Promoting to the front line two drugs normally used in rearguard action to treat advanced renal cell carcinoma (RCC) – nivolumab (Opdivo) and cabozantinib (Cabometyx) – doubled overall response rates and progression-free survival (PFS) and significantly improved overall survival (OS), compared with first-line sunitinib (Sutent), investigators in the Checkmate 9ER trial reported.

Median PFS among patients with advanced RCC, which was the trial’s primary endpoint, was 16.6 months with nivolumab plus cabozantinib, compared with 8.3 months with sunitinib, translating into a hazard ratio of 0.51 for the combination (P < .0001). The median follow-up was 18.1 months.

Median OS had not been reached in either arm at the time of data cutoff, but the survival curves at the time of the analysis clearly favored nivolumab-cabozatinib, with an HR for death of .060 (P = .0010), said Tony K. Choueri, MD, from the Dana-Farber Cancer Institute in Boston.

“With expanding options in our patients with advanced RCC, the overall efficacy, safety, and quality-of-life benefit, as well as individual patient characteristics, are very important considerations when you select appropriate therapy,” he said in a press briefing prior to his presentation of the data in a presidential symposium at the European Society of Medical Oncology Virtual Congress 2020.

Although the nivolumab-cabozantinib combination therapy looks good, it’s late to the game, commented Dominik Berthold, MD, from the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, the invited discussant for the briefing.

“The question is, what’s the only drawback of this trial? It’s probably the fact that it’s not first in class in this situation,” he said.

Dr. Berthold noted that nivolumab-cabozantinib, if approved for the frontline setting, will join the combination of the tyrosine kinase inhibitor (TKI) axitinib (Inlyta) plus pembrolizumab (Keytruda), which, as previously reported, was associated with a nearly 50% reduction in the risk for death in the KEYNOTE-426 trial. This combination was approved by the Food and Drug Administration for the frontline setting in April 2019.

As shown in the CheckMate-214 study, the combination of the programmed cell death protein–1 (PD-1) inhibitor nivolumab with the CTLA-4 inhibitor ipilimumab (Yervoy) was associated with significantly higher objective response rates and OS rates compared with sunitinib. This combination was approved by the FDA in April 2018 as first-line therapy for patients with advanced intermediate- or poor-risk RCC.
 

CheckMate 9ER details

A total of 651 patients with previously untreated advanced or metastatic RCC that had a clear cell component in all International Metastatic RCC Database Consortium risk groups were enrolled and randomly assigned to receive either intravenous nivolumab at 240 mg every 2 weeks plus oral cabozantinib at 40 mg daily or oral sunitinib at 50 mg daily in cycles of 4 weeks on therapy/2 weeks off therapy. Patients were treated until disease progression or unacceptable toxicities occurred.

The primary PFS endpoint and the secondary OS endpoint both favored the combination, as did the objective response rate, which was 55.7% with nivolumab-cabozantinib versus 27.1% with sunitinib (P < .0001).

Complete responses were seen in 8% of patients who received the combination versus 4.6% with the patients who received sunitinib. Partial responses were seen in 47.7% and 22.6%, respectively.

Patients generally tolerated the combination. The incidence of the most common high-grade treatment-emergent adverse events and other adverse events of any grade was similar to that seen with sunitinib, Dr. Choueri said.

The rates of treatment-related events that led to discontinuation was 3.1% among patients who received the combination, 5.6% among patients who received the nivolumab component only, and 6.6% among patients who received cabozantinib only. It was 8.8% among patients who received sunitinib. More than 50% of patients in the combination arm needed a dose reduction of nivolumab-cabozantinib because of adverse events, however.

“Overall, it seems that the combination has a somewhat manageable safety profile in patients with advanced RCC,” Dr. Choueri said.

Patient-reported quality of life, as measured by the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy–Kidney Symptom Index 19 total score, was an exploratory endpoint. It was maintained over time with the combination but deteriorated over time with sunitinib, with statistically significant differences between the study arms at most time points to 91 weeks, he reported.
 

Making choices

Dr. Berthold acknowledged the benefit that having an additional therapy offers clinicians and patients.

“What we still need to learn here is, ‘Are there any patient populations who may benefit more on this combination compared with other combinations?’ ” he said. “Cabozantinib is quite a unique TKI which may target better bone metastases, for example, so I think there are things we need to learn from further data and longer follow-up.”

Camillo Porta, MD, from the University of Bari (Italy), the invited discussant for the presidential symposium, urged caution in comparing the three regimens, owing to differences in the drug used, study endpoints, baseline patient characteristics, and the distribution of patients among different prognostic groups.

When it comes to deciding between frontline regimens, “the only possible, though highly empiric, driver of our therapeutical choice should be the biological aggressiveness of the tumor,” he said.

For patients with highly aggressive disease, the use of an immune checkpoint inhibitor plus a vascular endothelial growth factor receptor (VEGFR)–directed TKI may help control disease long enough to give the checkpoint inhibitor time to work.

“Otherwise, one could head for the long-term benefit of the immune combo as well as for complete responses, trying to spare [patients] the additional toxicities deriving from the continuous use of the VEGFR TKI,” he added.

Dr. Porta noted that when considering the trade-off between efficacy and safety in the first-line setting, many patients are willing to accept more toxicities in exchange for clinical benefit.

The study was sponsored by Bristol-Myers Squibb. Dr. Choueri disclosed consultancy fees, advisory board activity, manuscript preparation, travel/lodging, honoraria, and grants for clinical trials from BMS and others. Dr. Berthold disclosed an advisory role for Ipsen, BMS, Merck, and Pfizer. Dr. Porta disclosed advisory/consulting activities and speakers bureau participation for BMS and others.

This article first appeared on Medscape.com.

Promoting to the front line two drugs normally used in rearguard action to treat advanced renal cell carcinoma (RCC) – nivolumab (Opdivo) and cabozantinib (Cabometyx) – doubled overall response rates and progression-free survival (PFS) and significantly improved overall survival (OS), compared with first-line sunitinib (Sutent), investigators in the Checkmate 9ER trial reported.

Median PFS among patients with advanced RCC, which was the trial’s primary endpoint, was 16.6 months with nivolumab plus cabozantinib, compared with 8.3 months with sunitinib, translating into a hazard ratio of 0.51 for the combination (P < .0001). The median follow-up was 18.1 months.

Median OS had not been reached in either arm at the time of data cutoff, but the survival curves at the time of the analysis clearly favored nivolumab-cabozatinib, with an HR for death of .060 (P = .0010), said Tony K. Choueri, MD, from the Dana-Farber Cancer Institute in Boston.

“With expanding options in our patients with advanced RCC, the overall efficacy, safety, and quality-of-life benefit, as well as individual patient characteristics, are very important considerations when you select appropriate therapy,” he said in a press briefing prior to his presentation of the data in a presidential symposium at the European Society of Medical Oncology Virtual Congress 2020.

Although the nivolumab-cabozantinib combination therapy looks good, it’s late to the game, commented Dominik Berthold, MD, from the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, the invited discussant for the briefing.

“The question is, what’s the only drawback of this trial? It’s probably the fact that it’s not first in class in this situation,” he said.

Dr. Berthold noted that nivolumab-cabozantinib, if approved for the frontline setting, will join the combination of the tyrosine kinase inhibitor (TKI) axitinib (Inlyta) plus pembrolizumab (Keytruda), which, as previously reported, was associated with a nearly 50% reduction in the risk for death in the KEYNOTE-426 trial. This combination was approved by the Food and Drug Administration for the frontline setting in April 2019.

As shown in the CheckMate-214 study, the combination of the programmed cell death protein–1 (PD-1) inhibitor nivolumab with the CTLA-4 inhibitor ipilimumab (Yervoy) was associated with significantly higher objective response rates and OS rates compared with sunitinib. This combination was approved by the FDA in April 2018 as first-line therapy for patients with advanced intermediate- or poor-risk RCC.
 

CheckMate 9ER details

A total of 651 patients with previously untreated advanced or metastatic RCC that had a clear cell component in all International Metastatic RCC Database Consortium risk groups were enrolled and randomly assigned to receive either intravenous nivolumab at 240 mg every 2 weeks plus oral cabozantinib at 40 mg daily or oral sunitinib at 50 mg daily in cycles of 4 weeks on therapy/2 weeks off therapy. Patients were treated until disease progression or unacceptable toxicities occurred.

The primary PFS endpoint and the secondary OS endpoint both favored the combination, as did the objective response rate, which was 55.7% with nivolumab-cabozantinib versus 27.1% with sunitinib (P < .0001).

Complete responses were seen in 8% of patients who received the combination versus 4.6% with the patients who received sunitinib. Partial responses were seen in 47.7% and 22.6%, respectively.

Patients generally tolerated the combination. The incidence of the most common high-grade treatment-emergent adverse events and other adverse events of any grade was similar to that seen with sunitinib, Dr. Choueri said.

The rates of treatment-related events that led to discontinuation was 3.1% among patients who received the combination, 5.6% among patients who received the nivolumab component only, and 6.6% among patients who received cabozantinib only. It was 8.8% among patients who received sunitinib. More than 50% of patients in the combination arm needed a dose reduction of nivolumab-cabozantinib because of adverse events, however.

“Overall, it seems that the combination has a somewhat manageable safety profile in patients with advanced RCC,” Dr. Choueri said.

Patient-reported quality of life, as measured by the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy–Kidney Symptom Index 19 total score, was an exploratory endpoint. It was maintained over time with the combination but deteriorated over time with sunitinib, with statistically significant differences between the study arms at most time points to 91 weeks, he reported.
 

Making choices

Dr. Berthold acknowledged the benefit that having an additional therapy offers clinicians and patients.

“What we still need to learn here is, ‘Are there any patient populations who may benefit more on this combination compared with other combinations?’ ” he said. “Cabozantinib is quite a unique TKI which may target better bone metastases, for example, so I think there are things we need to learn from further data and longer follow-up.”

Camillo Porta, MD, from the University of Bari (Italy), the invited discussant for the presidential symposium, urged caution in comparing the three regimens, owing to differences in the drug used, study endpoints, baseline patient characteristics, and the distribution of patients among different prognostic groups.

When it comes to deciding between frontline regimens, “the only possible, though highly empiric, driver of our therapeutical choice should be the biological aggressiveness of the tumor,” he said.

For patients with highly aggressive disease, the use of an immune checkpoint inhibitor plus a vascular endothelial growth factor receptor (VEGFR)–directed TKI may help control disease long enough to give the checkpoint inhibitor time to work.

“Otherwise, one could head for the long-term benefit of the immune combo as well as for complete responses, trying to spare [patients] the additional toxicities deriving from the continuous use of the VEGFR TKI,” he added.

Dr. Porta noted that when considering the trade-off between efficacy and safety in the first-line setting, many patients are willing to accept more toxicities in exchange for clinical benefit.

The study was sponsored by Bristol-Myers Squibb. Dr. Choueri disclosed consultancy fees, advisory board activity, manuscript preparation, travel/lodging, honoraria, and grants for clinical trials from BMS and others. Dr. Berthold disclosed an advisory role for Ipsen, BMS, Merck, and Pfizer. Dr. Porta disclosed advisory/consulting activities and speakers bureau participation for BMS and others.

This article first appeared on Medscape.com.

Promoting to the front line two drugs normally used in rearguard action to treat advanced renal cell carcinoma (RCC) – nivolumab (Opdivo) and cabozantinib (Cabometyx) – doubled overall response rates and progression-free survival (PFS) and significantly improved overall survival (OS), compared with first-line sunitinib (Sutent), investigators in the Checkmate 9ER trial reported.

Median PFS among patients with advanced RCC, which was the trial’s primary endpoint, was 16.6 months with nivolumab plus cabozantinib, compared with 8.3 months with sunitinib, translating into a hazard ratio of 0.51 for the combination (P < .0001). The median follow-up was 18.1 months.

Median OS had not been reached in either arm at the time of data cutoff, but the survival curves at the time of the analysis clearly favored nivolumab-cabozatinib, with an HR for death of .060 (P = .0010), said Tony K. Choueri, MD, from the Dana-Farber Cancer Institute in Boston.

“With expanding options in our patients with advanced RCC, the overall efficacy, safety, and quality-of-life benefit, as well as individual patient characteristics, are very important considerations when you select appropriate therapy,” he said in a press briefing prior to his presentation of the data in a presidential symposium at the European Society of Medical Oncology Virtual Congress 2020.

Although the nivolumab-cabozantinib combination therapy looks good, it’s late to the game, commented Dominik Berthold, MD, from the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, the invited discussant for the briefing.

“The question is, what’s the only drawback of this trial? It’s probably the fact that it’s not first in class in this situation,” he said.

Dr. Berthold noted that nivolumab-cabozantinib, if approved for the frontline setting, will join the combination of the tyrosine kinase inhibitor (TKI) axitinib (Inlyta) plus pembrolizumab (Keytruda), which, as previously reported, was associated with a nearly 50% reduction in the risk for death in the KEYNOTE-426 trial. This combination was approved by the Food and Drug Administration for the frontline setting in April 2019.

As shown in the CheckMate-214 study, the combination of the programmed cell death protein–1 (PD-1) inhibitor nivolumab with the CTLA-4 inhibitor ipilimumab (Yervoy) was associated with significantly higher objective response rates and OS rates compared with sunitinib. This combination was approved by the FDA in April 2018 as first-line therapy for patients with advanced intermediate- or poor-risk RCC.
 

CheckMate 9ER details

A total of 651 patients with previously untreated advanced or metastatic RCC that had a clear cell component in all International Metastatic RCC Database Consortium risk groups were enrolled and randomly assigned to receive either intravenous nivolumab at 240 mg every 2 weeks plus oral cabozantinib at 40 mg daily or oral sunitinib at 50 mg daily in cycles of 4 weeks on therapy/2 weeks off therapy. Patients were treated until disease progression or unacceptable toxicities occurred.

The primary PFS endpoint and the secondary OS endpoint both favored the combination, as did the objective response rate, which was 55.7% with nivolumab-cabozantinib versus 27.1% with sunitinib (P < .0001).

Complete responses were seen in 8% of patients who received the combination versus 4.6% with the patients who received sunitinib. Partial responses were seen in 47.7% and 22.6%, respectively.

Patients generally tolerated the combination. The incidence of the most common high-grade treatment-emergent adverse events and other adverse events of any grade was similar to that seen with sunitinib, Dr. Choueri said.

The rates of treatment-related events that led to discontinuation was 3.1% among patients who received the combination, 5.6% among patients who received the nivolumab component only, and 6.6% among patients who received cabozantinib only. It was 8.8% among patients who received sunitinib. More than 50% of patients in the combination arm needed a dose reduction of nivolumab-cabozantinib because of adverse events, however.

“Overall, it seems that the combination has a somewhat manageable safety profile in patients with advanced RCC,” Dr. Choueri said.

Patient-reported quality of life, as measured by the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy–Kidney Symptom Index 19 total score, was an exploratory endpoint. It was maintained over time with the combination but deteriorated over time with sunitinib, with statistically significant differences between the study arms at most time points to 91 weeks, he reported.
 

Making choices

Dr. Berthold acknowledged the benefit that having an additional therapy offers clinicians and patients.

“What we still need to learn here is, ‘Are there any patient populations who may benefit more on this combination compared with other combinations?’ ” he said. “Cabozantinib is quite a unique TKI which may target better bone metastases, for example, so I think there are things we need to learn from further data and longer follow-up.”

Camillo Porta, MD, from the University of Bari (Italy), the invited discussant for the presidential symposium, urged caution in comparing the three regimens, owing to differences in the drug used, study endpoints, baseline patient characteristics, and the distribution of patients among different prognostic groups.

When it comes to deciding between frontline regimens, “the only possible, though highly empiric, driver of our therapeutical choice should be the biological aggressiveness of the tumor,” he said.

For patients with highly aggressive disease, the use of an immune checkpoint inhibitor plus a vascular endothelial growth factor receptor (VEGFR)–directed TKI may help control disease long enough to give the checkpoint inhibitor time to work.

“Otherwise, one could head for the long-term benefit of the immune combo as well as for complete responses, trying to spare [patients] the additional toxicities deriving from the continuous use of the VEGFR TKI,” he added.

Dr. Porta noted that when considering the trade-off between efficacy and safety in the first-line setting, many patients are willing to accept more toxicities in exchange for clinical benefit.

The study was sponsored by Bristol-Myers Squibb. Dr. Choueri disclosed consultancy fees, advisory board activity, manuscript preparation, travel/lodging, honoraria, and grants for clinical trials from BMS and others. Dr. Berthold disclosed an advisory role for Ipsen, BMS, Merck, and Pfizer. Dr. Porta disclosed advisory/consulting activities and speakers bureau participation for BMS and others.

This article first appeared on Medscape.com.

First-line lorlatinib significantly prolonged progression-free survival (PFS) when compared with crizotinib in advanced ALK-positive non–small cell lung cancer (NSCLC), according to an interim analysis of the phase 3 CROWN trial.

Lorlatinib also produced a higher overall and intracranial response rate, prolonging progression to CNS disease.

These findings “support the use of lorlatinib as a highly effective first-line therapy for patients with advanced ALK-positive NSCLC,” said Benjamin Solomon, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne.

“The CROWN study clearly establishes lorlatinib as another option” among other first-line ALK inhibitors, Dr. Solomon said when presenting the findings at the European Society for Medical Oncology Virtual Congress 2020.

“We now have multiple options for first-line treatment of patients with ALK-positive lung cancer,” noted study discussant Christine Lovly, MD, PhD, a medical oncologist and associate professor at Vanderbilt University Medical Center in Nashville, Tenn.

The question now, she said, is how to choose among these options. The drugs have all bested crizotinib in trials but haven’t gone head to head against one another.
 

Lorlatinib and CROWN

Lorlatinib is currently approved in the United States to treat ALK-positive metastatic NSCLC that has progressed on crizotinib and at least one other ALK inhibitor. Lorlatinib was granted accelerated approval for this indication based on response rate and duration.

The CROWN study was intended to support the conversion to full approval, according to Pfizer, which is developing both lorlatinib and crizotinib. Pfizer also plans to use the results of CROWN to seek a first-line indication for lorlatinib in NSCLC.

CROWN enrolled 296 patients with stage IIIB/IV ALK-positive NSCLC who had received no prior systemic treatment. Patients with asymptomatic treated or untreated CNS metastases were eligible.

There were 149 patients randomized to lorlatinib at 100 mg daily and 147 randomized to crizotinib at 250 mg twice daily. Five patients in the crizotinib arm were included in the analysis but were not treated, Dr. Solomon said.

The median age was 61 years in the lorlatinib arm and 56 years in the crizotinib arm. Nearly all patients were White (48% in the lorlatinib arm and 49% in the crizotinib arm) or Asian (44% in both arms). A majority of patients were women (56% in the lorlatinib arm and 62% in the crizotinib arm), and more than half said they never smoked (54% in the lorlatinib arm and 64% in the crizotinib arm).
 

Response and PFS

According to blinded independent central review, the objective response rate was 76% with lorlatinib (113/149) and 58% with crizotinib (85/147). There were four complete responses with lorlatinib and none with crizotinib.

Among patients who had measurable or nonmeasurable brain metastases at baseline, the intracranial ORR was 66% with lorlatinib (25/38) and 20% (8/40) with crizotinib. In patients with only measurable brain metastases at baseline, the intracranial ORR was 82% with lorlatinib (14/17) and 23% with crizotinib (3/13).

The 12-month PFS rate was 78% in the lorlatinib arm and 39% in the crizotinib arm. The median PFS was 9.3 months in the crizotinib arm but was not reached in the lorlatinib arm, which “corresponded to a 72% reduction in the risk of death or progression [hazard ratio, 0.21; P < .001],” Dr. Solomon said.

“[T]he PFS for alectinib in the first line is approximately 3 years,” Dr. Lovly noted. “We anxiously await additional data for lorlatinib to see how long the PFS will be.”

The median time to intracranial progression was 16.6 months in the crizotinib arm but was not reached in the lorlatinib arm (HR, 0.07; P < .001).

“These data indicate the ability of lorlatinib not only to delay the progression of existing brain metastases, but also to prevent the development of new brain metastases,” Dr. Solomon said.

Dr. Lovly noted that the efficacy of lorlatinib in the brain is “quite compelling,” but other ALK inhibitors have demonstrated similar results.

As for overall survival, the data are still immature. The median overall survival was not reached with lorlatinib or crizotinib (HR, 0.72).
 

Toxicity

Dr. Solomon noted that lorlatinib “does have a different toxicity profile, compared to other ALK inhibitors.” Specifically, lorlatinib is associated with hypercholesterolemia and hypertriglyceridemia, which have not been seen with other ALK inhibitors.

Lorlatinib is also associated with neurocognitive problems, including inattention, memory impairment, and mild confusion. Mood effects include emotional lability – “someone watching a movie might burst into tears when they wouldn’t have otherwise,” Dr. Solomon said – as well as anxiety and depression.

“So it’s important to tell not just the patient but their family about these things so that they identify when [the events] happen,” Dr. Solomon said. “That’s key because [the events are] completely reversible when you stop the drug. With dose interruption, those effects will resolve.”

Other adverse events that were more common with lorlatinib (a 10% or greater difference in frequency from crizotinib) included edema, weight gain, and peripheral neuropathy. Diarrhea, nausea, fatigue, vision disorders, constipation, and increased liver enzymes were more common with crizotinib. Grade 3-4 adverse events led to discontinuation in fewer than 10% of patients in each arm.

The study was funded by Pfizer, and the investigators included employees. Dr. Solomon is an adviser for Pfizer and other companies, and Dr. Lovly’s industry ties included being both an advisor and speaker for Pfizer.

[email protected]

SOURCE: Solomon B et al. ESMO 2020, Abstract LBA2.

First-line lorlatinib significantly prolonged progression-free survival (PFS) when compared with crizotinib in advanced ALK-positive non–small cell lung cancer (NSCLC), according to an interim analysis of the phase 3 CROWN trial.

Lorlatinib also produced a higher overall and intracranial response rate, prolonging progression to CNS disease.

These findings “support the use of lorlatinib as a highly effective first-line therapy for patients with advanced ALK-positive NSCLC,” said Benjamin Solomon, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne.

“The CROWN study clearly establishes lorlatinib as another option” among other first-line ALK inhibitors, Dr. Solomon said when presenting the findings at the European Society for Medical Oncology Virtual Congress 2020.

“We now have multiple options for first-line treatment of patients with ALK-positive lung cancer,” noted study discussant Christine Lovly, MD, PhD, a medical oncologist and associate professor at Vanderbilt University Medical Center in Nashville, Tenn.

The question now, she said, is how to choose among these options. The drugs have all bested crizotinib in trials but haven’t gone head to head against one another.
 

Lorlatinib and CROWN

Lorlatinib is currently approved in the United States to treat ALK-positive metastatic NSCLC that has progressed on crizotinib and at least one other ALK inhibitor. Lorlatinib was granted accelerated approval for this indication based on response rate and duration.

The CROWN study was intended to support the conversion to full approval, according to Pfizer, which is developing both lorlatinib and crizotinib. Pfizer also plans to use the results of CROWN to seek a first-line indication for lorlatinib in NSCLC.

CROWN enrolled 296 patients with stage IIIB/IV ALK-positive NSCLC who had received no prior systemic treatment. Patients with asymptomatic treated or untreated CNS metastases were eligible.

There were 149 patients randomized to lorlatinib at 100 mg daily and 147 randomized to crizotinib at 250 mg twice daily. Five patients in the crizotinib arm were included in the analysis but were not treated, Dr. Solomon said.

The median age was 61 years in the lorlatinib arm and 56 years in the crizotinib arm. Nearly all patients were White (48% in the lorlatinib arm and 49% in the crizotinib arm) or Asian (44% in both arms). A majority of patients were women (56% in the lorlatinib arm and 62% in the crizotinib arm), and more than half said they never smoked (54% in the lorlatinib arm and 64% in the crizotinib arm).
 

Response and PFS

According to blinded independent central review, the objective response rate was 76% with lorlatinib (113/149) and 58% with crizotinib (85/147). There were four complete responses with lorlatinib and none with crizotinib.

Among patients who had measurable or nonmeasurable brain metastases at baseline, the intracranial ORR was 66% with lorlatinib (25/38) and 20% (8/40) with crizotinib. In patients with only measurable brain metastases at baseline, the intracranial ORR was 82% with lorlatinib (14/17) and 23% with crizotinib (3/13).

The 12-month PFS rate was 78% in the lorlatinib arm and 39% in the crizotinib arm. The median PFS was 9.3 months in the crizotinib arm but was not reached in the lorlatinib arm, which “corresponded to a 72% reduction in the risk of death or progression [hazard ratio, 0.21; P < .001],” Dr. Solomon said.

“[T]he PFS for alectinib in the first line is approximately 3 years,” Dr. Lovly noted. “We anxiously await additional data for lorlatinib to see how long the PFS will be.”

The median time to intracranial progression was 16.6 months in the crizotinib arm but was not reached in the lorlatinib arm (HR, 0.07; P < .001).

“These data indicate the ability of lorlatinib not only to delay the progression of existing brain metastases, but also to prevent the development of new brain metastases,” Dr. Solomon said.

Dr. Lovly noted that the efficacy of lorlatinib in the brain is “quite compelling,” but other ALK inhibitors have demonstrated similar results.

As for overall survival, the data are still immature. The median overall survival was not reached with lorlatinib or crizotinib (HR, 0.72).
 

Toxicity

Dr. Solomon noted that lorlatinib “does have a different toxicity profile, compared to other ALK inhibitors.” Specifically, lorlatinib is associated with hypercholesterolemia and hypertriglyceridemia, which have not been seen with other ALK inhibitors.

Lorlatinib is also associated with neurocognitive problems, including inattention, memory impairment, and mild confusion. Mood effects include emotional lability – “someone watching a movie might burst into tears when they wouldn’t have otherwise,” Dr. Solomon said – as well as anxiety and depression.

“So it’s important to tell not just the patient but their family about these things so that they identify when [the events] happen,” Dr. Solomon said. “That’s key because [the events are] completely reversible when you stop the drug. With dose interruption, those effects will resolve.”

Other adverse events that were more common with lorlatinib (a 10% or greater difference in frequency from crizotinib) included edema, weight gain, and peripheral neuropathy. Diarrhea, nausea, fatigue, vision disorders, constipation, and increased liver enzymes were more common with crizotinib. Grade 3-4 adverse events led to discontinuation in fewer than 10% of patients in each arm.

The study was funded by Pfizer, and the investigators included employees. Dr. Solomon is an adviser for Pfizer and other companies, and Dr. Lovly’s industry ties included being both an advisor and speaker for Pfizer.

[email protected]

SOURCE: Solomon B et al. ESMO 2020, Abstract LBA2.

First-line lorlatinib significantly prolonged progression-free survival (PFS) when compared with crizotinib in advanced ALK-positive non–small cell lung cancer (NSCLC), according to an interim analysis of the phase 3 CROWN trial.

Lorlatinib also produced a higher overall and intracranial response rate, prolonging progression to CNS disease.

These findings “support the use of lorlatinib as a highly effective first-line therapy for patients with advanced ALK-positive NSCLC,” said Benjamin Solomon, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne.

“The CROWN study clearly establishes lorlatinib as another option” among other first-line ALK inhibitors, Dr. Solomon said when presenting the findings at the European Society for Medical Oncology Virtual Congress 2020.

“We now have multiple options for first-line treatment of patients with ALK-positive lung cancer,” noted study discussant Christine Lovly, MD, PhD, a medical oncologist and associate professor at Vanderbilt University Medical Center in Nashville, Tenn.

The question now, she said, is how to choose among these options. The drugs have all bested crizotinib in trials but haven’t gone head to head against one another.
 

Lorlatinib and CROWN

Lorlatinib is currently approved in the United States to treat ALK-positive metastatic NSCLC that has progressed on crizotinib and at least one other ALK inhibitor. Lorlatinib was granted accelerated approval for this indication based on response rate and duration.

The CROWN study was intended to support the conversion to full approval, according to Pfizer, which is developing both lorlatinib and crizotinib. Pfizer also plans to use the results of CROWN to seek a first-line indication for lorlatinib in NSCLC.

CROWN enrolled 296 patients with stage IIIB/IV ALK-positive NSCLC who had received no prior systemic treatment. Patients with asymptomatic treated or untreated CNS metastases were eligible.

There were 149 patients randomized to lorlatinib at 100 mg daily and 147 randomized to crizotinib at 250 mg twice daily. Five patients in the crizotinib arm were included in the analysis but were not treated, Dr. Solomon said.

The median age was 61 years in the lorlatinib arm and 56 years in the crizotinib arm. Nearly all patients were White (48% in the lorlatinib arm and 49% in the crizotinib arm) or Asian (44% in both arms). A majority of patients were women (56% in the lorlatinib arm and 62% in the crizotinib arm), and more than half said they never smoked (54% in the lorlatinib arm and 64% in the crizotinib arm).
 

Response and PFS

According to blinded independent central review, the objective response rate was 76% with lorlatinib (113/149) and 58% with crizotinib (85/147). There were four complete responses with lorlatinib and none with crizotinib.

Among patients who had measurable or nonmeasurable brain metastases at baseline, the intracranial ORR was 66% with lorlatinib (25/38) and 20% (8/40) with crizotinib. In patients with only measurable brain metastases at baseline, the intracranial ORR was 82% with lorlatinib (14/17) and 23% with crizotinib (3/13).

The 12-month PFS rate was 78% in the lorlatinib arm and 39% in the crizotinib arm. The median PFS was 9.3 months in the crizotinib arm but was not reached in the lorlatinib arm, which “corresponded to a 72% reduction in the risk of death or progression [hazard ratio, 0.21; P < .001],” Dr. Solomon said.

“[T]he PFS for alectinib in the first line is approximately 3 years,” Dr. Lovly noted. “We anxiously await additional data for lorlatinib to see how long the PFS will be.”

The median time to intracranial progression was 16.6 months in the crizotinib arm but was not reached in the lorlatinib arm (HR, 0.07; P < .001).

“These data indicate the ability of lorlatinib not only to delay the progression of existing brain metastases, but also to prevent the development of new brain metastases,” Dr. Solomon said.

Dr. Lovly noted that the efficacy of lorlatinib in the brain is “quite compelling,” but other ALK inhibitors have demonstrated similar results.

As for overall survival, the data are still immature. The median overall survival was not reached with lorlatinib or crizotinib (HR, 0.72).
 

Toxicity

Dr. Solomon noted that lorlatinib “does have a different toxicity profile, compared to other ALK inhibitors.” Specifically, lorlatinib is associated with hypercholesterolemia and hypertriglyceridemia, which have not been seen with other ALK inhibitors.

Lorlatinib is also associated with neurocognitive problems, including inattention, memory impairment, and mild confusion. Mood effects include emotional lability – “someone watching a movie might burst into tears when they wouldn’t have otherwise,” Dr. Solomon said – as well as anxiety and depression.

“So it’s important to tell not just the patient but their family about these things so that they identify when [the events] happen,” Dr. Solomon said. “That’s key because [the events are] completely reversible when you stop the drug. With dose interruption, those effects will resolve.”

Other adverse events that were more common with lorlatinib (a 10% or greater difference in frequency from crizotinib) included edema, weight gain, and peripheral neuropathy. Diarrhea, nausea, fatigue, vision disorders, constipation, and increased liver enzymes were more common with crizotinib. Grade 3-4 adverse events led to discontinuation in fewer than 10% of patients in each arm.

The study was funded by Pfizer, and the investigators included employees. Dr. Solomon is an adviser for Pfizer and other companies, and Dr. Lovly’s industry ties included being both an advisor and speaker for Pfizer.

[email protected]

SOURCE: Solomon B et al. ESMO 2020, Abstract LBA2.

On March 3 of this year, Bryant Cameron Webb, MD, JD, won two-thirds of the vote in Virginia’s Democratic primary race. In November, he’ll compete against Republican Bob Good to represent the state’s 5th Congressional District. If he succeeds, he will become the first Black physician ever elected to a seat in Congress.

Courtesy Dr. Bryant Cameron Webb

The political and social unrest across the United States in recent months has resulted in millions of people becoming more proactive: from sports arenas to the halls of Congress, the rally cry of Black Lives Matter has echoed like never before after the killing of George Floyd and Breonna Taylor at the hands of law enforcement. Dr. Webb, a practicing internist and professor at the University of Virginia, Charlottesville, is among many physicians joining the cause. If elected, he hopes to bring a unique perspective to Washington and advocate for racial equity to help combat systemic racist policies that result in health disparities.

“For me as a professor at UVA in both public health sciences and in medicine, I have a lot to bring to this moment,” he commented, “real expertise on issues that are critical to the nation. Beyond my passion for health and wellness, I have a passion for justice.”

Dr. Webb also believes that serving in Congress is a way to help his patients. “I balance the work of direct patient care and patient advocacy in different spaces,” said the Spotsylvania County native. “Working in Congress is patient advocacy to me. It’s where I can be at my highest use to the people I take care of. It is different from direct patient care. I think this [unique] background that I have is needed in Congress.”

Dr. Webb has never held an elected office before, and he’s looking to get elected in a district that voted for President Trump in the past election. He knows challenges lie ahead.
 

A calling

The field of medicine called for Dr. Webb at an early age. He credits his family doctor, a Black man, for inspiring him. “With six kids in our family, we saw the doctor frequently. Dr. Yarboro was a young Black man just a few years out of residency. My mom had supreme confidence in him, and he made us feel at ease. So I wanted to be a doctor ever since I was 5 or 6 years old.”

Dr. Webb earned a bachelor’s degree from the University of Virginia in 2005. He entered medical school at Wake Forest University, Winston-Salem, N.C., the following year. Following his third year of medical training, he heeded another calling: He took time off to attend law school. He enrolled in Loyola University of Chicago School of Law and earned his juris doctorate in 2012.

The move may seem an unexpected turn. But Dr. Webb feels his law degree enhances his work. “I think that it’s because I’m so steeped in the legal resources that folks need to navigate. I think I am able to provide better care. ... It’s a complement and helpful to me professionally, whether it’s fighting with an insurance company or with a prescription drug company.”

After law school, Dr. Webb finished his medical training at Wake Forest and moved north, where he completed an internal medicine residency at New York–Presbyterian Hospital. Then came yet another twist in Dr. Webb’s unconventional career path: in 2016, he was selected by President Obama as a White House fellow. He spent the next 2 years in Washington, where he worked on Mr. Obama’s My Brother’s Keeper Task Force, an initiative that addresses opportunity gaps faced by boys and young men of color.

Adeze Enekwechi, MD, president of Impaq and associate professor at the George Washington University, Washington, worked with Dr. Webb at the White House. “This is the place where he will have the most impact. We’ve been talking and writing about health equity ever since our time [there]. Not everybody can speak that language. Being an African American male physician and an attorney can really help drive change by being the right person at the table.”
 

Why here? Why now?

Dr. Webb sees patients 2-3 days a week on alternating weeks and knows well the concerns of people who struggle with health. Now he’s ready to have those conversations on a larger platform. “As a Black physician, it’s about bringing that healer mindset to these problems. It’s not about just going there to brow beat people or add to that divisive nature in Congress. You acknowledge that the problems exist, and then bridge,” he said, hoping that bridging party divides can be a catalyst for healing.

Carla Boutin-Foster, MD, associate dean, office of diversity education and research at the State University of New York, Brooklyn, has mentored Dr. Webb since 2013. With his credentials, confidence, and persistence, she believes, he will be a great representative of the medical community in D.C. “You need someone who respects the Constitution. When policy needs to be developed, you need a healer, someone who understands the science of vaccines. This is something Cam has been groomed for. It’s something he has been living and practicing for years.”

The killing of George Floyd and the uprising that ensued has opened the dialogue about racial inequality in America. Health care is not immune to racial bias, and the effects are palatable. One survey conducted by the Larry A. Green Center, in collaboration with the Primary Care Collaborative and 3rd Conversation, found that more than 40% of clinicians say Mr. Floyd’s demise has become a topic of concern among patients of all demographics.

When it comes to racism, Dr. Webb understands that he plays a critical role in moving America forward. “We have so many voices that are powerful and important in the highest level of legislation. We have to use those voices to root out the injustices in our society, like in the Breonna Taylor case. We have to do so because that is how you achieve the American dream,” he said.

The social determinants of health – or “ZIP-code risk” – has been proven to influence health outcomes, yet few physicians screen for them during patient visits. For Dr. Webb, discussing things like housing security and interpersonal violence are critical to providing care.

One of Dr. Webb’s biggest supporters is his wife of 11 years, Leigh Ann Webb, MD, MBA, an emergency medicine physician and assistant professor of emergency medicine at UVA. “He is an effective leader and a consensus builder,” she said of her husband, with whom she has two children. “There has always been something very unique and special about him and the way he engages the world. We need more thoughtful, intelligent people like him to help our country move forward.”

In addition to being the director of health policy and equity at UVA this fall, Dr. Webb plans to teach a course at UVA centered around the social determinants of health called Place Matters. “The focus is on understanding how education and housing and food insecurity all come together to cause illness,” he said. “Health doesn’t happen in hospitals and clinics. It happens in the community.”

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

On March 3 of this year, Bryant Cameron Webb, MD, JD, won two-thirds of the vote in Virginia’s Democratic primary race. In November, he’ll compete against Republican Bob Good to represent the state’s 5th Congressional District. If he succeeds, he will become the first Black physician ever elected to a seat in Congress.

Courtesy Dr. Bryant Cameron Webb

The political and social unrest across the United States in recent months has resulted in millions of people becoming more proactive: from sports arenas to the halls of Congress, the rally cry of Black Lives Matter has echoed like never before after the killing of George Floyd and Breonna Taylor at the hands of law enforcement. Dr. Webb, a practicing internist and professor at the University of Virginia, Charlottesville, is among many physicians joining the cause. If elected, he hopes to bring a unique perspective to Washington and advocate for racial equity to help combat systemic racist policies that result in health disparities.

“For me as a professor at UVA in both public health sciences and in medicine, I have a lot to bring to this moment,” he commented, “real expertise on issues that are critical to the nation. Beyond my passion for health and wellness, I have a passion for justice.”

Dr. Webb also believes that serving in Congress is a way to help his patients. “I balance the work of direct patient care and patient advocacy in different spaces,” said the Spotsylvania County native. “Working in Congress is patient advocacy to me. It’s where I can be at my highest use to the people I take care of. It is different from direct patient care. I think this [unique] background that I have is needed in Congress.”

Dr. Webb has never held an elected office before, and he’s looking to get elected in a district that voted for President Trump in the past election. He knows challenges lie ahead.
 

A calling

The field of medicine called for Dr. Webb at an early age. He credits his family doctor, a Black man, for inspiring him. “With six kids in our family, we saw the doctor frequently. Dr. Yarboro was a young Black man just a few years out of residency. My mom had supreme confidence in him, and he made us feel at ease. So I wanted to be a doctor ever since I was 5 or 6 years old.”

Dr. Webb earned a bachelor’s degree from the University of Virginia in 2005. He entered medical school at Wake Forest University, Winston-Salem, N.C., the following year. Following his third year of medical training, he heeded another calling: He took time off to attend law school. He enrolled in Loyola University of Chicago School of Law and earned his juris doctorate in 2012.

The move may seem an unexpected turn. But Dr. Webb feels his law degree enhances his work. “I think that it’s because I’m so steeped in the legal resources that folks need to navigate. I think I am able to provide better care. ... It’s a complement and helpful to me professionally, whether it’s fighting with an insurance company or with a prescription drug company.”

After law school, Dr. Webb finished his medical training at Wake Forest and moved north, where he completed an internal medicine residency at New York–Presbyterian Hospital. Then came yet another twist in Dr. Webb’s unconventional career path: in 2016, he was selected by President Obama as a White House fellow. He spent the next 2 years in Washington, where he worked on Mr. Obama’s My Brother’s Keeper Task Force, an initiative that addresses opportunity gaps faced by boys and young men of color.

Adeze Enekwechi, MD, president of Impaq and associate professor at the George Washington University, Washington, worked with Dr. Webb at the White House. “This is the place where he will have the most impact. We’ve been talking and writing about health equity ever since our time [there]. Not everybody can speak that language. Being an African American male physician and an attorney can really help drive change by being the right person at the table.”
 

Why here? Why now?

Dr. Webb sees patients 2-3 days a week on alternating weeks and knows well the concerns of people who struggle with health. Now he’s ready to have those conversations on a larger platform. “As a Black physician, it’s about bringing that healer mindset to these problems. It’s not about just going there to brow beat people or add to that divisive nature in Congress. You acknowledge that the problems exist, and then bridge,” he said, hoping that bridging party divides can be a catalyst for healing.

Carla Boutin-Foster, MD, associate dean, office of diversity education and research at the State University of New York, Brooklyn, has mentored Dr. Webb since 2013. With his credentials, confidence, and persistence, she believes, he will be a great representative of the medical community in D.C. “You need someone who respects the Constitution. When policy needs to be developed, you need a healer, someone who understands the science of vaccines. This is something Cam has been groomed for. It’s something he has been living and practicing for years.”

The killing of George Floyd and the uprising that ensued has opened the dialogue about racial inequality in America. Health care is not immune to racial bias, and the effects are palatable. One survey conducted by the Larry A. Green Center, in collaboration with the Primary Care Collaborative and 3rd Conversation, found that more than 40% of clinicians say Mr. Floyd’s demise has become a topic of concern among patients of all demographics.

When it comes to racism, Dr. Webb understands that he plays a critical role in moving America forward. “We have so many voices that are powerful and important in the highest level of legislation. We have to use those voices to root out the injustices in our society, like in the Breonna Taylor case. We have to do so because that is how you achieve the American dream,” he said.

The social determinants of health – or “ZIP-code risk” – has been proven to influence health outcomes, yet few physicians screen for them during patient visits. For Dr. Webb, discussing things like housing security and interpersonal violence are critical to providing care.

One of Dr. Webb’s biggest supporters is his wife of 11 years, Leigh Ann Webb, MD, MBA, an emergency medicine physician and assistant professor of emergency medicine at UVA. “He is an effective leader and a consensus builder,” she said of her husband, with whom she has two children. “There has always been something very unique and special about him and the way he engages the world. We need more thoughtful, intelligent people like him to help our country move forward.”

In addition to being the director of health policy and equity at UVA this fall, Dr. Webb plans to teach a course at UVA centered around the social determinants of health called Place Matters. “The focus is on understanding how education and housing and food insecurity all come together to cause illness,” he said. “Health doesn’t happen in hospitals and clinics. It happens in the community.”

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

On March 3 of this year, Bryant Cameron Webb, MD, JD, won two-thirds of the vote in Virginia’s Democratic primary race. In November, he’ll compete against Republican Bob Good to represent the state’s 5th Congressional District. If he succeeds, he will become the first Black physician ever elected to a seat in Congress.

Courtesy Dr. Bryant Cameron Webb

The political and social unrest across the United States in recent months has resulted in millions of people becoming more proactive: from sports arenas to the halls of Congress, the rally cry of Black Lives Matter has echoed like never before after the killing of George Floyd and Breonna Taylor at the hands of law enforcement. Dr. Webb, a practicing internist and professor at the University of Virginia, Charlottesville, is among many physicians joining the cause. If elected, he hopes to bring a unique perspective to Washington and advocate for racial equity to help combat systemic racist policies that result in health disparities.

“For me as a professor at UVA in both public health sciences and in medicine, I have a lot to bring to this moment,” he commented, “real expertise on issues that are critical to the nation. Beyond my passion for health and wellness, I have a passion for justice.”

Dr. Webb also believes that serving in Congress is a way to help his patients. “I balance the work of direct patient care and patient advocacy in different spaces,” said the Spotsylvania County native. “Working in Congress is patient advocacy to me. It’s where I can be at my highest use to the people I take care of. It is different from direct patient care. I think this [unique] background that I have is needed in Congress.”

Dr. Webb has never held an elected office before, and he’s looking to get elected in a district that voted for President Trump in the past election. He knows challenges lie ahead.
 

A calling

The field of medicine called for Dr. Webb at an early age. He credits his family doctor, a Black man, for inspiring him. “With six kids in our family, we saw the doctor frequently. Dr. Yarboro was a young Black man just a few years out of residency. My mom had supreme confidence in him, and he made us feel at ease. So I wanted to be a doctor ever since I was 5 or 6 years old.”

Dr. Webb earned a bachelor’s degree from the University of Virginia in 2005. He entered medical school at Wake Forest University, Winston-Salem, N.C., the following year. Following his third year of medical training, he heeded another calling: He took time off to attend law school. He enrolled in Loyola University of Chicago School of Law and earned his juris doctorate in 2012.

The move may seem an unexpected turn. But Dr. Webb feels his law degree enhances his work. “I think that it’s because I’m so steeped in the legal resources that folks need to navigate. I think I am able to provide better care. ... It’s a complement and helpful to me professionally, whether it’s fighting with an insurance company or with a prescription drug company.”

After law school, Dr. Webb finished his medical training at Wake Forest and moved north, where he completed an internal medicine residency at New York–Presbyterian Hospital. Then came yet another twist in Dr. Webb’s unconventional career path: in 2016, he was selected by President Obama as a White House fellow. He spent the next 2 years in Washington, where he worked on Mr. Obama’s My Brother’s Keeper Task Force, an initiative that addresses opportunity gaps faced by boys and young men of color.

Adeze Enekwechi, MD, president of Impaq and associate professor at the George Washington University, Washington, worked with Dr. Webb at the White House. “This is the place where he will have the most impact. We’ve been talking and writing about health equity ever since our time [there]. Not everybody can speak that language. Being an African American male physician and an attorney can really help drive change by being the right person at the table.”
 

Why here? Why now?

Dr. Webb sees patients 2-3 days a week on alternating weeks and knows well the concerns of people who struggle with health. Now he’s ready to have those conversations on a larger platform. “As a Black physician, it’s about bringing that healer mindset to these problems. It’s not about just going there to brow beat people or add to that divisive nature in Congress. You acknowledge that the problems exist, and then bridge,” he said, hoping that bridging party divides can be a catalyst for healing.

Carla Boutin-Foster, MD, associate dean, office of diversity education and research at the State University of New York, Brooklyn, has mentored Dr. Webb since 2013. With his credentials, confidence, and persistence, she believes, he will be a great representative of the medical community in D.C. “You need someone who respects the Constitution. When policy needs to be developed, you need a healer, someone who understands the science of vaccines. This is something Cam has been groomed for. It’s something he has been living and practicing for years.”

The killing of George Floyd and the uprising that ensued has opened the dialogue about racial inequality in America. Health care is not immune to racial bias, and the effects are palatable. One survey conducted by the Larry A. Green Center, in collaboration with the Primary Care Collaborative and 3rd Conversation, found that more than 40% of clinicians say Mr. Floyd’s demise has become a topic of concern among patients of all demographics.

When it comes to racism, Dr. Webb understands that he plays a critical role in moving America forward. “We have so many voices that are powerful and important in the highest level of legislation. We have to use those voices to root out the injustices in our society, like in the Breonna Taylor case. We have to do so because that is how you achieve the American dream,” he said.

The social determinants of health – or “ZIP-code risk” – has been proven to influence health outcomes, yet few physicians screen for them during patient visits. For Dr. Webb, discussing things like housing security and interpersonal violence are critical to providing care.

One of Dr. Webb’s biggest supporters is his wife of 11 years, Leigh Ann Webb, MD, MBA, an emergency medicine physician and assistant professor of emergency medicine at UVA. “He is an effective leader and a consensus builder,” she said of her husband, with whom she has two children. “There has always been something very unique and special about him and the way he engages the world. We need more thoughtful, intelligent people like him to help our country move forward.”

In addition to being the director of health policy and equity at UVA this fall, Dr. Webb plans to teach a course at UVA centered around the social determinants of health called Place Matters. “The focus is on understanding how education and housing and food insecurity all come together to cause illness,” he said. “Health doesn’t happen in hospitals and clinics. It happens in the community.”

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

In a national study of older Danes who had previously had a fracture and were taking bisphosphonates, the risk of having a serious though rare atypical femoral fracture (AFF) was greater after 3-5 years of bisphosphonate use.

The risk quickly dropped after patients stopped taking a bisphosphonate, which suggests that bisphosphonate “holidays” may be useful for some patients, the researchers said. These findings support previous work.

But the study also found that 34% of the AFFs occurred in patients who had not been taking a bisphosphonate. That rate is higher than the 6%-22% that has been reported by others.

Doug Bauer, MD, from the University of California, San Francisco, presented the new study findings during the virtual American Society of Bone and Mineral Research 2020 annual meeting.

“We found no clear risk factor that accounts for this increased risk [for AFFs] among those not exposed to bisphosphonates,” he said, “but we believe this was a real finding, as our study protocol ensured that the study radiologists were completely blinded to treatments received.”

Suzanne N. Morin, MD, who was not involved in this research, pointed out that the reported AFF risks related to bisphosphonate dose and cessation are in keeping with findings of other studies, including a recent large study by Dennis M. Black, MD, and colleagues that was published in the New England Journal of Medicine.

That study found that Asians are at higher risk for AFFs than White persons. Others have reported that specific femur geometry or physique and use of glucocorticoids increase AFF risk, Dr. Morin, from the Research Institute of the McGill University Health Center, Montreal, said in an interview.

The current study suggests that rheumatoid arthritis may be a risk factor, she added.

The fact that the rate of AFFs among patients who had not been exposed to bisphosphonates was higher than previously reported “may be due to differences in the method they used to ascertain the fractures or in medication use,” she speculated.

The clinical implications of research to date are that “the risk of AFF should not dissuade patients and providers from short-term use of bisphosphonates [3-5 years],” Dr. Bauer said. He noted that most patients should not take a bisphosphonate for longer than this unless they have a very high fracture risk.

Similarly, Dr. Morin said that clinicians “should consider initiating bisphosphonate in those at high risk for fractures and reevaluate their use after 3-6 years, depending on individual’s risk profile.”

AFF is serious but rare complication of bisphosphonate use

“Since first reported over 10 years ago, it has become clear that AFFs are a rare but serious complication of bisphosphonate therapy,” Dr. Bauer explained. However, there is still uncertainty about the magnitude of this risk, including the absolute risk for AFFs among adults who take bisphosphonates and those who do not.

To study this, the researchers analyzed data from national health care and pharmacy records and a radiology image database in Denmark. They identified almost 5,000 adults who were aged 50 years or older and who experienced a subtrochanteric and femoral shaft fracture during the period from 2010 to 2015. Two expert radiologists who were blinded to the patients’ clinical history or treatment identified AFF on the basis of ASBMR 2014 criteria.

The researchers compared three patient groups: 189 patients with AFF, 2,397 patients with typical subtrochanteric and femoral shaft fractures (no AFF), and35,946 adults aged older than 50 years (control persons).

Compared with patients with typical fractures, patients with AFF were younger (aged 71 vs. 77), more likely to be women (79% vs. 69%), and more likely to have RA (12% vs. 2.5%).

Compared with patients in the other two groups, those with AFF were more likely to use corticosteroids, proton pump inhibitors, statins, and hormone replacement therapy.

They were also more likely to use bisphosphonates (58%) than patients with typical subtrochanteric and femoral shaft fractures (19%) or control patients (10%).

The bisphosphonates used in Denmark at the time were mostly alendronate (85%) and rarely ibandronate (6%), intravenous zoledronic acid (5%), etidronate (3%), or risedronate (1%).
 

One-third of patients with AFFs had no bisphosphonate exposure

In this national cohort of adults aged older than 50 years, the absolute rates of AFF per 10,000 person-years were as follows: 0.07 in nonusers of bisphosphonates, 1.84 in those with 3-5 years of bisphosphonate use, and 4.63 in those with >7 years of bisphosphonate use. As a comparison, the rate of classic hip fracture was 43.8 per 10,000 person-years.

Compared with no bisphosphonate use, the relative risk for AFF was close to 40 times higher with more than 7 years of use, after adjusting for multiple confounders. The risk for AFF was also significantly higher among patients with RA or hypertension and for those who used proton pump inhibitors.

“Note that age, gender, and previous fracture were not associated with the risk of AFF” after controlling for multiple confounders, Dr. Bauer stressed.

The relative risk for AFF fell significantly after it had been withheld from use for more than 1 year.

Among the 189 patients with confirmed AFF, 64 patients (34%) had never taken a bisphosphonate.

Preliminary analysis showed that, among patients with AFF, those who had not been exposed to bisphosphonates were younger, more likely to be male, and less likely to have had a previous fracture, RA, or to have used corticosteroids, proton pump inhibitors, statins, or hormone-replacement therapy.

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Bauer and Dr. Morin disclosed no relevant financial relationships.

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

In a national study of older Danes who had previously had a fracture and were taking bisphosphonates, the risk of having a serious though rare atypical femoral fracture (AFF) was greater after 3-5 years of bisphosphonate use.

The risk quickly dropped after patients stopped taking a bisphosphonate, which suggests that bisphosphonate “holidays” may be useful for some patients, the researchers said. These findings support previous work.

But the study also found that 34% of the AFFs occurred in patients who had not been taking a bisphosphonate. That rate is higher than the 6%-22% that has been reported by others.

Doug Bauer, MD, from the University of California, San Francisco, presented the new study findings during the virtual American Society of Bone and Mineral Research 2020 annual meeting.

“We found no clear risk factor that accounts for this increased risk [for AFFs] among those not exposed to bisphosphonates,” he said, “but we believe this was a real finding, as our study protocol ensured that the study radiologists were completely blinded to treatments received.”

Suzanne N. Morin, MD, who was not involved in this research, pointed out that the reported AFF risks related to bisphosphonate dose and cessation are in keeping with findings of other studies, including a recent large study by Dennis M. Black, MD, and colleagues that was published in the New England Journal of Medicine.

That study found that Asians are at higher risk for AFFs than White persons. Others have reported that specific femur geometry or physique and use of glucocorticoids increase AFF risk, Dr. Morin, from the Research Institute of the McGill University Health Center, Montreal, said in an interview.

The current study suggests that rheumatoid arthritis may be a risk factor, she added.

The fact that the rate of AFFs among patients who had not been exposed to bisphosphonates was higher than previously reported “may be due to differences in the method they used to ascertain the fractures or in medication use,” she speculated.

The clinical implications of research to date are that “the risk of AFF should not dissuade patients and providers from short-term use of bisphosphonates [3-5 years],” Dr. Bauer said. He noted that most patients should not take a bisphosphonate for longer than this unless they have a very high fracture risk.

Similarly, Dr. Morin said that clinicians “should consider initiating bisphosphonate in those at high risk for fractures and reevaluate their use after 3-6 years, depending on individual’s risk profile.”

AFF is serious but rare complication of bisphosphonate use

“Since first reported over 10 years ago, it has become clear that AFFs are a rare but serious complication of bisphosphonate therapy,” Dr. Bauer explained. However, there is still uncertainty about the magnitude of this risk, including the absolute risk for AFFs among adults who take bisphosphonates and those who do not.

To study this, the researchers analyzed data from national health care and pharmacy records and a radiology image database in Denmark. They identified almost 5,000 adults who were aged 50 years or older and who experienced a subtrochanteric and femoral shaft fracture during the period from 2010 to 2015. Two expert radiologists who were blinded to the patients’ clinical history or treatment identified AFF on the basis of ASBMR 2014 criteria.

The researchers compared three patient groups: 189 patients with AFF, 2,397 patients with typical subtrochanteric and femoral shaft fractures (no AFF), and35,946 adults aged older than 50 years (control persons).

Compared with patients with typical fractures, patients with AFF were younger (aged 71 vs. 77), more likely to be women (79% vs. 69%), and more likely to have RA (12% vs. 2.5%).

Compared with patients in the other two groups, those with AFF were more likely to use corticosteroids, proton pump inhibitors, statins, and hormone replacement therapy.

They were also more likely to use bisphosphonates (58%) than patients with typical subtrochanteric and femoral shaft fractures (19%) or control patients (10%).

The bisphosphonates used in Denmark at the time were mostly alendronate (85%) and rarely ibandronate (6%), intravenous zoledronic acid (5%), etidronate (3%), or risedronate (1%).
 

One-third of patients with AFFs had no bisphosphonate exposure

In this national cohort of adults aged older than 50 years, the absolute rates of AFF per 10,000 person-years were as follows: 0.07 in nonusers of bisphosphonates, 1.84 in those with 3-5 years of bisphosphonate use, and 4.63 in those with >7 years of bisphosphonate use. As a comparison, the rate of classic hip fracture was 43.8 per 10,000 person-years.

Compared with no bisphosphonate use, the relative risk for AFF was close to 40 times higher with more than 7 years of use, after adjusting for multiple confounders. The risk for AFF was also significantly higher among patients with RA or hypertension and for those who used proton pump inhibitors.

“Note that age, gender, and previous fracture were not associated with the risk of AFF” after controlling for multiple confounders, Dr. Bauer stressed.

The relative risk for AFF fell significantly after it had been withheld from use for more than 1 year.

Among the 189 patients with confirmed AFF, 64 patients (34%) had never taken a bisphosphonate.

Preliminary analysis showed that, among patients with AFF, those who had not been exposed to bisphosphonates were younger, more likely to be male, and less likely to have had a previous fracture, RA, or to have used corticosteroids, proton pump inhibitors, statins, or hormone-replacement therapy.

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Bauer and Dr. Morin disclosed no relevant financial relationships.

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

In a national study of older Danes who had previously had a fracture and were taking bisphosphonates, the risk of having a serious though rare atypical femoral fracture (AFF) was greater after 3-5 years of bisphosphonate use.

The risk quickly dropped after patients stopped taking a bisphosphonate, which suggests that bisphosphonate “holidays” may be useful for some patients, the researchers said. These findings support previous work.

But the study also found that 34% of the AFFs occurred in patients who had not been taking a bisphosphonate. That rate is higher than the 6%-22% that has been reported by others.

Doug Bauer, MD, from the University of California, San Francisco, presented the new study findings during the virtual American Society of Bone and Mineral Research 2020 annual meeting.

“We found no clear risk factor that accounts for this increased risk [for AFFs] among those not exposed to bisphosphonates,” he said, “but we believe this was a real finding, as our study protocol ensured that the study radiologists were completely blinded to treatments received.”

Suzanne N. Morin, MD, who was not involved in this research, pointed out that the reported AFF risks related to bisphosphonate dose and cessation are in keeping with findings of other studies, including a recent large study by Dennis M. Black, MD, and colleagues that was published in the New England Journal of Medicine.

That study found that Asians are at higher risk for AFFs than White persons. Others have reported that specific femur geometry or physique and use of glucocorticoids increase AFF risk, Dr. Morin, from the Research Institute of the McGill University Health Center, Montreal, said in an interview.

The current study suggests that rheumatoid arthritis may be a risk factor, she added.

The fact that the rate of AFFs among patients who had not been exposed to bisphosphonates was higher than previously reported “may be due to differences in the method they used to ascertain the fractures or in medication use,” she speculated.

The clinical implications of research to date are that “the risk of AFF should not dissuade patients and providers from short-term use of bisphosphonates [3-5 years],” Dr. Bauer said. He noted that most patients should not take a bisphosphonate for longer than this unless they have a very high fracture risk.

Similarly, Dr. Morin said that clinicians “should consider initiating bisphosphonate in those at high risk for fractures and reevaluate their use after 3-6 years, depending on individual’s risk profile.”

AFF is serious but rare complication of bisphosphonate use

“Since first reported over 10 years ago, it has become clear that AFFs are a rare but serious complication of bisphosphonate therapy,” Dr. Bauer explained. However, there is still uncertainty about the magnitude of this risk, including the absolute risk for AFFs among adults who take bisphosphonates and those who do not.

To study this, the researchers analyzed data from national health care and pharmacy records and a radiology image database in Denmark. They identified almost 5,000 adults who were aged 50 years or older and who experienced a subtrochanteric and femoral shaft fracture during the period from 2010 to 2015. Two expert radiologists who were blinded to the patients’ clinical history or treatment identified AFF on the basis of ASBMR 2014 criteria.

The researchers compared three patient groups: 189 patients with AFF, 2,397 patients with typical subtrochanteric and femoral shaft fractures (no AFF), and35,946 adults aged older than 50 years (control persons).

Compared with patients with typical fractures, patients with AFF were younger (aged 71 vs. 77), more likely to be women (79% vs. 69%), and more likely to have RA (12% vs. 2.5%).

Compared with patients in the other two groups, those with AFF were more likely to use corticosteroids, proton pump inhibitors, statins, and hormone replacement therapy.

They were also more likely to use bisphosphonates (58%) than patients with typical subtrochanteric and femoral shaft fractures (19%) or control patients (10%).

The bisphosphonates used in Denmark at the time were mostly alendronate (85%) and rarely ibandronate (6%), intravenous zoledronic acid (5%), etidronate (3%), or risedronate (1%).
 

One-third of patients with AFFs had no bisphosphonate exposure

In this national cohort of adults aged older than 50 years, the absolute rates of AFF per 10,000 person-years were as follows: 0.07 in nonusers of bisphosphonates, 1.84 in those with 3-5 years of bisphosphonate use, and 4.63 in those with >7 years of bisphosphonate use. As a comparison, the rate of classic hip fracture was 43.8 per 10,000 person-years.

Compared with no bisphosphonate use, the relative risk for AFF was close to 40 times higher with more than 7 years of use, after adjusting for multiple confounders. The risk for AFF was also significantly higher among patients with RA or hypertension and for those who used proton pump inhibitors.

“Note that age, gender, and previous fracture were not associated with the risk of AFF” after controlling for multiple confounders, Dr. Bauer stressed.

The relative risk for AFF fell significantly after it had been withheld from use for more than 1 year.

Among the 189 patients with confirmed AFF, 64 patients (34%) had never taken a bisphosphonate.

Preliminary analysis showed that, among patients with AFF, those who had not been exposed to bisphosphonates were younger, more likely to be male, and less likely to have had a previous fracture, RA, or to have used corticosteroids, proton pump inhibitors, statins, or hormone-replacement therapy.

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Bauer and Dr. Morin disclosed no relevant financial relationships.

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

The antibody-drug conjugate sacituzumab govitecan (SG, Trodelvy) significantly extends both progression-free survival and overall survival for patients with metastatic triple-negative breast cancer (TNBC) that has progressed after multiple lines of therapy, according to phase 3 trial data.

The first-in-class drug is directed at trophoblast cell surface antigen 2 (Trop-2), which is highly expressed in breast cancer. Research on the drug was presented at the European Society for Medical Oncology Virtual Congress 2020.

ASCENT randomly assigned more than 500 patients who had metastatic TNBC and who had experienced disease progression after a median of four lines of therapy to receive either SG or physician’s choice of chemotherapy. SG significantly improved median progression-free survival (5.6 vs 1.7 months; hazard ratio [HR], 0.41; P < .0001) and median overall survival (12.1 vs 6.7 months; HR, 0.48; P < .0001).

The response rate was 35% for SG vs 5% for chemotherapy (P < .0001).

The study was presented by Aditya Bardia, MD, MPH, a medical oncologist at Massachusetts General Hospital, Boston, Massachusetts.

He said that because the safety profile of SG is consistent with previous reports and the treatment discontinuation rate was low, the clinical benefit “confirms the use of sacituzumab govitecan” in metastatic TNBC. This was a reference to the fact that the drug previously received accelerated approval on the basis of early data.

Bardia added that ongoing studies are evaluating the use of SG in earlier lines of therapy, including neoadjuvant settings in combination with other targeted agents, as well as in hormone receptor–positive metastatic breast cancer. One such study is the phase 3 TROPiCS-02 study, which is actively accruing patients.

Invited discussant Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal, said the treatment algorithm for the management of TNBC will need to be updated in light of these results.

“In my opinion, we should now add sacituzumab govitecan as a new treatment option for patients treated with two or more lines of therapy,” she said.

She noted that the study design raised some questions over the way such trials should be conducted and the future sequencing of treatments.
 

Objections to study design and execution

Discussant Cardoso said the choice of progression-free survival as the primary endpoint for the trial was not ideal.

“In the metastatic setting, and particularly for triple-negative breast cancer, where the median survival is quite low and where each line of treatment, particularly after the second line, has a short duration, the primary endpoint should have been overall survival,” she commented.

“Luckily, we saw some results, but we could have missed it,” Cardoso said. She made “a plea to make sure that overall survival is at least the co–primary endpoint” in the future.

Cardoso also said it was not clear to her why the trial had to be stopped. “For the current patients, if there is no crossover, there is no benefit in stopping the trial,” she said.

She went on: “For future patients, it’s better to have the final results sufficiently powered.” She noted that the benefit seen in ASCENT was “moderate” and “so not a substantial breakthrough.” She added that it was “important not to stop trials too early.”

On the positive side, Cardoso said the median number of previous lines of therapy was “quite remarkable for this subtype, and it is important then for us to discuss sequencing,” particularly given that so many patients received checkpoint inhibitors before entering the trial.
 

Safety and a focus on diarrhea

Investigator Bardia explained that SG is an antibody-drug conjugate directed at Trop-2, which is highly expressed in breast cancer.

The antibody is linked to SN-38, the active metabolite of irinotecan, via a hydrolyzable linker that makes internalization and enzymatic cleavage by tumor cells unnecessary.

Hydrolysis of the linker releases SN-38 both within the tumor cell and extracellularly to induce a so-called bystander effect, in which neighboring tumors cells may be killed even if they do not express Trop-2.

On the basis of positive results from phase 1/2 trial data, SG was granted accelerated approval by the US Food and Drug Administration for patients with metastatic TNBC who experience disease progression after at least two prior therapies.

ASCENT was therefore a phase 3 confirmatory study. Patients with metastatic TNBC who had received at least two prior chemotherapy regimens were randomly assigned in a 1:1 ratio to receive intravenous SG on days 1 and 8 of a 21-day cycle or to receive physician’s choice of treatment.

Physicians could choose eribulin, vinorelbine, gemcitabine, or capecitabine.

The patients continued receiving treatment until disease progression or unacceptable toxicity occurred. On the unanimous recommendation of the data safety monitoring committee, the trial was ended early because of “compelling evidence of efficacy.”

In all, 267 patients were randomly assigned to receive SG. Of those patients, 15 remain on treatment. Treatment was discontinued for 199 patients who experienced disease progression. In the control arm, 262 patients were included, none of whom are still on treatment; 166 discontinued because of disease progression.

The current analysis is limited to 235 patients in the SG group and, in the control arm, 233 patients who did not have brain metastases. Patients with brain metastases will be the subject of a later analysis.

All but one patient in both treatment groups were women. The median age was approximately 54 years. The median number of prior treatment regimens was four. All patients had previously received chemotherapy, and between 26% and 29% have taken checkpoint inhibitors.

By the data cutoff of March 11, 2020, patients had received a median of seven treatment cycles with SG. Progression-free survival was adjudicated by blind, independent central review. The median duration of response was of borderline significance, at 6.3 months vs 3.6 months (P = .057).

Bardia showed that the results were consistent among all subgroups, including subgroups determined on the basis of age, number of prior therapies, whether patients had received prior immune checkpoint therapy, and the presence of liver metastases.

With respect to safety, the important grade 3 or higher treatment-related adverse events were neutropenia (seen in 51% of SG patients vs 33% of patients in the control arm), diarrhea (10% vs <1%), leukopenia (10% vs 5%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%).

Despite the fact that the adverse event rate was higher with SG than with physician’s choice of chemotherapy, the percentage of such events that led to treatment discontinuation was numerically lower, at 4.7% vs 5.4%.

Cardoso highlighted the “substantial percentage” of patients with diarrhea and nausea in the trial and noted that “all grades” of these adverse events “affect quality of life.”

The focus therefore should be on patient education, prophylaxis, and “the early management of side effects,” she said.

This point was taken up in the postpresentation debate. Bardia said the high rate of diarrhea “likely relates to the toxic payload, which is SN-38, which is known to cause diarrhea.

“Loperamide or immodium prophylaxis can be used in patients who receive this drug, and in general, our experience with the use of sacituzumab govitecan is you can control the diarrhea,” Bardia said.

He added: “There is also a different side effect that occurs during the infusion of SG, which is abdominal cramping and diarrhea, and that’s more of a cholinergic reaction. For that, atropine is the best medication to use.”

The study was funded by Immunomedics Inc. Bardia has disclosed financial ties with Immunomedics and multiple other pharmaceutical companies. Cardoso has disclosed financial ties to multiple drug companies.
 

This article first appeared on Medscape.com.

The antibody-drug conjugate sacituzumab govitecan (SG, Trodelvy) significantly extends both progression-free survival and overall survival for patients with metastatic triple-negative breast cancer (TNBC) that has progressed after multiple lines of therapy, according to phase 3 trial data.

The first-in-class drug is directed at trophoblast cell surface antigen 2 (Trop-2), which is highly expressed in breast cancer. Research on the drug was presented at the European Society for Medical Oncology Virtual Congress 2020.

ASCENT randomly assigned more than 500 patients who had metastatic TNBC and who had experienced disease progression after a median of four lines of therapy to receive either SG or physician’s choice of chemotherapy. SG significantly improved median progression-free survival (5.6 vs 1.7 months; hazard ratio [HR], 0.41; P < .0001) and median overall survival (12.1 vs 6.7 months; HR, 0.48; P < .0001).

The response rate was 35% for SG vs 5% for chemotherapy (P < .0001).

The study was presented by Aditya Bardia, MD, MPH, a medical oncologist at Massachusetts General Hospital, Boston, Massachusetts.

He said that because the safety profile of SG is consistent with previous reports and the treatment discontinuation rate was low, the clinical benefit “confirms the use of sacituzumab govitecan” in metastatic TNBC. This was a reference to the fact that the drug previously received accelerated approval on the basis of early data.

Bardia added that ongoing studies are evaluating the use of SG in earlier lines of therapy, including neoadjuvant settings in combination with other targeted agents, as well as in hormone receptor–positive metastatic breast cancer. One such study is the phase 3 TROPiCS-02 study, which is actively accruing patients.

Invited discussant Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal, said the treatment algorithm for the management of TNBC will need to be updated in light of these results.

“In my opinion, we should now add sacituzumab govitecan as a new treatment option for patients treated with two or more lines of therapy,” she said.

She noted that the study design raised some questions over the way such trials should be conducted and the future sequencing of treatments.
 

Objections to study design and execution

Discussant Cardoso said the choice of progression-free survival as the primary endpoint for the trial was not ideal.

“In the metastatic setting, and particularly for triple-negative breast cancer, where the median survival is quite low and where each line of treatment, particularly after the second line, has a short duration, the primary endpoint should have been overall survival,” she commented.

“Luckily, we saw some results, but we could have missed it,” Cardoso said. She made “a plea to make sure that overall survival is at least the co–primary endpoint” in the future.

Cardoso also said it was not clear to her why the trial had to be stopped. “For the current patients, if there is no crossover, there is no benefit in stopping the trial,” she said.

She went on: “For future patients, it’s better to have the final results sufficiently powered.” She noted that the benefit seen in ASCENT was “moderate” and “so not a substantial breakthrough.” She added that it was “important not to stop trials too early.”

On the positive side, Cardoso said the median number of previous lines of therapy was “quite remarkable for this subtype, and it is important then for us to discuss sequencing,” particularly given that so many patients received checkpoint inhibitors before entering the trial.
 

Safety and a focus on diarrhea

Investigator Bardia explained that SG is an antibody-drug conjugate directed at Trop-2, which is highly expressed in breast cancer.

The antibody is linked to SN-38, the active metabolite of irinotecan, via a hydrolyzable linker that makes internalization and enzymatic cleavage by tumor cells unnecessary.

Hydrolysis of the linker releases SN-38 both within the tumor cell and extracellularly to induce a so-called bystander effect, in which neighboring tumors cells may be killed even if they do not express Trop-2.

On the basis of positive results from phase 1/2 trial data, SG was granted accelerated approval by the US Food and Drug Administration for patients with metastatic TNBC who experience disease progression after at least two prior therapies.

ASCENT was therefore a phase 3 confirmatory study. Patients with metastatic TNBC who had received at least two prior chemotherapy regimens were randomly assigned in a 1:1 ratio to receive intravenous SG on days 1 and 8 of a 21-day cycle or to receive physician’s choice of treatment.

Physicians could choose eribulin, vinorelbine, gemcitabine, or capecitabine.

The patients continued receiving treatment until disease progression or unacceptable toxicity occurred. On the unanimous recommendation of the data safety monitoring committee, the trial was ended early because of “compelling evidence of efficacy.”

In all, 267 patients were randomly assigned to receive SG. Of those patients, 15 remain on treatment. Treatment was discontinued for 199 patients who experienced disease progression. In the control arm, 262 patients were included, none of whom are still on treatment; 166 discontinued because of disease progression.

The current analysis is limited to 235 patients in the SG group and, in the control arm, 233 patients who did not have brain metastases. Patients with brain metastases will be the subject of a later analysis.

All but one patient in both treatment groups were women. The median age was approximately 54 years. The median number of prior treatment regimens was four. All patients had previously received chemotherapy, and between 26% and 29% have taken checkpoint inhibitors.

By the data cutoff of March 11, 2020, patients had received a median of seven treatment cycles with SG. Progression-free survival was adjudicated by blind, independent central review. The median duration of response was of borderline significance, at 6.3 months vs 3.6 months (P = .057).

Bardia showed that the results were consistent among all subgroups, including subgroups determined on the basis of age, number of prior therapies, whether patients had received prior immune checkpoint therapy, and the presence of liver metastases.

With respect to safety, the important grade 3 or higher treatment-related adverse events were neutropenia (seen in 51% of SG patients vs 33% of patients in the control arm), diarrhea (10% vs <1%), leukopenia (10% vs 5%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%).

Despite the fact that the adverse event rate was higher with SG than with physician’s choice of chemotherapy, the percentage of such events that led to treatment discontinuation was numerically lower, at 4.7% vs 5.4%.

Cardoso highlighted the “substantial percentage” of patients with diarrhea and nausea in the trial and noted that “all grades” of these adverse events “affect quality of life.”

The focus therefore should be on patient education, prophylaxis, and “the early management of side effects,” she said.

This point was taken up in the postpresentation debate. Bardia said the high rate of diarrhea “likely relates to the toxic payload, which is SN-38, which is known to cause diarrhea.

“Loperamide or immodium prophylaxis can be used in patients who receive this drug, and in general, our experience with the use of sacituzumab govitecan is you can control the diarrhea,” Bardia said.

He added: “There is also a different side effect that occurs during the infusion of SG, which is abdominal cramping and diarrhea, and that’s more of a cholinergic reaction. For that, atropine is the best medication to use.”

The study was funded by Immunomedics Inc. Bardia has disclosed financial ties with Immunomedics and multiple other pharmaceutical companies. Cardoso has disclosed financial ties to multiple drug companies.
 

This article first appeared on Medscape.com.

The antibody-drug conjugate sacituzumab govitecan (SG, Trodelvy) significantly extends both progression-free survival and overall survival for patients with metastatic triple-negative breast cancer (TNBC) that has progressed after multiple lines of therapy, according to phase 3 trial data.

The first-in-class drug is directed at trophoblast cell surface antigen 2 (Trop-2), which is highly expressed in breast cancer. Research on the drug was presented at the European Society for Medical Oncology Virtual Congress 2020.

ASCENT randomly assigned more than 500 patients who had metastatic TNBC and who had experienced disease progression after a median of four lines of therapy to receive either SG or physician’s choice of chemotherapy. SG significantly improved median progression-free survival (5.6 vs 1.7 months; hazard ratio [HR], 0.41; P < .0001) and median overall survival (12.1 vs 6.7 months; HR, 0.48; P < .0001).

The response rate was 35% for SG vs 5% for chemotherapy (P < .0001).

The study was presented by Aditya Bardia, MD, MPH, a medical oncologist at Massachusetts General Hospital, Boston, Massachusetts.

He said that because the safety profile of SG is consistent with previous reports and the treatment discontinuation rate was low, the clinical benefit “confirms the use of sacituzumab govitecan” in metastatic TNBC. This was a reference to the fact that the drug previously received accelerated approval on the basis of early data.

Bardia added that ongoing studies are evaluating the use of SG in earlier lines of therapy, including neoadjuvant settings in combination with other targeted agents, as well as in hormone receptor–positive metastatic breast cancer. One such study is the phase 3 TROPiCS-02 study, which is actively accruing patients.

Invited discussant Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal, said the treatment algorithm for the management of TNBC will need to be updated in light of these results.

“In my opinion, we should now add sacituzumab govitecan as a new treatment option for patients treated with two or more lines of therapy,” she said.

She noted that the study design raised some questions over the way such trials should be conducted and the future sequencing of treatments.
 

Objections to study design and execution

Discussant Cardoso said the choice of progression-free survival as the primary endpoint for the trial was not ideal.

“In the metastatic setting, and particularly for triple-negative breast cancer, where the median survival is quite low and where each line of treatment, particularly after the second line, has a short duration, the primary endpoint should have been overall survival,” she commented.

“Luckily, we saw some results, but we could have missed it,” Cardoso said. She made “a plea to make sure that overall survival is at least the co–primary endpoint” in the future.

Cardoso also said it was not clear to her why the trial had to be stopped. “For the current patients, if there is no crossover, there is no benefit in stopping the trial,” she said.

She went on: “For future patients, it’s better to have the final results sufficiently powered.” She noted that the benefit seen in ASCENT was “moderate” and “so not a substantial breakthrough.” She added that it was “important not to stop trials too early.”

On the positive side, Cardoso said the median number of previous lines of therapy was “quite remarkable for this subtype, and it is important then for us to discuss sequencing,” particularly given that so many patients received checkpoint inhibitors before entering the trial.
 

Safety and a focus on diarrhea

Investigator Bardia explained that SG is an antibody-drug conjugate directed at Trop-2, which is highly expressed in breast cancer.

The antibody is linked to SN-38, the active metabolite of irinotecan, via a hydrolyzable linker that makes internalization and enzymatic cleavage by tumor cells unnecessary.

Hydrolysis of the linker releases SN-38 both within the tumor cell and extracellularly to induce a so-called bystander effect, in which neighboring tumors cells may be killed even if they do not express Trop-2.

On the basis of positive results from phase 1/2 trial data, SG was granted accelerated approval by the US Food and Drug Administration for patients with metastatic TNBC who experience disease progression after at least two prior therapies.

ASCENT was therefore a phase 3 confirmatory study. Patients with metastatic TNBC who had received at least two prior chemotherapy regimens were randomly assigned in a 1:1 ratio to receive intravenous SG on days 1 and 8 of a 21-day cycle or to receive physician’s choice of treatment.

Physicians could choose eribulin, vinorelbine, gemcitabine, or capecitabine.

The patients continued receiving treatment until disease progression or unacceptable toxicity occurred. On the unanimous recommendation of the data safety monitoring committee, the trial was ended early because of “compelling evidence of efficacy.”

In all, 267 patients were randomly assigned to receive SG. Of those patients, 15 remain on treatment. Treatment was discontinued for 199 patients who experienced disease progression. In the control arm, 262 patients were included, none of whom are still on treatment; 166 discontinued because of disease progression.

The current analysis is limited to 235 patients in the SG group and, in the control arm, 233 patients who did not have brain metastases. Patients with brain metastases will be the subject of a later analysis.

All but one patient in both treatment groups were women. The median age was approximately 54 years. The median number of prior treatment regimens was four. All patients had previously received chemotherapy, and between 26% and 29% have taken checkpoint inhibitors.

By the data cutoff of March 11, 2020, patients had received a median of seven treatment cycles with SG. Progression-free survival was adjudicated by blind, independent central review. The median duration of response was of borderline significance, at 6.3 months vs 3.6 months (P = .057).

Bardia showed that the results were consistent among all subgroups, including subgroups determined on the basis of age, number of prior therapies, whether patients had received prior immune checkpoint therapy, and the presence of liver metastases.

With respect to safety, the important grade 3 or higher treatment-related adverse events were neutropenia (seen in 51% of SG patients vs 33% of patients in the control arm), diarrhea (10% vs <1%), leukopenia (10% vs 5%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%).

Despite the fact that the adverse event rate was higher with SG than with physician’s choice of chemotherapy, the percentage of such events that led to treatment discontinuation was numerically lower, at 4.7% vs 5.4%.

Cardoso highlighted the “substantial percentage” of patients with diarrhea and nausea in the trial and noted that “all grades” of these adverse events “affect quality of life.”

The focus therefore should be on patient education, prophylaxis, and “the early management of side effects,” she said.

This point was taken up in the postpresentation debate. Bardia said the high rate of diarrhea “likely relates to the toxic payload, which is SN-38, which is known to cause diarrhea.

“Loperamide or immodium prophylaxis can be used in patients who receive this drug, and in general, our experience with the use of sacituzumab govitecan is you can control the diarrhea,” Bardia said.

He added: “There is also a different side effect that occurs during the infusion of SG, which is abdominal cramping and diarrhea, and that’s more of a cholinergic reaction. For that, atropine is the best medication to use.”

The study was funded by Immunomedics Inc. Bardia has disclosed financial ties with Immunomedics and multiple other pharmaceutical companies. Cardoso has disclosed financial ties to multiple drug companies.
 

This article first appeared on Medscape.com.

References 

1. Chlebowski RT, Anderson GL, Aragaki AK, et al. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the Women’s Health Initiative randomized clinical trials. JAMA. 2020;32:369-380.
2. The North American Menopause Society. Menopause Guidebook. 8th ed. www.menopause.org/publications/consumer-publications/-em-menopause-guidebook-em-8th-edition. Accessed September 25, 2020.
3. US Preventive Services Task Force; Grossman DC, Curry SJ, Owens DK, et al. Hormone therapy for the primary prevention of chronic conditions in postmenopausal women: US Preventive Services Task Force Recommendation Statement. JAMA. 2017;318:2224-2233.

References 

1. Chlebowski RT, Anderson GL, Aragaki AK, et al. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the Women’s Health Initiative randomized clinical trials. JAMA. 2020;32:369-380.
2. The North American Menopause Society. Menopause Guidebook. 8th ed. www.menopause.org/publications/consumer-publications/-em-menopause-guidebook-em-8th-edition. Accessed September 25, 2020.
3. US Preventive Services Task Force; Grossman DC, Curry SJ, Owens DK, et al. Hormone therapy for the primary prevention of chronic conditions in postmenopausal women: US Preventive Services Task Force Recommendation Statement. JAMA. 2017;318:2224-2233.

References 

1. Chlebowski RT, Anderson GL, Aragaki AK, et al. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the Women’s Health Initiative randomized clinical trials. JAMA. 2020;32:369-380.
2. The North American Menopause Society. Menopause Guidebook. 8th ed. www.menopause.org/publications/consumer-publications/-em-menopause-guidebook-em-8th-edition. Accessed September 25, 2020.
3. US Preventive Services Task Force; Grossman DC, Curry SJ, Owens DK, et al. Hormone therapy for the primary prevention of chronic conditions in postmenopausal women: US Preventive Services Task Force Recommendation Statement. JAMA. 2017;318:2224-2233.

The Centers for Disease Control and Prevention (CDC) today abruptly deleted information from its website that it had updated Friday on how COVID-19 is spread.

The CDC had updated information on coronavirus spread and had acknowledged the prominence of aerosol transmission.

CDC’s new information still says that Sars-CoV-2 is commonly spread between people who are within about 6 feet of each other, which has been the agency’s stance for months now.

However, the deleted update had added it is spread “through respiratory droplets or small particles, such as those in aerosols, produced when an infected person coughs, sneezes, sings, talks, or breathes. These particles can be inhaled into the nose, mouth, airways, and lungs and cause infection. This is thought to be the main way the virus spreads.”

Responding to Medscape Medical News questions about the update, Jasmine Reed, spokesperson for the CDC, told Medscape Medical News, “A draft version of proposed changes to these recommendations was posted in error to the agency’s official website. CDC is currently updating its recommendations regarding airborne transmission of SARS-CoV-2 (the virus that causes COVID-19). Once this process has been completed, the updated language will be posted.”

Previous information

Previously, the CDC said the virus is spread mainly among people who are within about 6 feet of each another through respiratory droplets propelled when an infected person coughs, sneezes, or talks.

Previous guidance also said, “These droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs.”

The now deleted update said, “There is growing evidence that droplets and airborne particles can remain suspended in the air and be breathed in by others, and travel distances beyond 6 feet (for example, during choir practice, in restaurants, or in fitness classes).”

On July 6, Clinical Infectious Diseases published the paper “It Is Time to Address Airborne Transmission of Coronavirus Disease 2019,” which was supported by 239 scientists.

The authors write, “There is significant potential for inhalation exposure to viruses in microscopic respiratory droplets (microdroplets) at short to medium distances (up to several meters, or room scale).

The World Health Organization (WHO) acknowledged after this research was published that airborne transmission of the virus may play a role in infection, especially in poorly ventilated rooms and buildings, but have yet to declare aerosols as a definitive contributor.

WHO has long stated that coronavirus is spread mainly by droplets that, once expelled by coughs and sneezes of infected people, fall quickly to the floor.

The CDC update was made Friday without announcement.

“This has been one of the problems all along,” said Leana Wen, MD, an emergency physician and public health professor at George Washington University, Washington, DC. “The guidance from CDC changes on their website, but there’s no press conference, there’s no explanation of why they’re changing this now.”

Again Monday, there was no announcement that information had changed.

Update added air purifiers for prevention

The CDC continues to recommend staying 6 feet from others, washing hands, wearing a mask and routinely disinfecting frequently touched surfaces.

The update had added, “Use air purifiers to help reduce airborne germs in indoor spaces.”

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News and Nurse.com and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick

This article first appeared on Medscape.com.

The Centers for Disease Control and Prevention (CDC) today abruptly deleted information from its website that it had updated Friday on how COVID-19 is spread.

The CDC had updated information on coronavirus spread and had acknowledged the prominence of aerosol transmission.

CDC’s new information still says that Sars-CoV-2 is commonly spread between people who are within about 6 feet of each other, which has been the agency’s stance for months now.

However, the deleted update had added it is spread “through respiratory droplets or small particles, such as those in aerosols, produced when an infected person coughs, sneezes, sings, talks, or breathes. These particles can be inhaled into the nose, mouth, airways, and lungs and cause infection. This is thought to be the main way the virus spreads.”

Responding to Medscape Medical News questions about the update, Jasmine Reed, spokesperson for the CDC, told Medscape Medical News, “A draft version of proposed changes to these recommendations was posted in error to the agency’s official website. CDC is currently updating its recommendations regarding airborne transmission of SARS-CoV-2 (the virus that causes COVID-19). Once this process has been completed, the updated language will be posted.”

Previous information

Previously, the CDC said the virus is spread mainly among people who are within about 6 feet of each another through respiratory droplets propelled when an infected person coughs, sneezes, or talks.

Previous guidance also said, “These droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs.”

The now deleted update said, “There is growing evidence that droplets and airborne particles can remain suspended in the air and be breathed in by others, and travel distances beyond 6 feet (for example, during choir practice, in restaurants, or in fitness classes).”

On July 6, Clinical Infectious Diseases published the paper “It Is Time to Address Airborne Transmission of Coronavirus Disease 2019,” which was supported by 239 scientists.

The authors write, “There is significant potential for inhalation exposure to viruses in microscopic respiratory droplets (microdroplets) at short to medium distances (up to several meters, or room scale).

The World Health Organization (WHO) acknowledged after this research was published that airborne transmission of the virus may play a role in infection, especially in poorly ventilated rooms and buildings, but have yet to declare aerosols as a definitive contributor.

WHO has long stated that coronavirus is spread mainly by droplets that, once expelled by coughs and sneezes of infected people, fall quickly to the floor.

The CDC update was made Friday without announcement.

“This has been one of the problems all along,” said Leana Wen, MD, an emergency physician and public health professor at George Washington University, Washington, DC. “The guidance from CDC changes on their website, but there’s no press conference, there’s no explanation of why they’re changing this now.”

Again Monday, there was no announcement that information had changed.

Update added air purifiers for prevention

The CDC continues to recommend staying 6 feet from others, washing hands, wearing a mask and routinely disinfecting frequently touched surfaces.

The update had added, “Use air purifiers to help reduce airborne germs in indoor spaces.”

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News and Nurse.com and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick

This article first appeared on Medscape.com.

The Centers for Disease Control and Prevention (CDC) today abruptly deleted information from its website that it had updated Friday on how COVID-19 is spread.

The CDC had updated information on coronavirus spread and had acknowledged the prominence of aerosol transmission.

CDC’s new information still says that Sars-CoV-2 is commonly spread between people who are within about 6 feet of each other, which has been the agency’s stance for months now.

However, the deleted update had added it is spread “through respiratory droplets or small particles, such as those in aerosols, produced when an infected person coughs, sneezes, sings, talks, or breathes. These particles can be inhaled into the nose, mouth, airways, and lungs and cause infection. This is thought to be the main way the virus spreads.”

Responding to Medscape Medical News questions about the update, Jasmine Reed, spokesperson for the CDC, told Medscape Medical News, “A draft version of proposed changes to these recommendations was posted in error to the agency’s official website. CDC is currently updating its recommendations regarding airborne transmission of SARS-CoV-2 (the virus that causes COVID-19). Once this process has been completed, the updated language will be posted.”

Previous information

Previously, the CDC said the virus is spread mainly among people who are within about 6 feet of each another through respiratory droplets propelled when an infected person coughs, sneezes, or talks.

Previous guidance also said, “These droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs.”

The now deleted update said, “There is growing evidence that droplets and airborne particles can remain suspended in the air and be breathed in by others, and travel distances beyond 6 feet (for example, during choir practice, in restaurants, or in fitness classes).”

On July 6, Clinical Infectious Diseases published the paper “It Is Time to Address Airborne Transmission of Coronavirus Disease 2019,” which was supported by 239 scientists.

The authors write, “There is significant potential for inhalation exposure to viruses in microscopic respiratory droplets (microdroplets) at short to medium distances (up to several meters, or room scale).

The World Health Organization (WHO) acknowledged after this research was published that airborne transmission of the virus may play a role in infection, especially in poorly ventilated rooms and buildings, but have yet to declare aerosols as a definitive contributor.

WHO has long stated that coronavirus is spread mainly by droplets that, once expelled by coughs and sneezes of infected people, fall quickly to the floor.

The CDC update was made Friday without announcement.

“This has been one of the problems all along,” said Leana Wen, MD, an emergency physician and public health professor at George Washington University, Washington, DC. “The guidance from CDC changes on their website, but there’s no press conference, there’s no explanation of why they’re changing this now.”

Again Monday, there was no announcement that information had changed.

Update added air purifiers for prevention

The CDC continues to recommend staying 6 feet from others, washing hands, wearing a mask and routinely disinfecting frequently touched surfaces.

The update had added, “Use air purifiers to help reduce airborne germs in indoor spaces.”

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News and Nurse.com and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick

This article first appeared on Medscape.com.

A three-step approach may help relieve itch in patients with lichen simplex chronicus, “one of the itchiest conditions that we ever see on the vulva,” an expert advised at the virtual conference on diseases of the vulva and vagina, hosted by the International Society for the Study of Vulvovaginal Disease.

For some patients, such as those with excessive sweating or underlying psoriasis, seeing a dermatologist may be beneficial, physicians at the meeting suggested.

Treatment should aim to optimize epithelial barrier function, reduce inflammation, and stop scratching, Lynette Margesson, MD, said in a lecture at the biennial meeting, which is held by the International Society for the Study of Vulvovaginal Disease (ISSVD). “With this condition, please look always for more than one problem.”

Lichen simplex chronicus is a thick, hyperkeratotic, firm, itchy rash that can develop on top of any dermatitis. “It doesn’t show up out of nowhere,” said Dr. Margesson, an obstetrician and gynecologist at Geisel School of Medicine at Dartmouth in Hanover, N.H. “It is because of chronic rubbing and scratching on top of something else.”

It may develop on top of atopic dermatitis, psoriasis, or contact dermatitis, as well as infection, lichen sclerosus, lichen planus, or neoplasia.

Lichen simplex chronicus is characterized by years of relentless itching, and patients may wake up at night scratching. The skin looks and feels leathery, and the condition can be localized or around the entire vulva. Heat, humidity, stress, and irritants may exacerbate the condition.

Patients often try to wash the rash away with scrubbers and cleansers, which only makes it worse, Dr. Margesson said.

To get patients better, improve barrier function, such as by controlling infections, reducing sweating, avoiding irritants, and stopping excessive hygiene. Immediate therapy may include soaks, cool compresses, and ointments.

A superpotent steroid taper (e.g., clobetasol 0.05% ointment), a prednisone taper, or intramuscular triamcinolone may reduce inflammation. Dr. Margesson usually uses clobetasol, although this treatment or halobetasol can burn if patients have open skin. In such cases, she uses prednisone or intramuscular triamcinolone.

Sedating medications may help patients stop scratching, especially at night. Hydroxyzine, doxepin, or amitriptyline 2-3 hours before bedtime can help. Scratching can be a form of obsessive-compulsive disorder, and a small dose of citalopram may help during the day. Patients with significant psychological factors can be difficult to manage and tend to relapse easily, Dr. Margesson said.

If lichen simplex chronicus recurs, test for infections and allergies. “Maybe they need a mild corticosteroid all the time, like 2.5% hydrocortisone to alternate with your superpotent steroid so you can use it longer without thinning the skin,” she suggested.

Although Dr. Margesson does not often treat hyperhidrosis, addressing excessive sweating can make a big difference for patients, she said.

If a gynecologist identifies a patient who may benefit from treatment of hyperhidrosis but has limited experience with medications for this condition, it might make sense to work with a dermatologist, Aruna Venkatesan, MD, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center in San Jose, Calif., suggested during a panel discussion. Most dermatologists treat hyperhidrosis regularly, she said.

Dermatologists also may help treat patients with psoriasis who need systemic medication, Dr. Margesson said.

“In terms of ... doing the lab monitoring and knowing what side effects to look out for, your colleagues who use these medicines more are going to be more comfortable with that,” Dr. Venkatesan said. They also may have more experience navigating insurance denials to obtain a therapy. “Don’t think you are passing the buck to someone else. Sometimes that is the right thing to do, to get that help from someone else.”

Dr. Margesson is an author for UpToDate. Dr. Venkatesan had no conflicts of interest.

[email protected]

A three-step approach may help relieve itch in patients with lichen simplex chronicus, “one of the itchiest conditions that we ever see on the vulva,” an expert advised at the virtual conference on diseases of the vulva and vagina, hosted by the International Society for the Study of Vulvovaginal Disease.

For some patients, such as those with excessive sweating or underlying psoriasis, seeing a dermatologist may be beneficial, physicians at the meeting suggested.

Treatment should aim to optimize epithelial barrier function, reduce inflammation, and stop scratching, Lynette Margesson, MD, said in a lecture at the biennial meeting, which is held by the International Society for the Study of Vulvovaginal Disease (ISSVD). “With this condition, please look always for more than one problem.”

Lichen simplex chronicus is a thick, hyperkeratotic, firm, itchy rash that can develop on top of any dermatitis. “It doesn’t show up out of nowhere,” said Dr. Margesson, an obstetrician and gynecologist at Geisel School of Medicine at Dartmouth in Hanover, N.H. “It is because of chronic rubbing and scratching on top of something else.”

It may develop on top of atopic dermatitis, psoriasis, or contact dermatitis, as well as infection, lichen sclerosus, lichen planus, or neoplasia.

Lichen simplex chronicus is characterized by years of relentless itching, and patients may wake up at night scratching. The skin looks and feels leathery, and the condition can be localized or around the entire vulva. Heat, humidity, stress, and irritants may exacerbate the condition.

Patients often try to wash the rash away with scrubbers and cleansers, which only makes it worse, Dr. Margesson said.

To get patients better, improve barrier function, such as by controlling infections, reducing sweating, avoiding irritants, and stopping excessive hygiene. Immediate therapy may include soaks, cool compresses, and ointments.

A superpotent steroid taper (e.g., clobetasol 0.05% ointment), a prednisone taper, or intramuscular triamcinolone may reduce inflammation. Dr. Margesson usually uses clobetasol, although this treatment or halobetasol can burn if patients have open skin. In such cases, she uses prednisone or intramuscular triamcinolone.

Sedating medications may help patients stop scratching, especially at night. Hydroxyzine, doxepin, or amitriptyline 2-3 hours before bedtime can help. Scratching can be a form of obsessive-compulsive disorder, and a small dose of citalopram may help during the day. Patients with significant psychological factors can be difficult to manage and tend to relapse easily, Dr. Margesson said.

If lichen simplex chronicus recurs, test for infections and allergies. “Maybe they need a mild corticosteroid all the time, like 2.5% hydrocortisone to alternate with your superpotent steroid so you can use it longer without thinning the skin,” she suggested.

Although Dr. Margesson does not often treat hyperhidrosis, addressing excessive sweating can make a big difference for patients, she said.

If a gynecologist identifies a patient who may benefit from treatment of hyperhidrosis but has limited experience with medications for this condition, it might make sense to work with a dermatologist, Aruna Venkatesan, MD, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center in San Jose, Calif., suggested during a panel discussion. Most dermatologists treat hyperhidrosis regularly, she said.

Dermatologists also may help treat patients with psoriasis who need systemic medication, Dr. Margesson said.

“In terms of ... doing the lab monitoring and knowing what side effects to look out for, your colleagues who use these medicines more are going to be more comfortable with that,” Dr. Venkatesan said. They also may have more experience navigating insurance denials to obtain a therapy. “Don’t think you are passing the buck to someone else. Sometimes that is the right thing to do, to get that help from someone else.”

Dr. Margesson is an author for UpToDate. Dr. Venkatesan had no conflicts of interest.

[email protected]

A three-step approach may help relieve itch in patients with lichen simplex chronicus, “one of the itchiest conditions that we ever see on the vulva,” an expert advised at the virtual conference on diseases of the vulva and vagina, hosted by the International Society for the Study of Vulvovaginal Disease.

For some patients, such as those with excessive sweating or underlying psoriasis, seeing a dermatologist may be beneficial, physicians at the meeting suggested.

Treatment should aim to optimize epithelial barrier function, reduce inflammation, and stop scratching, Lynette Margesson, MD, said in a lecture at the biennial meeting, which is held by the International Society for the Study of Vulvovaginal Disease (ISSVD). “With this condition, please look always for more than one problem.”

Lichen simplex chronicus is a thick, hyperkeratotic, firm, itchy rash that can develop on top of any dermatitis. “It doesn’t show up out of nowhere,” said Dr. Margesson, an obstetrician and gynecologist at Geisel School of Medicine at Dartmouth in Hanover, N.H. “It is because of chronic rubbing and scratching on top of something else.”

It may develop on top of atopic dermatitis, psoriasis, or contact dermatitis, as well as infection, lichen sclerosus, lichen planus, or neoplasia.

Lichen simplex chronicus is characterized by years of relentless itching, and patients may wake up at night scratching. The skin looks and feels leathery, and the condition can be localized or around the entire vulva. Heat, humidity, stress, and irritants may exacerbate the condition.

Patients often try to wash the rash away with scrubbers and cleansers, which only makes it worse, Dr. Margesson said.

To get patients better, improve barrier function, such as by controlling infections, reducing sweating, avoiding irritants, and stopping excessive hygiene. Immediate therapy may include soaks, cool compresses, and ointments.

A superpotent steroid taper (e.g., clobetasol 0.05% ointment), a prednisone taper, or intramuscular triamcinolone may reduce inflammation. Dr. Margesson usually uses clobetasol, although this treatment or halobetasol can burn if patients have open skin. In such cases, she uses prednisone or intramuscular triamcinolone.

Sedating medications may help patients stop scratching, especially at night. Hydroxyzine, doxepin, or amitriptyline 2-3 hours before bedtime can help. Scratching can be a form of obsessive-compulsive disorder, and a small dose of citalopram may help during the day. Patients with significant psychological factors can be difficult to manage and tend to relapse easily, Dr. Margesson said.

If lichen simplex chronicus recurs, test for infections and allergies. “Maybe they need a mild corticosteroid all the time, like 2.5% hydrocortisone to alternate with your superpotent steroid so you can use it longer without thinning the skin,” she suggested.

Although Dr. Margesson does not often treat hyperhidrosis, addressing excessive sweating can make a big difference for patients, she said.

If a gynecologist identifies a patient who may benefit from treatment of hyperhidrosis but has limited experience with medications for this condition, it might make sense to work with a dermatologist, Aruna Venkatesan, MD, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center in San Jose, Calif., suggested during a panel discussion. Most dermatologists treat hyperhidrosis regularly, she said.

Dermatologists also may help treat patients with psoriasis who need systemic medication, Dr. Margesson said.

“In terms of ... doing the lab monitoring and knowing what side effects to look out for, your colleagues who use these medicines more are going to be more comfortable with that,” Dr. Venkatesan said. They also may have more experience navigating insurance denials to obtain a therapy. “Don’t think you are passing the buck to someone else. Sometimes that is the right thing to do, to get that help from someone else.”

Dr. Margesson is an author for UpToDate. Dr. Venkatesan had no conflicts of interest.

[email protected]

On Feb. 27, 2018, I got an email from the Heritage Foundation that alerted me to a news conference that afternoon held by Republican attorneys general of Texas and other states. It was referred to only as a “discussion about the Affordable Care Act lawsuit.”

Supreme Court of the United States

I sent the following note to my editor: “I’m off to the Hill anyway. I could stop by this. You never know what it might morph into.”

Few people took that case very seriously – barely a handful of reporters attended the news conference. But it has now “morphed into” the latest existential threat to the Affordable Care Act, scheduled for oral arguments at the Supreme Court a week after the general election in November. And with the death of Justice Ruth Bader Ginsburg on Friday, that case could well morph into the threat that brings down the law in its entirety.

Democrats are raising alarms about the future of the law without Ms. Ginsburg. House Speaker Nancy Pelosi, speaking on ABC’s “This Week” Sunday morning, said that part of the strategy by President Trump and Senate Republicans to quickly fill her seat was to help undermine the ACA.

“The president is rushing to make some kind of a decision because … Nov. 10 is when the arguments begin on the Affordable Care Act,” she said. “He doesn’t want to crush the virus. He wants to crush the Affordable Care Act.”

Ms. Ginsburg’s death could throw an already chaotic general election campaign during a pandemic into even more turmoil. But in the longer term, her absence from the bench could accelerate a trend underway to get cases to the Supreme Court toward invalidating the ACA and rolling back reproductive freedoms for women.

Let’s take them one at a time.
 

The ACA under fire – again

The GOP attorneys general argued in February 2018 that the Republican-sponsored tax cut bill Congress passed two months earlier had rendered the ACA unconstitutional by reducing to zero the ACA’s penalty for not having insurance. They based their argument on Chief Justice John Roberts’ 2012 conclusion that the ACA was valid, interpreting that penalty as a constitutionally appropriate tax.

Most legal scholars, including several who challenged the law before the Supreme Court in 2012 and again in 2015, find the argument that the entire law should fall to be unconvincing. “If courts invalidate an entire law merely because Congress eliminates or revises one part, as happened here, that may well inhibit necessary reform of federal legislation in the future by turning it into an ‘all or nothing’ proposition,” wrote a group of conservative and liberal law professors in a brief filed in the case.

Still, in December 2018, U.S. District Judge Reed O’Connor in Texas accepted the GOP argument and declared the law unconstitutional. In December 2019, a three-judge 5th Circuit appeals court panel in New Orleans agreed that without the penalty the requirement to buy insurance is unconstitutional. But it sent the case back to Mr. O’Connor to suggest that perhaps the entire law need not fall.

Not wanting to wait the months or years that reconsideration would take, Democratic attorneys general defending the ACA asked the Supreme Court to hear the case this year. (Democrats are defending the law in court because the Trump administration decided to support the GOP attorneys general’s case.) The court agreed to take the case but scheduled arguments for the week after the November election.

While the fate of the ACA was and is a live political issue, few legal observers were terribly worried about the legal outcome of the case, now known as Texas v. California, if only because the case seemed much weaker than the 2012 and 2015 cases in which Mr. Roberts joined the court’s four liberals. In the 2015 case, which challenged the validity of federal tax subsidies helping millions of Americans buy health insurance on the ACA’s marketplaces, both Mr. Roberts and now-retired Justice Anthony Kennedy voted to uphold the law.

But without Ms. Ginsburg, the case could wind up in a 4-4 tie, even if Mr. Roberts supports the law’s constitutionality. That could let the lower-court ruling stand, although it would not be binding on other courts outside of the 5th Circuit. The court could also put off the arguments or, if the Republican Senate replaces Ms. Ginsburg with another conservative justice before arguments are heard, Republicans could secure a 5-4 ruling against the law. Some court observers argue that Justice Brett Kavanaugh has not favored invalidating an entire statute if only part of it is flawed and might not approve overturning the ACA. Still, what started out as an effort to energize Republican voters for the 2018 midterms after Congress failed to “repeal and replace” the health law in 2017 could end up throwing the nation’s entire health system into chaos.

At least 20 million Americans – and likely many more who sought coverage since the start of the coronavirus pandemic — who buy insurance through the ACA marketplaces or have Medicaid through the law’s expansion could lose coverage right away. Many millions more would lose the law’s popular protections guaranteeing coverage for people with preexisting health conditions, including those who have had COVID-19.

Adult children under age 26 years would no longer be guaranteed the right to remain on their parents’ health plans, and Medicare patients would lose enhanced prescription drug coverage. Women would lose guaranteed access to birth control at no out-of-pocket cost.

But a sudden elimination would affect more than just health care consumers. Insurance companies, drug companies, hospitals, and doctors have all changed the way they do business because of incentives and penalties in the health law. If it’s struck down, many of the “rules of the road” would literally be wiped away, including billing and payment mechanisms.

A new Democratic president could not drop the lawsuit because the Trump administration is not the plaintiff (the GOP attorneys general are). But a Democratic Congress and president could in theory make the entire issue go away by reinstating the penalty for failure to have insurance, even at a minimal amount. However, as far as the health law goes, for now, nothing is a sure thing.

As Nicholas Bagley, a law professor at the University of Michigan, Ann Arbor, who specializes in health issues, tweeted: “Among other things, the Affordable Care Act now dangles from a thread.”
 

Reproductive rights

A woman’s right to abortion – and even to birth control – also has been hanging by a thread at the high court for more than a decade. This past term, Mr. Roberts joined the liberals to invalidate a Louisiana law that would have closed most of the state’s abortion clinics, but he made it clear it was not a vote for abortion rights. The Louisiana law was too similar to a Texas law the court (without his vote) struck down in 2016, Mr. Roberts argued.

Ms. Ginsburg had been a stalwart supporter of reproductive freedom for women. In her nearly 3 decades on the court, she always voted with backers of abortion rights and birth control and led the dissenters in 2007 when the court upheld a federal ban on a specific abortion procedure.

Adding a justice opposed to abortion to the bench – which is what Trump has promised his supporters – would almost certainly tilt the court in favor of far more dramatic restrictions on the procedure and possibly an overturn of the landmark 1973 ruling Roe v. Wade.

But not only is abortion on the line: The court in recent years has repeatedly ruled that employers with religious objections can refuse to provide contraception.

And waiting in the lower-court pipeline are cases involving federal funding of Planned Parenthood in both the Medicaid and federal family planning programs, and the ability of individual health workers to decline to participate in abortion and other procedures.

For Ms. Ginsburg, those issues came down to a clear question of a woman’s guarantee of equal status under the law.

“Women, it is now acknowledged, have the talent, capacity, and right ‘to participate equally in the economic and social life of the Nation,’ ” she wrote in her dissent in that 2007 abortion case. “Their ability to realize their full potential, the Court recognized, is intimately connected to ‘their ability to control their reproductive lives.’ ”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

On Feb. 27, 2018, I got an email from the Heritage Foundation that alerted me to a news conference that afternoon held by Republican attorneys general of Texas and other states. It was referred to only as a “discussion about the Affordable Care Act lawsuit.”

Supreme Court of the United States

I sent the following note to my editor: “I’m off to the Hill anyway. I could stop by this. You never know what it might morph into.”

Few people took that case very seriously – barely a handful of reporters attended the news conference. But it has now “morphed into” the latest existential threat to the Affordable Care Act, scheduled for oral arguments at the Supreme Court a week after the general election in November. And with the death of Justice Ruth Bader Ginsburg on Friday, that case could well morph into the threat that brings down the law in its entirety.

Democrats are raising alarms about the future of the law without Ms. Ginsburg. House Speaker Nancy Pelosi, speaking on ABC’s “This Week” Sunday morning, said that part of the strategy by President Trump and Senate Republicans to quickly fill her seat was to help undermine the ACA.

“The president is rushing to make some kind of a decision because … Nov. 10 is when the arguments begin on the Affordable Care Act,” she said. “He doesn’t want to crush the virus. He wants to crush the Affordable Care Act.”

Ms. Ginsburg’s death could throw an already chaotic general election campaign during a pandemic into even more turmoil. But in the longer term, her absence from the bench could accelerate a trend underway to get cases to the Supreme Court toward invalidating the ACA and rolling back reproductive freedoms for women.

Let’s take them one at a time.
 

The ACA under fire – again

The GOP attorneys general argued in February 2018 that the Republican-sponsored tax cut bill Congress passed two months earlier had rendered the ACA unconstitutional by reducing to zero the ACA’s penalty for not having insurance. They based their argument on Chief Justice John Roberts’ 2012 conclusion that the ACA was valid, interpreting that penalty as a constitutionally appropriate tax.

Most legal scholars, including several who challenged the law before the Supreme Court in 2012 and again in 2015, find the argument that the entire law should fall to be unconvincing. “If courts invalidate an entire law merely because Congress eliminates or revises one part, as happened here, that may well inhibit necessary reform of federal legislation in the future by turning it into an ‘all or nothing’ proposition,” wrote a group of conservative and liberal law professors in a brief filed in the case.

Still, in December 2018, U.S. District Judge Reed O’Connor in Texas accepted the GOP argument and declared the law unconstitutional. In December 2019, a three-judge 5th Circuit appeals court panel in New Orleans agreed that without the penalty the requirement to buy insurance is unconstitutional. But it sent the case back to Mr. O’Connor to suggest that perhaps the entire law need not fall.

Not wanting to wait the months or years that reconsideration would take, Democratic attorneys general defending the ACA asked the Supreme Court to hear the case this year. (Democrats are defending the law in court because the Trump administration decided to support the GOP attorneys general’s case.) The court agreed to take the case but scheduled arguments for the week after the November election.

While the fate of the ACA was and is a live political issue, few legal observers were terribly worried about the legal outcome of the case, now known as Texas v. California, if only because the case seemed much weaker than the 2012 and 2015 cases in which Mr. Roberts joined the court’s four liberals. In the 2015 case, which challenged the validity of federal tax subsidies helping millions of Americans buy health insurance on the ACA’s marketplaces, both Mr. Roberts and now-retired Justice Anthony Kennedy voted to uphold the law.

But without Ms. Ginsburg, the case could wind up in a 4-4 tie, even if Mr. Roberts supports the law’s constitutionality. That could let the lower-court ruling stand, although it would not be binding on other courts outside of the 5th Circuit. The court could also put off the arguments or, if the Republican Senate replaces Ms. Ginsburg with another conservative justice before arguments are heard, Republicans could secure a 5-4 ruling against the law. Some court observers argue that Justice Brett Kavanaugh has not favored invalidating an entire statute if only part of it is flawed and might not approve overturning the ACA. Still, what started out as an effort to energize Republican voters for the 2018 midterms after Congress failed to “repeal and replace” the health law in 2017 could end up throwing the nation’s entire health system into chaos.

At least 20 million Americans – and likely many more who sought coverage since the start of the coronavirus pandemic — who buy insurance through the ACA marketplaces or have Medicaid through the law’s expansion could lose coverage right away. Many millions more would lose the law’s popular protections guaranteeing coverage for people with preexisting health conditions, including those who have had COVID-19.

Adult children under age 26 years would no longer be guaranteed the right to remain on their parents’ health plans, and Medicare patients would lose enhanced prescription drug coverage. Women would lose guaranteed access to birth control at no out-of-pocket cost.

But a sudden elimination would affect more than just health care consumers. Insurance companies, drug companies, hospitals, and doctors have all changed the way they do business because of incentives and penalties in the health law. If it’s struck down, many of the “rules of the road” would literally be wiped away, including billing and payment mechanisms.

A new Democratic president could not drop the lawsuit because the Trump administration is not the plaintiff (the GOP attorneys general are). But a Democratic Congress and president could in theory make the entire issue go away by reinstating the penalty for failure to have insurance, even at a minimal amount. However, as far as the health law goes, for now, nothing is a sure thing.

As Nicholas Bagley, a law professor at the University of Michigan, Ann Arbor, who specializes in health issues, tweeted: “Among other things, the Affordable Care Act now dangles from a thread.”
 

Reproductive rights

A woman’s right to abortion – and even to birth control – also has been hanging by a thread at the high court for more than a decade. This past term, Mr. Roberts joined the liberals to invalidate a Louisiana law that would have closed most of the state’s abortion clinics, but he made it clear it was not a vote for abortion rights. The Louisiana law was too similar to a Texas law the court (without his vote) struck down in 2016, Mr. Roberts argued.

Ms. Ginsburg had been a stalwart supporter of reproductive freedom for women. In her nearly 3 decades on the court, she always voted with backers of abortion rights and birth control and led the dissenters in 2007 when the court upheld a federal ban on a specific abortion procedure.

Adding a justice opposed to abortion to the bench – which is what Trump has promised his supporters – would almost certainly tilt the court in favor of far more dramatic restrictions on the procedure and possibly an overturn of the landmark 1973 ruling Roe v. Wade.

But not only is abortion on the line: The court in recent years has repeatedly ruled that employers with religious objections can refuse to provide contraception.

And waiting in the lower-court pipeline are cases involving federal funding of Planned Parenthood in both the Medicaid and federal family planning programs, and the ability of individual health workers to decline to participate in abortion and other procedures.

For Ms. Ginsburg, those issues came down to a clear question of a woman’s guarantee of equal status under the law.

“Women, it is now acknowledged, have the talent, capacity, and right ‘to participate equally in the economic and social life of the Nation,’ ” she wrote in her dissent in that 2007 abortion case. “Their ability to realize their full potential, the Court recognized, is intimately connected to ‘their ability to control their reproductive lives.’ ”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

On Feb. 27, 2018, I got an email from the Heritage Foundation that alerted me to a news conference that afternoon held by Republican attorneys general of Texas and other states. It was referred to only as a “discussion about the Affordable Care Act lawsuit.”

Supreme Court of the United States

I sent the following note to my editor: “I’m off to the Hill anyway. I could stop by this. You never know what it might morph into.”

Few people took that case very seriously – barely a handful of reporters attended the news conference. But it has now “morphed into” the latest existential threat to the Affordable Care Act, scheduled for oral arguments at the Supreme Court a week after the general election in November. And with the death of Justice Ruth Bader Ginsburg on Friday, that case could well morph into the threat that brings down the law in its entirety.

Democrats are raising alarms about the future of the law without Ms. Ginsburg. House Speaker Nancy Pelosi, speaking on ABC’s “This Week” Sunday morning, said that part of the strategy by President Trump and Senate Republicans to quickly fill her seat was to help undermine the ACA.

“The president is rushing to make some kind of a decision because … Nov. 10 is when the arguments begin on the Affordable Care Act,” she said. “He doesn’t want to crush the virus. He wants to crush the Affordable Care Act.”

Ms. Ginsburg’s death could throw an already chaotic general election campaign during a pandemic into even more turmoil. But in the longer term, her absence from the bench could accelerate a trend underway to get cases to the Supreme Court toward invalidating the ACA and rolling back reproductive freedoms for women.

Let’s take them one at a time.
 

The ACA under fire – again

The GOP attorneys general argued in February 2018 that the Republican-sponsored tax cut bill Congress passed two months earlier had rendered the ACA unconstitutional by reducing to zero the ACA’s penalty for not having insurance. They based their argument on Chief Justice John Roberts’ 2012 conclusion that the ACA was valid, interpreting that penalty as a constitutionally appropriate tax.

Most legal scholars, including several who challenged the law before the Supreme Court in 2012 and again in 2015, find the argument that the entire law should fall to be unconvincing. “If courts invalidate an entire law merely because Congress eliminates or revises one part, as happened here, that may well inhibit necessary reform of federal legislation in the future by turning it into an ‘all or nothing’ proposition,” wrote a group of conservative and liberal law professors in a brief filed in the case.

Still, in December 2018, U.S. District Judge Reed O’Connor in Texas accepted the GOP argument and declared the law unconstitutional. In December 2019, a three-judge 5th Circuit appeals court panel in New Orleans agreed that without the penalty the requirement to buy insurance is unconstitutional. But it sent the case back to Mr. O’Connor to suggest that perhaps the entire law need not fall.

Not wanting to wait the months or years that reconsideration would take, Democratic attorneys general defending the ACA asked the Supreme Court to hear the case this year. (Democrats are defending the law in court because the Trump administration decided to support the GOP attorneys general’s case.) The court agreed to take the case but scheduled arguments for the week after the November election.

While the fate of the ACA was and is a live political issue, few legal observers were terribly worried about the legal outcome of the case, now known as Texas v. California, if only because the case seemed much weaker than the 2012 and 2015 cases in which Mr. Roberts joined the court’s four liberals. In the 2015 case, which challenged the validity of federal tax subsidies helping millions of Americans buy health insurance on the ACA’s marketplaces, both Mr. Roberts and now-retired Justice Anthony Kennedy voted to uphold the law.

But without Ms. Ginsburg, the case could wind up in a 4-4 tie, even if Mr. Roberts supports the law’s constitutionality. That could let the lower-court ruling stand, although it would not be binding on other courts outside of the 5th Circuit. The court could also put off the arguments or, if the Republican Senate replaces Ms. Ginsburg with another conservative justice before arguments are heard, Republicans could secure a 5-4 ruling against the law. Some court observers argue that Justice Brett Kavanaugh has not favored invalidating an entire statute if only part of it is flawed and might not approve overturning the ACA. Still, what started out as an effort to energize Republican voters for the 2018 midterms after Congress failed to “repeal and replace” the health law in 2017 could end up throwing the nation’s entire health system into chaos.

At least 20 million Americans – and likely many more who sought coverage since the start of the coronavirus pandemic — who buy insurance through the ACA marketplaces or have Medicaid through the law’s expansion could lose coverage right away. Many millions more would lose the law’s popular protections guaranteeing coverage for people with preexisting health conditions, including those who have had COVID-19.

Adult children under age 26 years would no longer be guaranteed the right to remain on their parents’ health plans, and Medicare patients would lose enhanced prescription drug coverage. Women would lose guaranteed access to birth control at no out-of-pocket cost.

But a sudden elimination would affect more than just health care consumers. Insurance companies, drug companies, hospitals, and doctors have all changed the way they do business because of incentives and penalties in the health law. If it’s struck down, many of the “rules of the road” would literally be wiped away, including billing and payment mechanisms.

A new Democratic president could not drop the lawsuit because the Trump administration is not the plaintiff (the GOP attorneys general are). But a Democratic Congress and president could in theory make the entire issue go away by reinstating the penalty for failure to have insurance, even at a minimal amount. However, as far as the health law goes, for now, nothing is a sure thing.

As Nicholas Bagley, a law professor at the University of Michigan, Ann Arbor, who specializes in health issues, tweeted: “Among other things, the Affordable Care Act now dangles from a thread.”
 

Reproductive rights

A woman’s right to abortion – and even to birth control – also has been hanging by a thread at the high court for more than a decade. This past term, Mr. Roberts joined the liberals to invalidate a Louisiana law that would have closed most of the state’s abortion clinics, but he made it clear it was not a vote for abortion rights. The Louisiana law was too similar to a Texas law the court (without his vote) struck down in 2016, Mr. Roberts argued.

Ms. Ginsburg had been a stalwart supporter of reproductive freedom for women. In her nearly 3 decades on the court, she always voted with backers of abortion rights and birth control and led the dissenters in 2007 when the court upheld a federal ban on a specific abortion procedure.

Adding a justice opposed to abortion to the bench – which is what Trump has promised his supporters – would almost certainly tilt the court in favor of far more dramatic restrictions on the procedure and possibly an overturn of the landmark 1973 ruling Roe v. Wade.

But not only is abortion on the line: The court in recent years has repeatedly ruled that employers with religious objections can refuse to provide contraception.

And waiting in the lower-court pipeline are cases involving federal funding of Planned Parenthood in both the Medicaid and federal family planning programs, and the ability of individual health workers to decline to participate in abortion and other procedures.

For Ms. Ginsburg, those issues came down to a clear question of a woman’s guarantee of equal status under the law.

“Women, it is now acknowledged, have the talent, capacity, and right ‘to participate equally in the economic and social life of the Nation,’ ” she wrote in her dissent in that 2007 abortion case. “Their ability to realize their full potential, the Court recognized, is intimately connected to ‘their ability to control their reproductive lives.’ ”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Key clinical point: Pembrolizumab plus eribulin did not outperform eribulin alone among patients with heavily pretreated, HR-positive, ERBB2-negative metastatic breast cancer.

Major finding: After a median of 10.5 months of follow-up, combination therapy did not improve PFS or OS in the intention-to-treat population or in the subgroup of PD-L1 positive patients.

Study details: Multicenter randomized trial of 88 patients with HR-positive, ERBB2-negative metastatic breast cancer who had received >2 lines of hormonal therapy and 0-2 lines of chemotherapy.

Disclosures: Merck & Co providing study funding and pembrolizumab. Eisai provided eribulin. Several investigators disclosed ties to Merck, Eisai, and other pharmaceutical companies.

Citation: Tolaney SM et al. Jama Oncol. 2020 Sep 3. doi: 10.1001/jamaoncol.2020.3524

Key clinical point: Pembrolizumab plus eribulin did not outperform eribulin alone among patients with heavily pretreated, HR-positive, ERBB2-negative metastatic breast cancer.

Major finding: After a median of 10.5 months of follow-up, combination therapy did not improve PFS or OS in the intention-to-treat population or in the subgroup of PD-L1 positive patients.

Study details: Multicenter randomized trial of 88 patients with HR-positive, ERBB2-negative metastatic breast cancer who had received >2 lines of hormonal therapy and 0-2 lines of chemotherapy.

Disclosures: Merck & Co providing study funding and pembrolizumab. Eisai provided eribulin. Several investigators disclosed ties to Merck, Eisai, and other pharmaceutical companies.

Citation: Tolaney SM et al. Jama Oncol. 2020 Sep 3. doi: 10.1001/jamaoncol.2020.3524

Key clinical point: Pembrolizumab plus eribulin did not outperform eribulin alone among patients with heavily pretreated, HR-positive, ERBB2-negative metastatic breast cancer.

Major finding: After a median of 10.5 months of follow-up, combination therapy did not improve PFS or OS in the intention-to-treat population or in the subgroup of PD-L1 positive patients.

Study details: Multicenter randomized trial of 88 patients with HR-positive, ERBB2-negative metastatic breast cancer who had received >2 lines of hormonal therapy and 0-2 lines of chemotherapy.

Disclosures: Merck & Co providing study funding and pembrolizumab. Eisai provided eribulin. Several investigators disclosed ties to Merck, Eisai, and other pharmaceutical companies.

Citation: Tolaney SM et al. Jama Oncol. 2020 Sep 3. doi: 10.1001/jamaoncol.2020.3524