Act bans employers from burdening or obstructing commerce or the free flow of commerce.

Mount Sinai did not respond to requests for comment.

The NLRB’s complaint follows a landmark decision by the Federal Trade Commission (FTC) to ban noncompete agreements nationwide. In April 2024, the FTC voted to prohibit noncompetes indefinitely in an effort to protect workers.

“Noncompete clauses keep wages low, suppress new ideas, and rob the American economy of dynamism, including from the more than 8500 new startups that would be created a year once noncompetes are banned,” FTC Chair Lina M. Khan said in a statement. “The FTC’s final rule to ban noncompetes will ensure Americans have the freedom to pursue a new job, start a new business, or bring a new idea to market.”

Business groups and agencies have since sued to challenge against the ban, including the Chamber of Commerce. The Chamber and other business groups argue that noncompete agreements are important for companies to protect trade secrets, shield recruiting investments, and hide confidential information. The lawsuits are ongoing. 
 

A Physician Blows the Whistle

An anonymous physician first alerted the NLRB to the contract language in November 2023. The doctor was required the sign the hospital system’s agreement for part-time physicians. The complaint does not say if the employee is still employed by the hospital system. 

To remedy the unfair labor practices alleged, the NLRB seeks an order requiring the health system to rescind the contract language, stop any actions against current or former employees to enforce the provisions, and make whole any employees who suffered financial losses related to the contract terms. 

The allegation against Mount Sinai is among a rising number of grievances filed with the NLRB that claim unfair labor practices. During the first 6 months of fiscal year 2024, unfair labor practice charges filed across the NLRB’s field offices increased 7% — from 9612 in 2023 to 10,278 in 2024, according to a news release. 

NLRB, meanwhile has been cracking down on anticompetitive labor practices and confidentiality provisions that prevent employees from speaking out. 

In a February 2023 decision for instance, NLRB ruled that an employer violates the National Labor Relations Act by offering severance agreements to workers that include restrictive confidentiality and nondisparagement terms. In 2022, the NLRB and the Federal Trade Commission forged a partnership to more widely combat unfair, anticompetitive, and deceptive business practices. 

“Noncompete provisions reasonably tend to chill employees in the exercise of Section 7 rights when the provisions could reasonably be construed by employees to deny them the ability to quit or change jobs by cutting off their access to other employment opportunities that they are qualified for,” NLRB General Counsel Jennifer Abruzzo said in a 2023 release. 

Ms. Abruzzo stressed in a memo that NLR Act is committed to an interagency approach to restrictions on the exercise of employee rights, “including limits to workers’ job mobility, information sharing, and referrals to other agencies.” 

Mount Sinai Health System must respond to the NLRB’s complaint by July 16, and an administrative law judge is scheduled to hear the case on September 24.

A version of this article first appeared on Medscape.com.

Mount Sinai Health System in New York City is forcing part-time physicians to sign employment contracts that violate their labor rights, according to a June 2024 complaint by the National Labor Relations Board (NLRB). 

The complaint stems from no-poaching and confidentiality clauses in the agreements required as a condition of employment, NLRB officials alleged.

The contracts state that, for 1 year following termination, part-time physicians may not recruit, solicit, or induce to terminate the employment of any hospital system employee or independent contractor, according to a copy of the terms included in NLRB’s June 18 complaint. 

By requiring the agreements, NLRB officials claimed, Mount Sinai is “interfering with, restraining, and coercing employees” in violation of the National Labor Relations Act. The health system’s “unfair labor practices” affects commerce as outlined under the law, according to the NLRB. The Act bans employers from burdening or obstructing commerce or the free flow of commerce.

Mount Sinai did not respond to requests for comment.

The NLRB’s complaint follows a landmark decision by the Federal Trade Commission (FTC) to ban noncompete agreements nationwide. In April 2024, the FTC voted to prohibit noncompetes indefinitely in an effort to protect workers.

“Noncompete clauses keep wages low, suppress new ideas, and rob the American economy of dynamism, including from the more than 8500 new startups that would be created a year once noncompetes are banned,” FTC Chair Lina M. Khan said in a statement. “The FTC’s final rule to ban noncompetes will ensure Americans have the freedom to pursue a new job, start a new business, or bring a new idea to market.”

Business groups and agencies have since sued to challenge against the ban, including the Chamber of Commerce. The Chamber and other business groups argue that noncompete agreements are important for companies to protect trade secrets, shield recruiting investments, and hide confidential information. The lawsuits are ongoing. 
 

A Physician Blows the Whistle

An anonymous physician first alerted the NLRB to the contract language in November 2023. The doctor was required the sign the hospital system’s agreement for part-time physicians. The complaint does not say if the employee is still employed by the hospital system. 

To remedy the unfair labor practices alleged, the NLRB seeks an order requiring the health system to rescind the contract language, stop any actions against current or former employees to enforce the provisions, and make whole any employees who suffered financial losses related to the contract terms. 

The allegation against Mount Sinai is among a rising number of grievances filed with the NLRB that claim unfair labor practices. During the first 6 months of fiscal year 2024, unfair labor practice charges filed across the NLRB’s field offices increased 7% — from 9612 in 2023 to 10,278 in 2024, according to a news release. 

NLRB, meanwhile has been cracking down on anticompetitive labor practices and confidentiality provisions that prevent employees from speaking out. 

In a February 2023 decision for instance, NLRB ruled that an employer violates the National Labor Relations Act by offering severance agreements to workers that include restrictive confidentiality and nondisparagement terms. In 2022, the NLRB and the Federal Trade Commission forged a partnership to more widely combat unfair, anticompetitive, and deceptive business practices. 

“Noncompete provisions reasonably tend to chill employees in the exercise of Section 7 rights when the provisions could reasonably be construed by employees to deny them the ability to quit or change jobs by cutting off their access to other employment opportunities that they are qualified for,” NLRB General Counsel Jennifer Abruzzo said in a 2023 release. 

Ms. Abruzzo stressed in a memo that NLR Act is committed to an interagency approach to restrictions on the exercise of employee rights, “including limits to workers’ job mobility, information sharing, and referrals to other agencies.” 

Mount Sinai Health System must respond to the NLRB’s complaint by July 16, and an administrative law judge is scheduled to hear the case on September 24.

A version of this article first appeared on Medscape.com.

Mount Sinai Health System in New York City is forcing part-time physicians to sign employment contracts that violate their labor rights, according to a June 2024 complaint by the National Labor Relations Board (NLRB). 

The complaint stems from no-poaching and confidentiality clauses in the agreements required as a condition of employment, NLRB officials alleged.

The contracts state that, for 1 year following termination, part-time physicians may not recruit, solicit, or induce to terminate the employment of any hospital system employee or independent contractor, according to a copy of the terms included in NLRB’s June 18 complaint. 

By requiring the agreements, NLRB officials claimed, Mount Sinai is “interfering with, restraining, and coercing employees” in violation of the National Labor Relations Act. The health system’s “unfair labor practices” affects commerce as outlined under the law, according to the NLRB. The Act bans employers from burdening or obstructing commerce or the free flow of commerce.

Mount Sinai did not respond to requests for comment.

The NLRB’s complaint follows a landmark decision by the Federal Trade Commission (FTC) to ban noncompete agreements nationwide. In April 2024, the FTC voted to prohibit noncompetes indefinitely in an effort to protect workers.

“Noncompete clauses keep wages low, suppress new ideas, and rob the American economy of dynamism, including from the more than 8500 new startups that would be created a year once noncompetes are banned,” FTC Chair Lina M. Khan said in a statement. “The FTC’s final rule to ban noncompetes will ensure Americans have the freedom to pursue a new job, start a new business, or bring a new idea to market.”

Business groups and agencies have since sued to challenge against the ban, including the Chamber of Commerce. The Chamber and other business groups argue that noncompete agreements are important for companies to protect trade secrets, shield recruiting investments, and hide confidential information. The lawsuits are ongoing. 
 

A Physician Blows the Whistle

An anonymous physician first alerted the NLRB to the contract language in November 2023. The doctor was required the sign the hospital system’s agreement for part-time physicians. The complaint does not say if the employee is still employed by the hospital system. 

To remedy the unfair labor practices alleged, the NLRB seeks an order requiring the health system to rescind the contract language, stop any actions against current or former employees to enforce the provisions, and make whole any employees who suffered financial losses related to the contract terms. 

The allegation against Mount Sinai is among a rising number of grievances filed with the NLRB that claim unfair labor practices. During the first 6 months of fiscal year 2024, unfair labor practice charges filed across the NLRB’s field offices increased 7% — from 9612 in 2023 to 10,278 in 2024, according to a news release. 

NLRB, meanwhile has been cracking down on anticompetitive labor practices and confidentiality provisions that prevent employees from speaking out. 

In a February 2023 decision for instance, NLRB ruled that an employer violates the National Labor Relations Act by offering severance agreements to workers that include restrictive confidentiality and nondisparagement terms. In 2022, the NLRB and the Federal Trade Commission forged a partnership to more widely combat unfair, anticompetitive, and deceptive business practices. 

“Noncompete provisions reasonably tend to chill employees in the exercise of Section 7 rights when the provisions could reasonably be construed by employees to deny them the ability to quit or change jobs by cutting off their access to other employment opportunities that they are qualified for,” NLRB General Counsel Jennifer Abruzzo said in a 2023 release. 

Ms. Abruzzo stressed in a memo that NLR Act is committed to an interagency approach to restrictions on the exercise of employee rights, “including limits to workers’ job mobility, information sharing, and referrals to other agencies.” 

Mount Sinai Health System must respond to the NLRB’s complaint by July 16, and an administrative law judge is scheduled to hear the case on September 24.

A version of this article first appeared on Medscape.com.

Patients with early, triple negative breast cancer (TNBC) and high risk of recurrence after initial therapy had significantly better 3-year overall survival (OS) when given adjuvant avelumab compared with those who were observed without further treatment, in the A-BRAVE trial.

“The 30% reduction in the risk of distant metastasis, and 34% reduction in the risk of death suggests that avelumab may have a role in early triple negative breast cancer patients at high risk of relapse after primary surgery or with invasive residual disease after neoadjuvant chemotherapy,” Pierfranco Conte, MD, from the department of surgery, oncology, and gastroenterology at the University of Padua, Italy, reported at the annual meeting of the American Society of Clinical Oncology.

A-BRAVE is the first randomized phase 3 trial patients with TNBC, treated with adjuvant avelumab, explained Dr. Conte. “Neoadjuvant chemotherapy is recommended for stage cT1c or larger, or cN+ disease. However, in case of invasive residual disease at surgery, prognosis is still very poor.”

TNBC is more immunogenic compared with other breast cancer subtypes, suggesting a role for immune checkpoint inhibitors such as avelumab in this setting, he said.
 

A-BRAVE Methods and Results

The trial enrolled 477 patients, median age 51 years, between June 2016 and October 2020, after their disease had progressed following initial treatment. There were two strata of patients: those who had received upfront surgery and then adjuvant chemotherapy before disease progression (stratum A, 18%); and those who received neoadjuvant chemotherapy, surgery, and then adjuvant chemo, but still had residual disease (stratum B, 82%).

Patients were randomized to either observation (n = 239) or treatment with avelumab (n = 238), at a dose of 10 mg/kg every 2 weeks for one year.

At a median follow-up of 52.1 months, avelumab did not show an advantage for the primary endpoint of 3-year disease-free survival (DFS), with 68.3% of treated patients meeting this endpoint, compared to 63.2% of observed patients (hazard ratio [HR 0.81, P = .172].

However, the treatment did show statistically significant benefits for the secondary 3-year OS endpoint (84.8% vs 76.3%, HR 0.66, P = .035).

“Trying to understand why we did observe a greater benefit with avelumab in overall survival compared to disease-free survival, we also made a post-hoc exploratory analysis on distant disease-free survival,” explained Dr. Conte.

There was a statistically significant 3-year distant disease-free survival (DDFS) benefit for treated patients compared with controls (75.4% vs 67.9%, HR 0.7, P = .0277), translating to a 30% reduction in the risk of distant metastasis, he noted.
 

Findings Are ‘Hypothesis-Generating’

The results are “hypothesis-generating at this point,” Alexandra Thomas, MD, a breast medical oncologist who was not involved in the research, said in an interview. “These results suggest that the story on how to best utilize checkpoint blockade as adjuvant therapy in triple negative breast cancer may not yet be fully written.”

She emphasized the study did not meet its primary endpoint, “though the results for secondary endpoints OS and the exploratory endpoint DDFS are intriguing.

“A-BRAVE is a smaller study, especially relative to Impassion030 (ALEXANDRA), which enrolled over 2,000 patients,” she explained. “It is notable that avelumab has slightly different properties than atezolizumab, which was used in Impassion030.”

“Avelumab is also a weak PD-L2 inhibitor. Could this be important? Notably, today most patients with clinical stage II-III triple negative breast cancer will receive pembrolizumab as per KEYNOTE-522, so the potential for clinical impact is greatly reduced,” added Dr. Thomas, professor and assistant director in the department of internal medicine at Duke Cancer Institute, in Durham, North Carolina.

SWOG1814, which has not been reported yet, “also looks at pembrolizumab in patients with residual disease post neoadjuvant chemotherapy and will provide further important information on in this space,” she said.

Merck KGaA funded the study.

Dr. Conte disclosed consulting or advisory roles with Daiichi Sankyo/Lilly, Gilead Sciences, Reveal Genomics; a HER2Dx patient; and providing expert testimony for AstraZeneca.

Dr. Thomas disclosed research grants from Sanofi and Merck.

Patients with early, triple negative breast cancer (TNBC) and high risk of recurrence after initial therapy had significantly better 3-year overall survival (OS) when given adjuvant avelumab compared with those who were observed without further treatment, in the A-BRAVE trial.

“The 30% reduction in the risk of distant metastasis, and 34% reduction in the risk of death suggests that avelumab may have a role in early triple negative breast cancer patients at high risk of relapse after primary surgery or with invasive residual disease after neoadjuvant chemotherapy,” Pierfranco Conte, MD, from the department of surgery, oncology, and gastroenterology at the University of Padua, Italy, reported at the annual meeting of the American Society of Clinical Oncology.

A-BRAVE is the first randomized phase 3 trial patients with TNBC, treated with adjuvant avelumab, explained Dr. Conte. “Neoadjuvant chemotherapy is recommended for stage cT1c or larger, or cN+ disease. However, in case of invasive residual disease at surgery, prognosis is still very poor.”

TNBC is more immunogenic compared with other breast cancer subtypes, suggesting a role for immune checkpoint inhibitors such as avelumab in this setting, he said.
 

A-BRAVE Methods and Results

The trial enrolled 477 patients, median age 51 years, between June 2016 and October 2020, after their disease had progressed following initial treatment. There were two strata of patients: those who had received upfront surgery and then adjuvant chemotherapy before disease progression (stratum A, 18%); and those who received neoadjuvant chemotherapy, surgery, and then adjuvant chemo, but still had residual disease (stratum B, 82%).

Patients were randomized to either observation (n = 239) or treatment with avelumab (n = 238), at a dose of 10 mg/kg every 2 weeks for one year.

At a median follow-up of 52.1 months, avelumab did not show an advantage for the primary endpoint of 3-year disease-free survival (DFS), with 68.3% of treated patients meeting this endpoint, compared to 63.2% of observed patients (hazard ratio [HR 0.81, P = .172].

However, the treatment did show statistically significant benefits for the secondary 3-year OS endpoint (84.8% vs 76.3%, HR 0.66, P = .035).

“Trying to understand why we did observe a greater benefit with avelumab in overall survival compared to disease-free survival, we also made a post-hoc exploratory analysis on distant disease-free survival,” explained Dr. Conte.

There was a statistically significant 3-year distant disease-free survival (DDFS) benefit for treated patients compared with controls (75.4% vs 67.9%, HR 0.7, P = .0277), translating to a 30% reduction in the risk of distant metastasis, he noted.
 

Findings Are ‘Hypothesis-Generating’

The results are “hypothesis-generating at this point,” Alexandra Thomas, MD, a breast medical oncologist who was not involved in the research, said in an interview. “These results suggest that the story on how to best utilize checkpoint blockade as adjuvant therapy in triple negative breast cancer may not yet be fully written.”

She emphasized the study did not meet its primary endpoint, “though the results for secondary endpoints OS and the exploratory endpoint DDFS are intriguing.

“A-BRAVE is a smaller study, especially relative to Impassion030 (ALEXANDRA), which enrolled over 2,000 patients,” she explained. “It is notable that avelumab has slightly different properties than atezolizumab, which was used in Impassion030.”

“Avelumab is also a weak PD-L2 inhibitor. Could this be important? Notably, today most patients with clinical stage II-III triple negative breast cancer will receive pembrolizumab as per KEYNOTE-522, so the potential for clinical impact is greatly reduced,” added Dr. Thomas, professor and assistant director in the department of internal medicine at Duke Cancer Institute, in Durham, North Carolina.

SWOG1814, which has not been reported yet, “also looks at pembrolizumab in patients with residual disease post neoadjuvant chemotherapy and will provide further important information on in this space,” she said.

Merck KGaA funded the study.

Dr. Conte disclosed consulting or advisory roles with Daiichi Sankyo/Lilly, Gilead Sciences, Reveal Genomics; a HER2Dx patient; and providing expert testimony for AstraZeneca.

Dr. Thomas disclosed research grants from Sanofi and Merck.

Patients with early, triple negative breast cancer (TNBC) and high risk of recurrence after initial therapy had significantly better 3-year overall survival (OS) when given adjuvant avelumab compared with those who were observed without further treatment, in the A-BRAVE trial.

“The 30% reduction in the risk of distant metastasis, and 34% reduction in the risk of death suggests that avelumab may have a role in early triple negative breast cancer patients at high risk of relapse after primary surgery or with invasive residual disease after neoadjuvant chemotherapy,” Pierfranco Conte, MD, from the department of surgery, oncology, and gastroenterology at the University of Padua, Italy, reported at the annual meeting of the American Society of Clinical Oncology.

A-BRAVE is the first randomized phase 3 trial patients with TNBC, treated with adjuvant avelumab, explained Dr. Conte. “Neoadjuvant chemotherapy is recommended for stage cT1c or larger, or cN+ disease. However, in case of invasive residual disease at surgery, prognosis is still very poor.”

TNBC is more immunogenic compared with other breast cancer subtypes, suggesting a role for immune checkpoint inhibitors such as avelumab in this setting, he said.
 

A-BRAVE Methods and Results

The trial enrolled 477 patients, median age 51 years, between June 2016 and October 2020, after their disease had progressed following initial treatment. There were two strata of patients: those who had received upfront surgery and then adjuvant chemotherapy before disease progression (stratum A, 18%); and those who received neoadjuvant chemotherapy, surgery, and then adjuvant chemo, but still had residual disease (stratum B, 82%).

Patients were randomized to either observation (n = 239) or treatment with avelumab (n = 238), at a dose of 10 mg/kg every 2 weeks for one year.

At a median follow-up of 52.1 months, avelumab did not show an advantage for the primary endpoint of 3-year disease-free survival (DFS), with 68.3% of treated patients meeting this endpoint, compared to 63.2% of observed patients (hazard ratio [HR 0.81, P = .172].

However, the treatment did show statistically significant benefits for the secondary 3-year OS endpoint (84.8% vs 76.3%, HR 0.66, P = .035).

“Trying to understand why we did observe a greater benefit with avelumab in overall survival compared to disease-free survival, we also made a post-hoc exploratory analysis on distant disease-free survival,” explained Dr. Conte.

There was a statistically significant 3-year distant disease-free survival (DDFS) benefit for treated patients compared with controls (75.4% vs 67.9%, HR 0.7, P = .0277), translating to a 30% reduction in the risk of distant metastasis, he noted.
 

Findings Are ‘Hypothesis-Generating’

The results are “hypothesis-generating at this point,” Alexandra Thomas, MD, a breast medical oncologist who was not involved in the research, said in an interview. “These results suggest that the story on how to best utilize checkpoint blockade as adjuvant therapy in triple negative breast cancer may not yet be fully written.”

She emphasized the study did not meet its primary endpoint, “though the results for secondary endpoints OS and the exploratory endpoint DDFS are intriguing.

“A-BRAVE is a smaller study, especially relative to Impassion030 (ALEXANDRA), which enrolled over 2,000 patients,” she explained. “It is notable that avelumab has slightly different properties than atezolizumab, which was used in Impassion030.”

“Avelumab is also a weak PD-L2 inhibitor. Could this be important? Notably, today most patients with clinical stage II-III triple negative breast cancer will receive pembrolizumab as per KEYNOTE-522, so the potential for clinical impact is greatly reduced,” added Dr. Thomas, professor and assistant director in the department of internal medicine at Duke Cancer Institute, in Durham, North Carolina.

SWOG1814, which has not been reported yet, “also looks at pembrolizumab in patients with residual disease post neoadjuvant chemotherapy and will provide further important information on in this space,” she said.

Merck KGaA funded the study.

Dr. Conte disclosed consulting or advisory roles with Daiichi Sankyo/Lilly, Gilead Sciences, Reveal Genomics; a HER2Dx patient; and providing expert testimony for AstraZeneca.

Dr. Thomas disclosed research grants from Sanofi and Merck.

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

TOPLINE:

Compared with the general population, patients with urticaria had a 49% higher risk of developing cancer in the first year following diagnosis, which decreased to 6% in subsequent years, in a cohort study using Danish healthcare databases.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from Danish healthcare registries and compared the incident cancer risk between patients with urticaria and the risk in the general population.
• They identified 87,507 patients (58% women) with a primary or secondary first-time hospital outpatient clinic, emergency room, or inpatient diagnosis of urticaria between 1980 and 2022, who were followed for a median of 10.1 years.
• Incident cancers, including nonmelanoma skin cancer, were identified using the Danish Cancer Registry and classified by the extent of spread at the time of diagnosis.
• This study computed the absolute cancer risk within the first year of an urticaria diagnosis and standardized incidence ratios (SIRs), with 95% CIs standardized to Danish national cancer rates.

TAKEAWAY:

• For the first year of follow-up, the absolute risk for all cancer types was 0.7%, and it was 29.5% for subsequent years. The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11), which was based on 7788 observed cancer cases compared with 7161 cases expected over the entire follow-up period.
• Within the first year of follow-up, 588 patients with urticaria were diagnosed with cancer, for an SIR of 1.49 (95% CI, 1.38-1.62) for all cancer types.
• After the first year, the SIR for all cancer sites decreased and stabilized at 1.06 (95% CI, 1.04-1.09), with 7200 observed cancer cases.
• The risk was highest for hematological cancers in the first year, particularly Hodgkin lymphoma (SIR, 5.35; 95% CI, 2.56-9.85).

IN PRACTICE:

“Our study suggests that urticaria may be a marker of occult cancer and that it is associated with a slightly increased long-term cancer risk,” the authors wrote.

SOURCE:

The study was led by Sissel B.T. Sørensen, departments of dermatology and rheumatology, Aarhus University Hospital, Aarhus, Denmark. It was published online on June 27, 2024, in the British Journal of Dermatology.

LIMITATIONS:

The study is limited by its observational design and reliance on registry data, which may be subject to misclassification or incomplete information. In addition, the study could not assess individual patient factors such as lifestyle or genetic predispositions that may influence cancer risk, and the results may not be generalizable to other populations. Finally, the exact biologic mechanisms linking urticaria and cancer remain unclear, warranting further investigation.

DISCLOSURES:

The study did not receive any funding. The authors reported that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Compared with the general population, patients with urticaria had a 49% higher risk of developing cancer in the first year following diagnosis, which decreased to 6% in subsequent years, in a cohort study using Danish healthcare databases.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from Danish healthcare registries and compared the incident cancer risk between patients with urticaria and the risk in the general population.
• They identified 87,507 patients (58% women) with a primary or secondary first-time hospital outpatient clinic, emergency room, or inpatient diagnosis of urticaria between 1980 and 2022, who were followed for a median of 10.1 years.
• Incident cancers, including nonmelanoma skin cancer, were identified using the Danish Cancer Registry and classified by the extent of spread at the time of diagnosis.
• This study computed the absolute cancer risk within the first year of an urticaria diagnosis and standardized incidence ratios (SIRs), with 95% CIs standardized to Danish national cancer rates.

TAKEAWAY:

• For the first year of follow-up, the absolute risk for all cancer types was 0.7%, and it was 29.5% for subsequent years. The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11), which was based on 7788 observed cancer cases compared with 7161 cases expected over the entire follow-up period.
• Within the first year of follow-up, 588 patients with urticaria were diagnosed with cancer, for an SIR of 1.49 (95% CI, 1.38-1.62) for all cancer types.
• After the first year, the SIR for all cancer sites decreased and stabilized at 1.06 (95% CI, 1.04-1.09), with 7200 observed cancer cases.
• The risk was highest for hematological cancers in the first year, particularly Hodgkin lymphoma (SIR, 5.35; 95% CI, 2.56-9.85).

IN PRACTICE:

“Our study suggests that urticaria may be a marker of occult cancer and that it is associated with a slightly increased long-term cancer risk,” the authors wrote.

SOURCE:

The study was led by Sissel B.T. Sørensen, departments of dermatology and rheumatology, Aarhus University Hospital, Aarhus, Denmark. It was published online on June 27, 2024, in the British Journal of Dermatology.

LIMITATIONS:

The study is limited by its observational design and reliance on registry data, which may be subject to misclassification or incomplete information. In addition, the study could not assess individual patient factors such as lifestyle or genetic predispositions that may influence cancer risk, and the results may not be generalizable to other populations. Finally, the exact biologic mechanisms linking urticaria and cancer remain unclear, warranting further investigation.

DISCLOSURES:

The study did not receive any funding. The authors reported that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Compared with the general population, patients with urticaria had a 49% higher risk of developing cancer in the first year following diagnosis, which decreased to 6% in subsequent years, in a cohort study using Danish healthcare databases.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from Danish healthcare registries and compared the incident cancer risk between patients with urticaria and the risk in the general population.
• They identified 87,507 patients (58% women) with a primary or secondary first-time hospital outpatient clinic, emergency room, or inpatient diagnosis of urticaria between 1980 and 2022, who were followed for a median of 10.1 years.
• Incident cancers, including nonmelanoma skin cancer, were identified using the Danish Cancer Registry and classified by the extent of spread at the time of diagnosis.
• This study computed the absolute cancer risk within the first year of an urticaria diagnosis and standardized incidence ratios (SIRs), with 95% CIs standardized to Danish national cancer rates.

TAKEAWAY:

• For the first year of follow-up, the absolute risk for all cancer types was 0.7%, and it was 29.5% for subsequent years. The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11), which was based on 7788 observed cancer cases compared with 7161 cases expected over the entire follow-up period.
• Within the first year of follow-up, 588 patients with urticaria were diagnosed with cancer, for an SIR of 1.49 (95% CI, 1.38-1.62) for all cancer types.
• After the first year, the SIR for all cancer sites decreased and stabilized at 1.06 (95% CI, 1.04-1.09), with 7200 observed cancer cases.
• The risk was highest for hematological cancers in the first year, particularly Hodgkin lymphoma (SIR, 5.35; 95% CI, 2.56-9.85).

IN PRACTICE:

“Our study suggests that urticaria may be a marker of occult cancer and that it is associated with a slightly increased long-term cancer risk,” the authors wrote.

SOURCE:

The study was led by Sissel B.T. Sørensen, departments of dermatology and rheumatology, Aarhus University Hospital, Aarhus, Denmark. It was published online on June 27, 2024, in the British Journal of Dermatology.

LIMITATIONS:

The study is limited by its observational design and reliance on registry data, which may be subject to misclassification or incomplete information. In addition, the study could not assess individual patient factors such as lifestyle or genetic predispositions that may influence cancer risk, and the results may not be generalizable to other populations. Finally, the exact biologic mechanisms linking urticaria and cancer remain unclear, warranting further investigation.

DISCLOSURES:

The study did not receive any funding. The authors reported that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Bothersome urinary symptoms and incontinence at 12 months post partum are common and treatable, so screening for those symptoms as well as associated depression and anxiety is essential, write authors of a new study.

Sonia Bhandari Randhawa, MD, with the Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center in Dallas, led the study published in Urogynecology, which identified factors associated with persistent stress urinary incontinence (SUI), marked by leakage from sudden movements such as coughing or jumping; urgency UI (UUI), leakage after a sudden and intense need to urinate, even if the bladder isn’t full; and other overall bothersome urinary symptoms 1 year after delivery.
 

Associations by Subtype

Dr. Randhawa analyzed data provided by 419 patients (77% Hispanic White and 22% non-Hispanic Black). After multivariable analysis, SUI (n = 136, 32.5%) was significantly associated with greater body mass index (BMI) at the time of delivery and greater depression screening scores. Factors not associated included fetal birth weight, mode of delivery, degree of laceration, and breastfeeding status.

UUI (n = 69, 16.5%) was significantly associated with more births and higher anxiety screening scores. Women with overall urinary symptom bother also had significantly more births and higher anxiety screening scores.

“These findings support the [American College of Obstetricians and Gynecologists] recommendations for routine mental health and urinary incontinence screening in the postpartum period,” said Gena Dunivan, MD, director of the Division of Urogynecology and Pelvic Reconstructive Surgery at University of Alabama–Birmingham, who was not part of the study. “Routine screening for these issues will hopefully reduce the stigma, allowing more patients to receive the help they deserve.”
 

1 in 3 Postpartum Patients Affected by Urinary Incontinence

About one third of postpartum patients are affected by urinary incontinence, which is linked with poorer quality of life and mental health outcomes, the authors note.

Estimates of incontinence frequency post partum vary depending on the population studied, differences in subgroups, and definition of urinary incontinence. A strength of the study was its sizable population, made up almost entirely of Hispanic White and non-Hispanic Black women receiving care at a large safety-net hospital.

“This study has important clinical implications for postpartum patients,” the authors write. “Given an array of proven treatment options for both UUI and SUI, maternal health surveillance needs to include routine inquiry about UI to overcome patients’ reluctance for seeking care. Next, as elevated BMI was identified as a risk factor for persistent postpartum SUI, maintaining a healthy weight should be routinely encouraged during antenatal and postpartum clinic visits.”

Lauren Giugale, MD, director of UPMC’s Magee-Womens Hospital Postpartum Pelvic Floor Healing Clinic in Pittsburgh, Pennsylvania, says an important aspect of the study is that it measured urinary symptoms 1 year after delivery and shows that these symptoms persist. “A lot of studies look more short term,” she noted.

She also pointed to the study’s population of Black and Hispanic women, populations which “have been pretty hard to capture in urogynecology research. It’s important for us to understand these urinary symptoms are affecting those women as well as White women.”
 

Association With Anxiety

The association between postpartum depression scores and SUI is important, she says, but Dr. Randhawa’s team also “uniquely looked at anxiety scores in postpartum women. They showed an association between anxiety scores and UUI, so there’s certainly a potential impact of postpartum urinary symptoms on maternal mental health and maternal well-being.” The relationship between anxiety and depression and postpartum urinary symptoms is not well understood and warrants further research, she says.

In her role, Dr. Giugale says, she always asks about urinary symptoms, particularly in postpartum women. But she notes that some ob.gyn.s without urogynecology training may not prioritize those questions amid all the other information they need to cover.

She says she tells her residents to ask patients pointedly, “Are you having any urine leakage? Patients may not think it’s a problem that can be addressed. We do patients a disservice when we don’t ask the important questions that might potentially impact patients’ lives.”

The authors and Dr. Giugale and Dr. Dunivan report no relevant financial relationships.

Bothersome urinary symptoms and incontinence at 12 months post partum are common and treatable, so screening for those symptoms as well as associated depression and anxiety is essential, write authors of a new study.

Sonia Bhandari Randhawa, MD, with the Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center in Dallas, led the study published in Urogynecology, which identified factors associated with persistent stress urinary incontinence (SUI), marked by leakage from sudden movements such as coughing or jumping; urgency UI (UUI), leakage after a sudden and intense need to urinate, even if the bladder isn’t full; and other overall bothersome urinary symptoms 1 year after delivery.
 

Associations by Subtype

Dr. Randhawa analyzed data provided by 419 patients (77% Hispanic White and 22% non-Hispanic Black). After multivariable analysis, SUI (n = 136, 32.5%) was significantly associated with greater body mass index (BMI) at the time of delivery and greater depression screening scores. Factors not associated included fetal birth weight, mode of delivery, degree of laceration, and breastfeeding status.

UUI (n = 69, 16.5%) was significantly associated with more births and higher anxiety screening scores. Women with overall urinary symptom bother also had significantly more births and higher anxiety screening scores.

“These findings support the [American College of Obstetricians and Gynecologists] recommendations for routine mental health and urinary incontinence screening in the postpartum period,” said Gena Dunivan, MD, director of the Division of Urogynecology and Pelvic Reconstructive Surgery at University of Alabama–Birmingham, who was not part of the study. “Routine screening for these issues will hopefully reduce the stigma, allowing more patients to receive the help they deserve.”
 

1 in 3 Postpartum Patients Affected by Urinary Incontinence

About one third of postpartum patients are affected by urinary incontinence, which is linked with poorer quality of life and mental health outcomes, the authors note.

Estimates of incontinence frequency post partum vary depending on the population studied, differences in subgroups, and definition of urinary incontinence. A strength of the study was its sizable population, made up almost entirely of Hispanic White and non-Hispanic Black women receiving care at a large safety-net hospital.

“This study has important clinical implications for postpartum patients,” the authors write. “Given an array of proven treatment options for both UUI and SUI, maternal health surveillance needs to include routine inquiry about UI to overcome patients’ reluctance for seeking care. Next, as elevated BMI was identified as a risk factor for persistent postpartum SUI, maintaining a healthy weight should be routinely encouraged during antenatal and postpartum clinic visits.”

Lauren Giugale, MD, director of UPMC’s Magee-Womens Hospital Postpartum Pelvic Floor Healing Clinic in Pittsburgh, Pennsylvania, says an important aspect of the study is that it measured urinary symptoms 1 year after delivery and shows that these symptoms persist. “A lot of studies look more short term,” she noted.

She also pointed to the study’s population of Black and Hispanic women, populations which “have been pretty hard to capture in urogynecology research. It’s important for us to understand these urinary symptoms are affecting those women as well as White women.”
 

Association With Anxiety

The association between postpartum depression scores and SUI is important, she says, but Dr. Randhawa’s team also “uniquely looked at anxiety scores in postpartum women. They showed an association between anxiety scores and UUI, so there’s certainly a potential impact of postpartum urinary symptoms on maternal mental health and maternal well-being.” The relationship between anxiety and depression and postpartum urinary symptoms is not well understood and warrants further research, she says.

In her role, Dr. Giugale says, she always asks about urinary symptoms, particularly in postpartum women. But she notes that some ob.gyn.s without urogynecology training may not prioritize those questions amid all the other information they need to cover.

She says she tells her residents to ask patients pointedly, “Are you having any urine leakage? Patients may not think it’s a problem that can be addressed. We do patients a disservice when we don’t ask the important questions that might potentially impact patients’ lives.”

The authors and Dr. Giugale and Dr. Dunivan report no relevant financial relationships.

Bothersome urinary symptoms and incontinence at 12 months post partum are common and treatable, so screening for those symptoms as well as associated depression and anxiety is essential, write authors of a new study.

Sonia Bhandari Randhawa, MD, with the Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center in Dallas, led the study published in Urogynecology, which identified factors associated with persistent stress urinary incontinence (SUI), marked by leakage from sudden movements such as coughing or jumping; urgency UI (UUI), leakage after a sudden and intense need to urinate, even if the bladder isn’t full; and other overall bothersome urinary symptoms 1 year after delivery.
 

Associations by Subtype

Dr. Randhawa analyzed data provided by 419 patients (77% Hispanic White and 22% non-Hispanic Black). After multivariable analysis, SUI (n = 136, 32.5%) was significantly associated with greater body mass index (BMI) at the time of delivery and greater depression screening scores. Factors not associated included fetal birth weight, mode of delivery, degree of laceration, and breastfeeding status.

UUI (n = 69, 16.5%) was significantly associated with more births and higher anxiety screening scores. Women with overall urinary symptom bother also had significantly more births and higher anxiety screening scores.

“These findings support the [American College of Obstetricians and Gynecologists] recommendations for routine mental health and urinary incontinence screening in the postpartum period,” said Gena Dunivan, MD, director of the Division of Urogynecology and Pelvic Reconstructive Surgery at University of Alabama–Birmingham, who was not part of the study. “Routine screening for these issues will hopefully reduce the stigma, allowing more patients to receive the help they deserve.”
 

1 in 3 Postpartum Patients Affected by Urinary Incontinence

About one third of postpartum patients are affected by urinary incontinence, which is linked with poorer quality of life and mental health outcomes, the authors note.

Estimates of incontinence frequency post partum vary depending on the population studied, differences in subgroups, and definition of urinary incontinence. A strength of the study was its sizable population, made up almost entirely of Hispanic White and non-Hispanic Black women receiving care at a large safety-net hospital.

“This study has important clinical implications for postpartum patients,” the authors write. “Given an array of proven treatment options for both UUI and SUI, maternal health surveillance needs to include routine inquiry about UI to overcome patients’ reluctance for seeking care. Next, as elevated BMI was identified as a risk factor for persistent postpartum SUI, maintaining a healthy weight should be routinely encouraged during antenatal and postpartum clinic visits.”

Lauren Giugale, MD, director of UPMC’s Magee-Womens Hospital Postpartum Pelvic Floor Healing Clinic in Pittsburgh, Pennsylvania, says an important aspect of the study is that it measured urinary symptoms 1 year after delivery and shows that these symptoms persist. “A lot of studies look more short term,” she noted.

She also pointed to the study’s population of Black and Hispanic women, populations which “have been pretty hard to capture in urogynecology research. It’s important for us to understand these urinary symptoms are affecting those women as well as White women.”
 

Association With Anxiety

The association between postpartum depression scores and SUI is important, she says, but Dr. Randhawa’s team also “uniquely looked at anxiety scores in postpartum women. They showed an association between anxiety scores and UUI, so there’s certainly a potential impact of postpartum urinary symptoms on maternal mental health and maternal well-being.” The relationship between anxiety and depression and postpartum urinary symptoms is not well understood and warrants further research, she says.

In her role, Dr. Giugale says, she always asks about urinary symptoms, particularly in postpartum women. But she notes that some ob.gyn.s without urogynecology training may not prioritize those questions amid all the other information they need to cover.

She says she tells her residents to ask patients pointedly, “Are you having any urine leakage? Patients may not think it’s a problem that can be addressed. We do patients a disservice when we don’t ask the important questions that might potentially impact patients’ lives.”

The authors and Dr. Giugale and Dr. Dunivan report no relevant financial relationships.

On any given day, oncologist Mark Lewis, MD, feels like he’s seesawing between two eras of technology. 

One minute, he’s working on sequencing a tumor genome. The next, he’s sifting through pages of disorganized data from a device that has been around for decades: the fax machine. 

“If two doctors’ offices aren’t on the same electronic medical record, one of the main ways to transfer records is still by fax,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “I can go from cutting-edge innovation to relying on, at best, 1980s information technology. It just boggles my mind.”

Dr. Lewis, who has posted about his frustration with fax machines, is far from alone. Oncologists are among the many specialists across the country at the mercy of telecopiers. 

According to a 2021 report by the Office of the National Coordinator for Health Information Technology, fax and mail continue to be the most common methods for hospitals and health systems to exchange care record summaries. In 2019, nearly 8 in 10 hospitals used mail or fax to send and receive health information, the report found. 

Fax machines are still commonplace across the healthcare spectrum, said Robert Havasy, MS, senior director for informatics strategy at the Healthcare Information and Management Systems Society (HIMSS). Inertia, cost, and more pressing priorities for hospitals and medical institutions contribute to the technology sticking around, he explained. 

“Post-COVID, my guess is we’re still at over 50% of healthcare practices using fax for some reason, on a daily basis,” Mr. Havasy said in an interview. “A lot of hospitals just don’t have the time, the money, or the staff to fix that problem because there’s always something a little higher up the priority chain they need to focus on.” 

If, for instance, “you’re going to do a process redesign to reduce hospital total acquired infections, your fax machine replacement might be 10th or 12th on the list. It just never gets up to 1 or 2 because it’s ‘not that much of a problem,’ ” he added.

Or is it?

Administrators may not view fax machines as a top concern, but clinicians who deal with the machines daily see it differently. 

“What worries me is we’re taking records out of an electronic storehouse [and] converting them to a paper medium,” Dr. Lewis said. “And then we are scanning into another electronic storehouse. The more steps, the more can be lost.”

And when information is lost, patient care can be compromised. 

Slower Workflows, Care Concerns

Although there are no published data on fax machine use in oncology specifically, this outdated technology does come into play in a variety of ways along the cancer care continuum. 

Radiation oncologist David R. Penberthy, MD, said patients often seek his cancer center’s expertise for second opinions, and that requires collecting patient records from many different practices. 

“Ideally, it would come electronically, but sometimes it does come by fax,” said Dr. Penberthy, program director of radiation oncology at the University of Virginia School of Medicine in Charlottesville. “The quality of the fax is not always the best. Sometimes it’s literally a fax of a fax. You’re reading something that’s very difficult to read.” 

Orders for new tests are also typically sent and received via fax temporarily while IT teams work to integrate them into the electronic health record (EHR), Dr. Penberthy said. 

Insurers and third-party laboratories often send test results back by fax as well.

“Even if I haven’t actually sent my patient out of our institution, this crucial result may only be entered back into the record as a scanned document from a fax, which is not great because it can get lost in the other results that are reported electronically,” Dr. Lewis said. The risk here is that an ordering physician won’t see these results, which can lead to delayed or overlooked care for patients, he explained.

“To me, it’s like a blind spot,” Dr. Lewis said. “Every time we use a fax, I see it actually as an opportunity for oversight and missed opportunity to collect data.”

Dr. Penberthy said faxing can slow things down at his practice, particularly if he faxes a document to another office but receives no confirmation and has to track down what happened. 

As for cybersecurity, data that are in transit during faxing are generally considered secure and compliant with the Health Insurance Portability and Accountability Act (HIPAA), said Mr. Havasy of HIMSS. However, the Privacy Rule also requires that data remain secure while at rest, which isn’t always possible, he added. 

“That’s where faxes fall down, because generally fax machines are in public, if you will, or open areas in a hospital,” he said. “They just sit on a desk. I don’t know that the next nurse who comes up and looks through that stack was the nurse who was treating the patient.” 

Important decisions or results can also be missed when sent by fax, creating headaches for physicians and care problems for patients. 

Dr. Lewis recently experienced an insurance-related fax mishap over Memorial Day weekend. He believed his patient had access to the antinausea medication he had prescribed. When Dr. Lewis happened to check the fax machine over the weekend, he found a coverage denial for the medication from the insurer but, at that point, had no recourse to appeal because it was a long holiday weekend. 

“Had the denial been sent by an electronic means that was quicker and more readily available, it would have been possible to appeal before the holiday weekend,” he said. 

Hematologist Aaron Goodman, MD, encountered a similar problem after an insurer denied coverage of an expensive cancer drug for a patient and faxed over its reason for the denial. Dr. Goodman was not directly notified that the information arrived and didn’t learn about the denial for a week, he said. 

“There’s no ‘ding’ in my inbox if something is faxed over and scanned,” said Dr. Goodman, associate professor of medicine at UC San Diego Health. “Once I realized it was denied, I was able to rectify it, but it wasted a week of a patient not getting a drug that I felt would be beneficial for them.”

Broader Health Policy Impacts

The use of outdated technology, such as fax machines, also creates ripple effects that burden the health system, health policy experts say. 

Duplicate testing and unnecessary care are top impacts, said Julia Adler-Milstein, PhD, professor of medicine and chief of the division of clinical informatics and digital transformation at the University of California, San Francisco.

Studies show that 20%-30% of the $65 billion spent annually on lab tests is used on unnecessary duplicate tests, and another estimated $30 billion is spent each year on unnecessary duplicate medical imaging. These duplicate tests may be mitigated if hospitals adopt certified EHR technology, research shows.

Still, without EHR interoperability between institutions, new providers may be unaware that tests or past labs for patients exist, leading to repeat tests, said Dr. Adler-Milstein, who researches health IT policy with a focus on EHRs. Patients can sometimes fill in the gaps, but not always. 

“Fax machines only help close information gaps if the clinician is aware of where to seek out the information and there is someone at the other organization to locate and transmit the information in a timely manner,” Dr. Adler-Milstein said. 

Old technology and poor interoperability also greatly affect data collection for disease surveillance and monitoring, said Janet Hamilton, MPH, executive director for the Council of State and Territorial Epidemiologists. This issue was keenly demonstrated during the pandemic, Ms. Hamilton said. 

“It was tragic, quite honestly,” she said. “There was such an immense amount of data that needed to be moved quickly, and that’s when computers are at their best.”

But, she said, “we didn’t have the level of systems in place to do it well.”

Specifically, the lack of electronic case reporting in place during the pandemic — where diagnoses are documented in the record and then immediately sent to the public health system — led to reports that were delayed, not made, or had missing or incomplete information, such as patients’ race and ethnicity or other health conditions, Ms. Hamilton said. 

Incomplete or missing data hampered the ability of public health officials and researchers to understand how the virus might affect different patients.

“If you had a chronic condition like cancer, you were less likely to have a positive outcome with COVID,” Ms. Hamilton said. “But because electronic case reporting was not in place, we didn’t get some of those additional pieces of information. We didn’t have people’s underlying oncology status to then say, ‘Here are individuals with these types of characteristics, and these are the things that happen if they also have a cancer.’”