News from the FDA/CDC

The Food and Drug Administration has approved brigatinib (Alunbrig) to treat adults with ALK-positive metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The FDA also approved the Vysis ALK Break Apart FISH Probe Kit as a companion diagnostic for brigatinib.

Brigatinib and the companion diagnostic were both evaluated in the ALTA 1L trial (NCT02737501). The trial enrolled adults with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy. Patients had to have an ALK rearrangement based on a local standard of care test.

Clinical samples from trial participants were retrospectively tested with the Vysis ALK Break Apart FISH Probe Kit. Of the 275 patients enrolled in the trial, 239 were ALK positive according to the test. Results were negative for 20 patients and unavailable for 16 patients.

Patients were randomized to receive brigatinib at 180 mg once daily with a 7-day lead-in at 90 mg once daily (n = 137) or crizotinib at 250 mg twice daily (n = 138).

The estimated median progression-free survival was 24 months in the brigatinib arm and 11 months in the crizotinib arm (hazard ratio, 0.49; P < .0001). The overall response rate was 74% in the brigatinib arm and 62% in the crizotinib arm.

The most common adverse events in the brigatinib arm, occurring in at least 20% of patients, were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, abdominal pain, pruritus, back pain, and dyspnea.

Serious adverse events occurred in 33% of patients in the brigatinib arm, and fatal adverse events included in 2.9%. The fatal events were pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).

For more details on the ALTA 1L trial, see the full prescribing information for brigatinib.

The approval of brigatinib was granted to ARIAD Pharmaceuticals. The approval of the Vysis ALK Break Apart FISH Probe Kit was granted to Abbott Molecular.

The Food and Drug Administration has approved brigatinib (Alunbrig) to treat adults with ALK-positive metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The FDA also approved the Vysis ALK Break Apart FISH Probe Kit as a companion diagnostic for brigatinib.

Brigatinib and the companion diagnostic were both evaluated in the ALTA 1L trial (NCT02737501). The trial enrolled adults with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy. Patients had to have an ALK rearrangement based on a local standard of care test.

Clinical samples from trial participants were retrospectively tested with the Vysis ALK Break Apart FISH Probe Kit. Of the 275 patients enrolled in the trial, 239 were ALK positive according to the test. Results were negative for 20 patients and unavailable for 16 patients.

Patients were randomized to receive brigatinib at 180 mg once daily with a 7-day lead-in at 90 mg once daily (n = 137) or crizotinib at 250 mg twice daily (n = 138).

The estimated median progression-free survival was 24 months in the brigatinib arm and 11 months in the crizotinib arm (hazard ratio, 0.49; P < .0001). The overall response rate was 74% in the brigatinib arm and 62% in the crizotinib arm.

The most common adverse events in the brigatinib arm, occurring in at least 20% of patients, were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, abdominal pain, pruritus, back pain, and dyspnea.

Serious adverse events occurred in 33% of patients in the brigatinib arm, and fatal adverse events included in 2.9%. The fatal events were pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).

For more details on the ALTA 1L trial, see the full prescribing information for brigatinib.

The approval of brigatinib was granted to ARIAD Pharmaceuticals. The approval of the Vysis ALK Break Apart FISH Probe Kit was granted to Abbott Molecular.

The Food and Drug Administration has approved brigatinib (Alunbrig) to treat adults with ALK-positive metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The FDA also approved the Vysis ALK Break Apart FISH Probe Kit as a companion diagnostic for brigatinib.

Brigatinib and the companion diagnostic were both evaluated in the ALTA 1L trial (NCT02737501). The trial enrolled adults with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy. Patients had to have an ALK rearrangement based on a local standard of care test.

Clinical samples from trial participants were retrospectively tested with the Vysis ALK Break Apart FISH Probe Kit. Of the 275 patients enrolled in the trial, 239 were ALK positive according to the test. Results were negative for 20 patients and unavailable for 16 patients.

Patients were randomized to receive brigatinib at 180 mg once daily with a 7-day lead-in at 90 mg once daily (n = 137) or crizotinib at 250 mg twice daily (n = 138).

The estimated median progression-free survival was 24 months in the brigatinib arm and 11 months in the crizotinib arm (hazard ratio, 0.49; P < .0001). The overall response rate was 74% in the brigatinib arm and 62% in the crizotinib arm.

The most common adverse events in the brigatinib arm, occurring in at least 20% of patients, were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, abdominal pain, pruritus, back pain, and dyspnea.

Serious adverse events occurred in 33% of patients in the brigatinib arm, and fatal adverse events included in 2.9%. The fatal events were pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).

For more details on the ALTA 1L trial, see the full prescribing information for brigatinib.

The approval of brigatinib was granted to ARIAD Pharmaceuticals. The approval of the Vysis ALK Break Apart FISH Probe Kit was granted to Abbott Molecular.

The Food and Drug Administration has approved dupilumab for children aged 6-11 years with moderate to severe atopic dermatitis, the manufacturers announced.

The new indication is for children “whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable,” Regeneron and Sanofi said in a press release, which points out that this is the first biologic approved for AD in this age group.

For children aged 6-11, the two available dupilumab (Dupixent) doses in prefilled syringes are given based on weight – 300 mg every 4 weeks for children between 15 to 29 kg and 200 mg every 2 weeks for children 30 to 59 kg – following an initial loading dose.

In phase 3 trials, children with severe AD who received dupilumab and topical corticosteroids improved significantly in overall disease severity, skin clearance, and itch, compared with those getting steroids alone. Eczema Area and Severity Index-75, for example, was reached by 75% of patients on either dupilumab dose, compared with 28% and 26% , respectively, for those receiving steroids alone every 4 and every 2 weeks, the statement said.

Over the 16-week treatment period, overall rates of adverse events were 65% for those getting dupilumab every 4 weeks and 61% for every 2 weeks – compared with steroids alone (72% and 75%, respectively), the statement said.

The fully human monoclonal antibody inhibits signaling of the interleukin-4 and interleukin-13 proteins and is already approved as an add-on maintenance treatment in children aged 12 years and older with moderate to severe asthma (eosinophilic phenotype or oral-corticosteroid dependent) and in adults with inadequately controlled chronic rhinosinusitis with nasal polyposis, according to the prescribing information.

[email protected]

The Food and Drug Administration has approved dupilumab for children aged 6-11 years with moderate to severe atopic dermatitis, the manufacturers announced.

The new indication is for children “whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable,” Regeneron and Sanofi said in a press release, which points out that this is the first biologic approved for AD in this age group.

For children aged 6-11, the two available dupilumab (Dupixent) doses in prefilled syringes are given based on weight – 300 mg every 4 weeks for children between 15 to 29 kg and 200 mg every 2 weeks for children 30 to 59 kg – following an initial loading dose.

In phase 3 trials, children with severe AD who received dupilumab and topical corticosteroids improved significantly in overall disease severity, skin clearance, and itch, compared with those getting steroids alone. Eczema Area and Severity Index-75, for example, was reached by 75% of patients on either dupilumab dose, compared with 28% and 26% , respectively, for those receiving steroids alone every 4 and every 2 weeks, the statement said.

Over the 16-week treatment period, overall rates of adverse events were 65% for those getting dupilumab every 4 weeks and 61% for every 2 weeks – compared with steroids alone (72% and 75%, respectively), the statement said.

The fully human monoclonal antibody inhibits signaling of the interleukin-4 and interleukin-13 proteins and is already approved as an add-on maintenance treatment in children aged 12 years and older with moderate to severe asthma (eosinophilic phenotype or oral-corticosteroid dependent) and in adults with inadequately controlled chronic rhinosinusitis with nasal polyposis, according to the prescribing information.

[email protected]

The Food and Drug Administration has approved dupilumab for children aged 6-11 years with moderate to severe atopic dermatitis, the manufacturers announced.

The new indication is for children “whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable,” Regeneron and Sanofi said in a press release, which points out that this is the first biologic approved for AD in this age group.

For children aged 6-11, the two available dupilumab (Dupixent) doses in prefilled syringes are given based on weight – 300 mg every 4 weeks for children between 15 to 29 kg and 200 mg every 2 weeks for children 30 to 59 kg – following an initial loading dose.

In phase 3 trials, children with severe AD who received dupilumab and topical corticosteroids improved significantly in overall disease severity, skin clearance, and itch, compared with those getting steroids alone. Eczema Area and Severity Index-75, for example, was reached by 75% of patients on either dupilumab dose, compared with 28% and 26% , respectively, for those receiving steroids alone every 4 and every 2 weeks, the statement said.

Over the 16-week treatment period, overall rates of adverse events were 65% for those getting dupilumab every 4 weeks and 61% for every 2 weeks – compared with steroids alone (72% and 75%, respectively), the statement said.

The fully human monoclonal antibody inhibits signaling of the interleukin-4 and interleukin-13 proteins and is already approved as an add-on maintenance treatment in children aged 12 years and older with moderate to severe asthma (eosinophilic phenotype or oral-corticosteroid dependent) and in adults with inadequately controlled chronic rhinosinusitis with nasal polyposis, according to the prescribing information.

[email protected]

Health care providers fail to ask one in five prenatal patients and one in eight postpartum patients about depression, according to the Centers for Disease Control and Prevention. Although the prevalence of screening has risen in recent years, many women could be suffering in silence.

“[U]ndetected and untreated perinatal depression can have negative health consequences for the mothers and their babies,” said coauthor Jean Y. Ko, PhD, from the division of reproductive health at the National Center for Chronic Disease Prevention and Health Promotion.

Dr. Ko and colleagues reported their findings in an article published in Morbidity and Mortality Weekly Report.

The researchers analyzed self-reported data on postpartum depressive symptoms (PDS) collected in 2018 by the Pregnancy Risk Assessment Monitoring System (PRAMS). Participants were stratified on the basis of location and maternal and infant characteristics, including age, race/ethnicity, and education level. Women who had recently given birth to one or more live infants answered questions about whether they had been screened by health care providers for depression during perinatal visits.

The prevalence of PDS among women from 31 PRAMS sites was 13.2%. States with lower prevalences included Illinois (9.7%), Massachusetts (10.3%), and Wisconsin (10.5%); states with higher prevalences included Mississippi (23.5%), West Virginia (19.4%), and Michigan (16.4%).

Some groups were at higher risk for PDS than others. The prevalence was greater than 20% among women who were aged 19 years or younger, were of American Indian or Alaska Native ethnicity, smoked during the perinatal period, experienced perinatal depression, or whose infant died after birth.

Depressive symptoms were also more common among women who received assistance from the Women, Infants, and Children program; were Medicaid beneficiaries at the time of delivery; smoked cigarettes during the last trimester of pregnancy; breastfed their infants for fewer than 8 weeks; or had experienced intimate partner violence while pregnant or before.
 

Small rise in screening

Overall, 79.1% of women said a health care provider had inquired about depression during the prenatal period. Prenatal screening for depression was lowest in Puerto Rico (50.7%), Mississippi (69.4%), Utah (69.5%), and Kentucky (69.5%) and was highest in Alaska (90.7%), Minnesota (90.6%), and Maine (90.5%).

Among 22 continuously reporting sites, the prevalence of prenatal depression screening rose significantly from 76.2% in 2016 to 79.3% in 2018 (P < .05) .

“It is unclear what might account for this small increase,” Dr. Ko said. “There may be additional factors, such as women may be becoming more comfortable reporting symptoms of depression. With continued awareness about the need to screen every pregnant and postpartum woman for depression, we can expect things to continue to improve.”

Overall, 90.1% of respondents reported a postpartum visit; of those, 87.4% said a health care provider had asked about depression during that visit.

Screening during the postpartum period was highest in Vermont (96.2%), Minnesota (95.9%), and Maine (95.5%) and was lowest in Puerto Rico (50.7%), New York City (73.1%), and Louisiana (75.0%).

Among the 22 sites that reported continuously, the prevalence of screening for postpartum depression rose significantly from 84.1% to 88.0% (P < .05), “with an average annual percentage point increase of 1.8%,” the authors wrote.
 

‘Missed opportunities’

“PRAMS responses are reported an average of 4 months postpartum, which suggests persistence of [depressive] symptoms,” the authors wrote.

Dr. Ko said that mental health conditions play a role in approximately 9% of pregnancy-related deaths and that not asking about depression represents “missed opportunities to potentially identify and treat women with depression.” The United States Preventive Services Task Force recommends screening all adults for depression, including women during pregnancy and the postpartum period, she added.

When asked what can be done to improve screening that has not already been tried, Dr. Ko said the CDC is currently evaluating a study called the Program in Support of Moms (PRISM), which “is designed to help obstetrics and gynecology practices address the significant public health issue of depression during and after pregnancy. PRISM aims to close gaps in health care delivery to ensure that women with depression during and after pregnancy receive the best treatment, which can result in improvement in their symptoms.”

Dr. Ko added that the Health Resources and Services Administration has funded seven states to begin “programs to support providers to screen, assess, refer, and treat pregnant and postpartum women for depression and other behavioral health conditions. States can use initiatives like Healthy Start, home visiting, and Title V Maternal and Child Health Services Block Grant programs as levers to improve screening and address maternal depression.

“Screening is just one part of addressing perinatal depression. Health care providers need to refer women to appropriate resources in order to get the proper diagnosis, treatment, and follow-up care for management of depression,” Dr. Ko concluded.

The authors disclosed no relevant financial relationships.

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

Health care providers fail to ask one in five prenatal patients and one in eight postpartum patients about depression, according to the Centers for Disease Control and Prevention. Although the prevalence of screening has risen in recent years, many women could be suffering in silence.

“[U]ndetected and untreated perinatal depression can have negative health consequences for the mothers and their babies,” said coauthor Jean Y. Ko, PhD, from the division of reproductive health at the National Center for Chronic Disease Prevention and Health Promotion.

Dr. Ko and colleagues reported their findings in an article published in Morbidity and Mortality Weekly Report.

The researchers analyzed self-reported data on postpartum depressive symptoms (PDS) collected in 2018 by the Pregnancy Risk Assessment Monitoring System (PRAMS). Participants were stratified on the basis of location and maternal and infant characteristics, including age, race/ethnicity, and education level. Women who had recently given birth to one or more live infants answered questions about whether they had been screened by health care providers for depression during perinatal visits.

The prevalence of PDS among women from 31 PRAMS sites was 13.2%. States with lower prevalences included Illinois (9.7%), Massachusetts (10.3%), and Wisconsin (10.5%); states with higher prevalences included Mississippi (23.5%), West Virginia (19.4%), and Michigan (16.4%).

Some groups were at higher risk for PDS than others. The prevalence was greater than 20% among women who were aged 19 years or younger, were of American Indian or Alaska Native ethnicity, smoked during the perinatal period, experienced perinatal depression, or whose infant died after birth.

Depressive symptoms were also more common among women who received assistance from the Women, Infants, and Children program; were Medicaid beneficiaries at the time of delivery; smoked cigarettes during the last trimester of pregnancy; breastfed their infants for fewer than 8 weeks; or had experienced intimate partner violence while pregnant or before.
 

Small rise in screening

Overall, 79.1% of women said a health care provider had inquired about depression during the prenatal period. Prenatal screening for depression was lowest in Puerto Rico (50.7%), Mississippi (69.4%), Utah (69.5%), and Kentucky (69.5%) and was highest in Alaska (90.7%), Minnesota (90.6%), and Maine (90.5%).

Among 22 continuously reporting sites, the prevalence of prenatal depression screening rose significantly from 76.2% in 2016 to 79.3% in 2018 (P < .05) .

“It is unclear what might account for this small increase,” Dr. Ko said. “There may be additional factors, such as women may be becoming more comfortable reporting symptoms of depression. With continued awareness about the need to screen every pregnant and postpartum woman for depression, we can expect things to continue to improve.”

Overall, 90.1% of respondents reported a postpartum visit; of those, 87.4% said a health care provider had asked about depression during that visit.

Screening during the postpartum period was highest in Vermont (96.2%), Minnesota (95.9%), and Maine (95.5%) and was lowest in Puerto Rico (50.7%), New York City (73.1%), and Louisiana (75.0%).

Among the 22 sites that reported continuously, the prevalence of screening for postpartum depression rose significantly from 84.1% to 88.0% (P < .05), “with an average annual percentage point increase of 1.8%,” the authors wrote.
 

‘Missed opportunities’

“PRAMS responses are reported an average of 4 months postpartum, which suggests persistence of [depressive] symptoms,” the authors wrote.

Dr. Ko said that mental health conditions play a role in approximately 9% of pregnancy-related deaths and that not asking about depression represents “missed opportunities to potentially identify and treat women with depression.” The United States Preventive Services Task Force recommends screening all adults for depression, including women during pregnancy and the postpartum period, she added.

When asked what can be done to improve screening that has not already been tried, Dr. Ko said the CDC is currently evaluating a study called the Program in Support of Moms (PRISM), which “is designed to help obstetrics and gynecology practices address the significant public health issue of depression during and after pregnancy. PRISM aims to close gaps in health care delivery to ensure that women with depression during and after pregnancy receive the best treatment, which can result in improvement in their symptoms.”

Dr. Ko added that the Health Resources and Services Administration has funded seven states to begin “programs to support providers to screen, assess, refer, and treat pregnant and postpartum women for depression and other behavioral health conditions. States can use initiatives like Healthy Start, home visiting, and Title V Maternal and Child Health Services Block Grant programs as levers to improve screening and address maternal depression.

“Screening is just one part of addressing perinatal depression. Health care providers need to refer women to appropriate resources in order to get the proper diagnosis, treatment, and follow-up care for management of depression,” Dr. Ko concluded.

The authors disclosed no relevant financial relationships.

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

Health care providers fail to ask one in five prenatal patients and one in eight postpartum patients about depression, according to the Centers for Disease Control and Prevention. Although the prevalence of screening has risen in recent years, many women could be suffering in silence.

“[U]ndetected and untreated perinatal depression can have negative health consequences for the mothers and their babies,” said coauthor Jean Y. Ko, PhD, from the division of reproductive health at the National Center for Chronic Disease Prevention and Health Promotion.

Dr. Ko and colleagues reported their findings in an article published in Morbidity and Mortality Weekly Report.

The researchers analyzed self-reported data on postpartum depressive symptoms (PDS) collected in 2018 by the Pregnancy Risk Assessment Monitoring System (PRAMS). Participants were stratified on the basis of location and maternal and infant characteristics, including age, race/ethnicity, and education level. Women who had recently given birth to one or more live infants answered questions about whether they had been screened by health care providers for depression during perinatal visits.

The prevalence of PDS among women from 31 PRAMS sites was 13.2%. States with lower prevalences included Illinois (9.7%), Massachusetts (10.3%), and Wisconsin (10.5%); states with higher prevalences included Mississippi (23.5%), West Virginia (19.4%), and Michigan (16.4%).

Some groups were at higher risk for PDS than others. The prevalence was greater than 20% among women who were aged 19 years or younger, were of American Indian or Alaska Native ethnicity, smoked during the perinatal period, experienced perinatal depression, or whose infant died after birth.

Depressive symptoms were also more common among women who received assistance from the Women, Infants, and Children program; were Medicaid beneficiaries at the time of delivery; smoked cigarettes during the last trimester of pregnancy; breastfed their infants for fewer than 8 weeks; or had experienced intimate partner violence while pregnant or before.
 

Small rise in screening

Overall, 79.1% of women said a health care provider had inquired about depression during the prenatal period. Prenatal screening for depression was lowest in Puerto Rico (50.7%), Mississippi (69.4%), Utah (69.5%), and Kentucky (69.5%) and was highest in Alaska (90.7%), Minnesota (90.6%), and Maine (90.5%).

Among 22 continuously reporting sites, the prevalence of prenatal depression screening rose significantly from 76.2% in 2016 to 79.3% in 2018 (P < .05) .

“It is unclear what might account for this small increase,” Dr. Ko said. “There may be additional factors, such as women may be becoming more comfortable reporting symptoms of depression. With continued awareness about the need to screen every pregnant and postpartum woman for depression, we can expect things to continue to improve.”

Overall, 90.1% of respondents reported a postpartum visit; of those, 87.4% said a health care provider had asked about depression during that visit.

Screening during the postpartum period was highest in Vermont (96.2%), Minnesota (95.9%), and Maine (95.5%) and was lowest in Puerto Rico (50.7%), New York City (73.1%), and Louisiana (75.0%).

Among the 22 sites that reported continuously, the prevalence of screening for postpartum depression rose significantly from 84.1% to 88.0% (P < .05), “with an average annual percentage point increase of 1.8%,” the authors wrote.
 

‘Missed opportunities’

“PRAMS responses are reported an average of 4 months postpartum, which suggests persistence of [depressive] symptoms,” the authors wrote.

Dr. Ko said that mental health conditions play a role in approximately 9% of pregnancy-related deaths and that not asking about depression represents “missed opportunities to potentially identify and treat women with depression.” The United States Preventive Services Task Force recommends screening all adults for depression, including women during pregnancy and the postpartum period, she added.

When asked what can be done to improve screening that has not already been tried, Dr. Ko said the CDC is currently evaluating a study called the Program in Support of Moms (PRISM), which “is designed to help obstetrics and gynecology practices address the significant public health issue of depression during and after pregnancy. PRISM aims to close gaps in health care delivery to ensure that women with depression during and after pregnancy receive the best treatment, which can result in improvement in their symptoms.”

Dr. Ko added that the Health Resources and Services Administration has funded seven states to begin “programs to support providers to screen, assess, refer, and treat pregnant and postpartum women for depression and other behavioral health conditions. States can use initiatives like Healthy Start, home visiting, and Title V Maternal and Child Health Services Block Grant programs as levers to improve screening and address maternal depression.

“Screening is just one part of addressing perinatal depression. Health care providers need to refer women to appropriate resources in order to get the proper diagnosis, treatment, and follow-up care for management of depression,” Dr. Ko concluded.

The authors disclosed no relevant financial relationships.

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

The Food and Drug Administration approved olaparib (Lynparza, AstraZeneca) for deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

The drug is limited to use in men who have progressed following prior treatment with enzalutamide or abiraterone.

Olaparib becomes the second PARP inhibitor approved by the FDA for use in prostate cancer this week. Earlier, rucaparib (Rubraca, Clovis Oncology) was approved for use in patients with mCRPC that harbor deleterious BRCA mutations (germline and/or somatic).

Olaparib is also indicated for use in ovarian, breast, and pancreatic cancers.

The FDA also approved two companion diagnostic devices for treatment with olaparib: the FoundationOne CDx test (Foundation Medicine) for the selection of patients carrying HRR gene alterations and the BRACAnalysis CDx test (Myriad Genetic Laboratories) for the selection of patients carrying germline BRCA1/2 alterations.

The approval was based on results from the open-label, multicenter PROfound trial, which randomly assigned 387 patients to olaparib 300 mg twice daily and to investigator’s choice of enzalutamide or abiraterone acetate. All patients received a GnRH analogue or had prior bilateral orchiectomy.

The study involved two cohorts. Patients with mutations in either BRCA1, BRCA2, or ATM were randomly assigned in cohort A (n = 245); patients with mutations among 12 other genes involved in the HRR pathway were randomly assigned in cohort B (n = 142); those with co-mutations were assigned to cohort A.

The major efficacy outcome of the trial was radiological progression-free survival (rPFS) (cohort A).

In cohort A, patients receiving olaparib had a median rPFS of 7.4 months vs 3.6 months among patients receiving investigator’s choice (hazard ratio [HR], 0.34; P < .0001). Median overall survival was 19.1 months vs 14.7 months (HR, 0.69; P = .0175) and the overall response rate was 33% vs 2% (P < .0001).

In cohort A+B, patients receiving olaparib had a median rPFS of 5.8 months vs 3.5 months among patients receiving investigator’s choice (HR, 0.49; P < .0001).

The study results were first presented at the 2019 annual meeting of the European Society for Medical Oncology. At that time, study investigator Maha Hussain, MD, Northwestern University, Chicago, said the rPFS result and other outcomes were a “remarkable achievement” in such heavily pretreated patients with prostate cancer.

Patients with prostate cancer should now undergo genetic testing of tumor tissue to identify the roughly 30% of patients who can benefit – as is already routinely being done for breast, ovarian, and lung cancer, said experts at ESMO.

The most common adverse reactions with olaparib (≥10% of patients) were anemia, nausea, fatigue (including asthenia), decreased appetite, diarrhea, vomiting, thrombocytopenia, cough, and dyspnea. Venous thromboembolic events, including pulmonary embolism, occurred in 7% of patients randomly assigned to olaparib, compared with 3.1% of those receiving investigator’s choice of enzalutamide or abiraterone.

Olaparib carries the warning that myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) occurred in <1.5% of patients exposed to it as a monotherapy, and that the majority of events had a fatal outcome.

The recommended olaparib dose is 300 mg taken orally twice daily, with or without food.

This article first appeared on Medscape.com.

The Food and Drug Administration approved olaparib (Lynparza, AstraZeneca) for deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

The drug is limited to use in men who have progressed following prior treatment with enzalutamide or abiraterone.

Olaparib becomes the second PARP inhibitor approved by the FDA for use in prostate cancer this week. Earlier, rucaparib (Rubraca, Clovis Oncology) was approved for use in patients with mCRPC that harbor deleterious BRCA mutations (germline and/or somatic).

Olaparib is also indicated for use in ovarian, breast, and pancreatic cancers.

The FDA also approved two companion diagnostic devices for treatment with olaparib: the FoundationOne CDx test (Foundation Medicine) for the selection of patients carrying HRR gene alterations and the BRACAnalysis CDx test (Myriad Genetic Laboratories) for the selection of patients carrying germline BRCA1/2 alterations.

The approval was based on results from the open-label, multicenter PROfound trial, which randomly assigned 387 patients to olaparib 300 mg twice daily and to investigator’s choice of enzalutamide or abiraterone acetate. All patients received a GnRH analogue or had prior bilateral orchiectomy.

The study involved two cohorts. Patients with mutations in either BRCA1, BRCA2, or ATM were randomly assigned in cohort A (n = 245); patients with mutations among 12 other genes involved in the HRR pathway were randomly assigned in cohort B (n = 142); those with co-mutations were assigned to cohort A.

The major efficacy outcome of the trial was radiological progression-free survival (rPFS) (cohort A).

In cohort A, patients receiving olaparib had a median rPFS of 7.4 months vs 3.6 months among patients receiving investigator’s choice (hazard ratio [HR], 0.34; P < .0001). Median overall survival was 19.1 months vs 14.7 months (HR, 0.69; P = .0175) and the overall response rate was 33% vs 2% (P < .0001).

In cohort A+B, patients receiving olaparib had a median rPFS of 5.8 months vs 3.5 months among patients receiving investigator’s choice (HR, 0.49; P < .0001).

The study results were first presented at the 2019 annual meeting of the European Society for Medical Oncology. At that time, study investigator Maha Hussain, MD, Northwestern University, Chicago, said the rPFS result and other outcomes were a “remarkable achievement” in such heavily pretreated patients with prostate cancer.

Patients with prostate cancer should now undergo genetic testing of tumor tissue to identify the roughly 30% of patients who can benefit – as is already routinely being done for breast, ovarian, and lung cancer, said experts at ESMO.

The most common adverse reactions with olaparib (≥10% of patients) were anemia, nausea, fatigue (including asthenia), decreased appetite, diarrhea, vomiting, thrombocytopenia, cough, and dyspnea. Venous thromboembolic events, including pulmonary embolism, occurred in 7% of patients randomly assigned to olaparib, compared with 3.1% of those receiving investigator’s choice of enzalutamide or abiraterone.

Olaparib carries the warning that myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) occurred in <1.5% of patients exposed to it as a monotherapy, and that the majority of events had a fatal outcome.

The recommended olaparib dose is 300 mg taken orally twice daily, with or without food.

This article first appeared on Medscape.com.

The Food and Drug Administration approved olaparib (Lynparza, AstraZeneca) for deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

The drug is limited to use in men who have progressed following prior treatment with enzalutamide or abiraterone.

Olaparib becomes the second PARP inhibitor approved by the FDA for use in prostate cancer this week. Earlier, rucaparib (Rubraca, Clovis Oncology) was approved for use in patients with mCRPC that harbor deleterious BRCA mutations (germline and/or somatic).

Olaparib is also indicated for use in ovarian, breast, and pancreatic cancers.

The FDA also approved two companion diagnostic devices for treatment with olaparib: the FoundationOne CDx test (Foundation Medicine) for the selection of patients carrying HRR gene alterations and the BRACAnalysis CDx test (Myriad Genetic Laboratories) for the selection of patients carrying germline BRCA1/2 alterations.

The approval was based on results from the open-label, multicenter PROfound trial, which randomly assigned 387 patients to olaparib 300 mg twice daily and to investigator’s choice of enzalutamide or abiraterone acetate. All patients received a GnRH analogue or had prior bilateral orchiectomy.

The study involved two cohorts. Patients with mutations in either BRCA1, BRCA2, or ATM were randomly assigned in cohort A (n = 245); patients with mutations among 12 other genes involved in the HRR pathway were randomly assigned in cohort B (n = 142); those with co-mutations were assigned to cohort A.

The major efficacy outcome of the trial was radiological progression-free survival (rPFS) (cohort A).

In cohort A, patients receiving olaparib had a median rPFS of 7.4 months vs 3.6 months among patients receiving investigator’s choice (hazard ratio [HR], 0.34; P < .0001). Median overall survival was 19.1 months vs 14.7 months (HR, 0.69; P = .0175) and the overall response rate was 33% vs 2% (P < .0001).

In cohort A+B, patients receiving olaparib had a median rPFS of 5.8 months vs 3.5 months among patients receiving investigator’s choice (HR, 0.49; P < .0001).

The study results were first presented at the 2019 annual meeting of the European Society for Medical Oncology. At that time, study investigator Maha Hussain, MD, Northwestern University, Chicago, said the rPFS result and other outcomes were a “remarkable achievement” in such heavily pretreated patients with prostate cancer.

Patients with prostate cancer should now undergo genetic testing of tumor tissue to identify the roughly 30% of patients who can benefit – as is already routinely being done for breast, ovarian, and lung cancer, said experts at ESMO.

The most common adverse reactions with olaparib (≥10% of patients) were anemia, nausea, fatigue (including asthenia), decreased appetite, diarrhea, vomiting, thrombocytopenia, cough, and dyspnea. Venous thromboembolic events, including pulmonary embolism, occurred in 7% of patients randomly assigned to olaparib, compared with 3.1% of those receiving investigator’s choice of enzalutamide or abiraterone.

Olaparib carries the warning that myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) occurred in <1.5% of patients exposed to it as a monotherapy, and that the majority of events had a fatal outcome.

The recommended olaparib dose is 300 mg taken orally twice daily, with or without food.

This article first appeared on Medscape.com.

In 2019, the number of births in the United States dropped for the fifth consecutive year, as did the fertility rate, and birth rates for women under age 30 fell to record lows, according to the National Center for Health Statistics.

To be exact – at least as exact as is possible from these provisional data – there were 3,745,540 births in the United States last year. That’s down about 1% from 2018 and is the lowest number of births since 1985, Brady E. Hamilton, PhD, and associates at the NCHS said in a rapid release report.

As births go, so goes the general fertility rate. A 2% decrease from 2018 to 2019 left the fertility rate at its lowest point ever: 58.2 births per 1,000 women aged 15-44 years, compared with 59.1 per 1,000 in 2018, the investigators said, based on data from the National Vital Statistics System.

The total fertility rate – defined as “the number of births that a hypothetical group of 1,000 women would have over their lifetimes, based on the age-specific birth rate in a given year” – also reached a record low of 1,705 births per 1,000 women last year after falling 1% from 2018, they reported.

The falling birth rates did not include women over age 35. The birth rate among women aged 40-44 increased by 2% from 2018, as it reached 12.0 births per 1,000 in 2019. “The rate for this age group has risen almost continuously since 1985 by an average of 3% per year,” Dr. Hamilton and associates wrote.

The birth rate for women aged 30-34 years, 98.3 per 1,000, was down 1% from 2018 but was still the highest for any age category. Among younger women, rates all dropped to record lows: 16.6 (ages 15-19), 66.6 (ages 20-24), and 93.7 (ages 25-29), they said.

Preterm birth rates, on the other hand, rose for the fifth year in a row. The rate for 2019, 10.23% of all births, represents an increase of 2% over 2018 and is “the highest level reported in more than a decade,” the investigators noted.

[email protected]

In 2019, the number of births in the United States dropped for the fifth consecutive year, as did the fertility rate, and birth rates for women under age 30 fell to record lows, according to the National Center for Health Statistics.

To be exact – at least as exact as is possible from these provisional data – there were 3,745,540 births in the United States last year. That’s down about 1% from 2018 and is the lowest number of births since 1985, Brady E. Hamilton, PhD, and associates at the NCHS said in a rapid release report.

As births go, so goes the general fertility rate. A 2% decrease from 2018 to 2019 left the fertility rate at its lowest point ever: 58.2 births per 1,000 women aged 15-44 years, compared with 59.1 per 1,000 in 2018, the investigators said, based on data from the National Vital Statistics System.

The total fertility rate – defined as “the number of births that a hypothetical group of 1,000 women would have over their lifetimes, based on the age-specific birth rate in a given year” – also reached a record low of 1,705 births per 1,000 women last year after falling 1% from 2018, they reported.

The falling birth rates did not include women over age 35. The birth rate among women aged 40-44 increased by 2% from 2018, as it reached 12.0 births per 1,000 in 2019. “The rate for this age group has risen almost continuously since 1985 by an average of 3% per year,” Dr. Hamilton and associates wrote.

The birth rate for women aged 30-34 years, 98.3 per 1,000, was down 1% from 2018 but was still the highest for any age category. Among younger women, rates all dropped to record lows: 16.6 (ages 15-19), 66.6 (ages 20-24), and 93.7 (ages 25-29), they said.

Preterm birth rates, on the other hand, rose for the fifth year in a row. The rate for 2019, 10.23% of all births, represents an increase of 2% over 2018 and is “the highest level reported in more than a decade,” the investigators noted.

[email protected]

In 2019, the number of births in the United States dropped for the fifth consecutive year, as did the fertility rate, and birth rates for women under age 30 fell to record lows, according to the National Center for Health Statistics.

To be exact – at least as exact as is possible from these provisional data – there were 3,745,540 births in the United States last year. That’s down about 1% from 2018 and is the lowest number of births since 1985, Brady E. Hamilton, PhD, and associates at the NCHS said in a rapid release report.

As births go, so goes the general fertility rate. A 2% decrease from 2018 to 2019 left the fertility rate at its lowest point ever: 58.2 births per 1,000 women aged 15-44 years, compared with 59.1 per 1,000 in 2018, the investigators said, based on data from the National Vital Statistics System.

The total fertility rate – defined as “the number of births that a hypothetical group of 1,000 women would have over their lifetimes, based on the age-specific birth rate in a given year” – also reached a record low of 1,705 births per 1,000 women last year after falling 1% from 2018, they reported.

The falling birth rates did not include women over age 35. The birth rate among women aged 40-44 increased by 2% from 2018, as it reached 12.0 births per 1,000 in 2019. “The rate for this age group has risen almost continuously since 1985 by an average of 3% per year,” Dr. Hamilton and associates wrote.

The birth rate for women aged 30-34 years, 98.3 per 1,000, was down 1% from 2018 but was still the highest for any age category. Among younger women, rates all dropped to record lows: 16.6 (ages 15-19), 66.6 (ages 20-24), and 93.7 (ages 25-29), they said.

Preterm birth rates, on the other hand, rose for the fifth year in a row. The rate for 2019, 10.23% of all births, represents an increase of 2% over 2018 and is “the highest level reported in more than a decade,” the investigators noted.

[email protected]

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.

A completely new approach to the treatment of prostate cancer is now available to clinicians through the approval of the first PARP inhibitor for use in certain patients with this disease.

Rucaparib (Rubraca, Clovis Oncology) is the first PARP inhibitor approved for use in patients with metastatic castration-resistant prostate cancer (mCRPC) that harbors deleterious BRCA mutations (germline and/or somatic). The drug is indicated for use in patients who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy.

The drug is already marketed for use in ovarian cancer.

The new prostate cancer indication was granted an accelerated approval by the US Food and Drug Administration (FDA) on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial. A confirmatory phase 3 trial, TRITON3, is currently underway.

“Standard treatment options for men with mCRPC have been limited to androgen receptor–targeting therapies, taxane chemotherapy, radium-223, and sipuleucel-T,” said Wassim Abida, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, in a statement.

“Rucaparib is the first in a class of drugs to become newly available to patients with mCRPC who harbor a deleterious BRCA mutation,” said Abida, who is also the principal investigator of the TRITON2 study. “Given the level and duration of responses observed with rucaparib in men with mCRPC and these mutations, it represents an important and timely new treatment option for this patient population.”
 

Other indications, another PARP inhibitor

Rucaparib is already approved for the treatment of women with advanced BRCA mutation–positive ovarian cancer who have received two or more prior chemotherapies. It is also approved as maintenance treatment for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who demonstrate a complete or partial response to platinum-based chemotherapy, regardless of BRCA status.

Another PARP inhibitor, olaparib (Lynparza, AstraZeneca), is awaiting approval for use in prostate cancer in men with BRCA mutations. That pending approval is based on results from the phase 3 PROfound trial, which was hailed as a “landmark trial” when it was presented last year. The results showed a significant improved in disease-free progression. The company recently announced that there was also a significant improvement in overall survival.

Olaparib is already approved for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status and as first-line maintenance treatment in BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved for germline BRCA-mutated HER2-negative metastatic breast cancer previously treated with chemotherapy and for the maintenance treatment of germline BRCA-mutated advanced pancreatic cancer following first-line platinum-based chemotherapy.
 

Details of the TRITON2 study

The accelerated approval for use of rucaparib in BRCA prostate cancer was based on efficacy data from the multicenter, single-arm TRITON2 clinical trial. The cohort included 62 patients with a BRCA (germline and/or somatic) mutation and measurable disease; 115 patients with a BRCA (germline and/or somatic) mutation and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency (HRD)–positive mCRPC.

The major efficacy outcomes were objective response rate (ORR) and duration of response. Confirmed PSA response rate was also a prespecified endpoint. Data were assessed by independent radiologic review.

For the patients with measurable disease and a BRCA mutation, the ORR was 44%. The ORR was similar for patients with a germline BRCA mutation.

Median duration of response was not evaluable at data cutoff but ranged from 1.7 to 24+ months. Of the 27 patients with a confirmed objective response, 15 (56%) patients showed a response that lasted 6 months or longer.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%.

The safety evaluation was based on an analysis of the 209 patients with HRD-positive mCRPC and included 115 with deleterious BRCA mutations. The most common adverse events (≥20%; grade 1-4) in the patients with BRCA mutations were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).

Rucaparib has been associated with hematologic toxicity, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, MDS/AML was not observed in the TRITON2 study, regardless of HRD mutation.
 

Confirmation with TRITON3

A phase 3, randomized, open-label study, TRITON3, is currently underway and is expected to serve as the confirmatory study for the accelerated approval in mCRPC. TRITON3 is comparing rucaparib with physician’s choice of therapy in patients with mCRPC who have specific gene alterations, including BRCA and ATM alterations, and who have experienced disease progression after androgen receptor–directed therapy but have not yet received chemotherapy. The primary endpoint for TRITON3 is radiographic progression-free survival.

This article first appeared on Medscape.com.

A completely new approach to the treatment of prostate cancer is now available to clinicians through the approval of the first PARP inhibitor for use in certain patients with this disease.

Rucaparib (Rubraca, Clovis Oncology) is the first PARP inhibitor approved for use in patients with metastatic castration-resistant prostate cancer (mCRPC) that harbors deleterious BRCA mutations (germline and/or somatic). The drug is indicated for use in patients who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy.

The drug is already marketed for use in ovarian cancer.

The new prostate cancer indication was granted an accelerated approval by the US Food and Drug Administration (FDA) on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial. A confirmatory phase 3 trial, TRITON3, is currently underway.

“Standard treatment options for men with mCRPC have been limited to androgen receptor–targeting therapies, taxane chemotherapy, radium-223, and sipuleucel-T,” said Wassim Abida, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, in a statement.

“Rucaparib is the first in a class of drugs to become newly available to patients with mCRPC who harbor a deleterious BRCA mutation,” said Abida, who is also the principal investigator of the TRITON2 study. “Given the level and duration of responses observed with rucaparib in men with mCRPC and these mutations, it represents an important and timely new treatment option for this patient population.”
 

Other indications, another PARP inhibitor

Rucaparib is already approved for the treatment of women with advanced BRCA mutation–positive ovarian cancer who have received two or more prior chemotherapies. It is also approved as maintenance treatment for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who demonstrate a complete or partial response to platinum-based chemotherapy, regardless of BRCA status.

Another PARP inhibitor, olaparib (Lynparza, AstraZeneca), is awaiting approval for use in prostate cancer in men with BRCA mutations. That pending approval is based on results from the phase 3 PROfound trial, which was hailed as a “landmark trial” when it was presented last year. The results showed a significant improved in disease-free progression. The company recently announced that there was also a significant improvement in overall survival.

Olaparib is already approved for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status and as first-line maintenance treatment in BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved for germline BRCA-mutated HER2-negative metastatic breast cancer previously treated with chemotherapy and for the maintenance treatment of germline BRCA-mutated advanced pancreatic cancer following first-line platinum-based chemotherapy.
 

Details of the TRITON2 study

The accelerated approval for use of rucaparib in BRCA prostate cancer was based on efficacy data from the multicenter, single-arm TRITON2 clinical trial. The cohort included 62 patients with a BRCA (germline and/or somatic) mutation and measurable disease; 115 patients with a BRCA (germline and/or somatic) mutation and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency (HRD)–positive mCRPC.

The major efficacy outcomes were objective response rate (ORR) and duration of response. Confirmed PSA response rate was also a prespecified endpoint. Data were assessed by independent radiologic review.

For the patients with measurable disease and a BRCA mutation, the ORR was 44%. The ORR was similar for patients with a germline BRCA mutation.

Median duration of response was not evaluable at data cutoff but ranged from 1.7 to 24+ months. Of the 27 patients with a confirmed objective response, 15 (56%) patients showed a response that lasted 6 months or longer.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%.

The safety evaluation was based on an analysis of the 209 patients with HRD-positive mCRPC and included 115 with deleterious BRCA mutations. The most common adverse events (≥20%; grade 1-4) in the patients with BRCA mutations were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).

Rucaparib has been associated with hematologic toxicity, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, MDS/AML was not observed in the TRITON2 study, regardless of HRD mutation.
 

Confirmation with TRITON3

A phase 3, randomized, open-label study, TRITON3, is currently underway and is expected to serve as the confirmatory study for the accelerated approval in mCRPC. TRITON3 is comparing rucaparib with physician’s choice of therapy in patients with mCRPC who have specific gene alterations, including BRCA and ATM alterations, and who have experienced disease progression after androgen receptor–directed therapy but have not yet received chemotherapy. The primary endpoint for TRITON3 is radiographic progression-free survival.

This article first appeared on Medscape.com.

A completely new approach to the treatment of prostate cancer is now available to clinicians through the approval of the first PARP inhibitor for use in certain patients with this disease.

Rucaparib (Rubraca, Clovis Oncology) is the first PARP inhibitor approved for use in patients with metastatic castration-resistant prostate cancer (mCRPC) that harbors deleterious BRCA mutations (germline and/or somatic). The drug is indicated for use in patients who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy.

The drug is already marketed for use in ovarian cancer.

The new prostate cancer indication was granted an accelerated approval by the US Food and Drug Administration (FDA) on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial. A confirmatory phase 3 trial, TRITON3, is currently underway.

“Standard treatment options for men with mCRPC have been limited to androgen receptor–targeting therapies, taxane chemotherapy, radium-223, and sipuleucel-T,” said Wassim Abida, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, in a statement.

“Rucaparib is the first in a class of drugs to become newly available to patients with mCRPC who harbor a deleterious BRCA mutation,” said Abida, who is also the principal investigator of the TRITON2 study. “Given the level and duration of responses observed with rucaparib in men with mCRPC and these mutations, it represents an important and timely new treatment option for this patient population.”
 

Other indications, another PARP inhibitor

Rucaparib is already approved for the treatment of women with advanced BRCA mutation–positive ovarian cancer who have received two or more prior chemotherapies. It is also approved as maintenance treatment for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who demonstrate a complete or partial response to platinum-based chemotherapy, regardless of BRCA status.

Another PARP inhibitor, olaparib (Lynparza, AstraZeneca), is awaiting approval for use in prostate cancer in men with BRCA mutations. That pending approval is based on results from the phase 3 PROfound trial, which was hailed as a “landmark trial” when it was presented last year. The results showed a significant improved in disease-free progression. The company recently announced that there was also a significant improvement in overall survival.

Olaparib is already approved for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status and as first-line maintenance treatment in BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved for germline BRCA-mutated HER2-negative metastatic breast cancer previously treated with chemotherapy and for the maintenance treatment of germline BRCA-mutated advanced pancreatic cancer following first-line platinum-based chemotherapy.
 

Details of the TRITON2 study

The accelerated approval for use of rucaparib in BRCA prostate cancer was based on efficacy data from the multicenter, single-arm TRITON2 clinical trial. The cohort included 62 patients with a BRCA (germline and/or somatic) mutation and measurable disease; 115 patients with a BRCA (germline and/or somatic) mutation and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency (HRD)–positive mCRPC.

The major efficacy outcomes were objective response rate (ORR) and duration of response. Confirmed PSA response rate was also a prespecified endpoint. Data were assessed by independent radiologic review.

For the patients with measurable disease and a BRCA mutation, the ORR was 44%. The ORR was similar for patients with a germline BRCA mutation.

Median duration of response was not evaluable at data cutoff but ranged from 1.7 to 24+ months. Of the 27 patients with a confirmed objective response, 15 (56%) patients showed a response that lasted 6 months or longer.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%.

The safety evaluation was based on an analysis of the 209 patients with HRD-positive mCRPC and included 115 with deleterious BRCA mutations. The most common adverse events (≥20%; grade 1-4) in the patients with BRCA mutations were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).

Rucaparib has been associated with hematologic toxicity, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, MDS/AML was not observed in the TRITON2 study, regardless of HRD mutation.
 

Confirmation with TRITON3

A phase 3, randomized, open-label study, TRITON3, is currently underway and is expected to serve as the confirmatory study for the accelerated approval in mCRPC. TRITON3 is comparing rucaparib with physician’s choice of therapy in patients with mCRPC who have specific gene alterations, including BRCA and ATM alterations, and who have experienced disease progression after androgen receptor–directed therapy but have not yet received chemotherapy. The primary endpoint for TRITON3 is radiographic progression-free survival.

This article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved ripretinib (Qinlock, Deciphera Pharmaceuticals) tablets as the first-ever drug specifically approved as a fourth-line treatment for advanced gastrointestinal stromal tumors (GISTs).

A new kinase inhibitor, ripretinib is indicated for patients previously treated with three or more other kinase inhibitor therapies, including imatinib.

“Despite the progress that has been made over the past 20 years in developing treatments for GIST … some patients don’t respond to treatment and their tumors continue to progress. Today’s approval provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST,” said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

Dr. Pazdur explained that the FDA has previously approved four targeted therapies for GISTs – imatinib in 2002, sunitinib in 2006, regorafenib in 2013, and avapritinib in 2020.

The new approval of ripretinib is based on the results of a multicenter, randomized, double-blind, placebo-controlled clinical trial that enrolled 129 patients with advanced GISTs whose disease progressed despite prior treatment with the other targeted therapies.

In the trial, patients received ripretinib or placebo once a day in 28-day cycles, until disease progression, or intolerable toxicity.

Median progression-free survival was 6.3 months in the ripretinib arm versus 1 month in the placebo arm.

The most common side effects with ripretinib were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, and vomiting.

Ripretinib also can cause skin cancer, hypertension, and cardiac dysfunction manifested as ejection fraction decrease.

The FDA collaborated with the Australian Therapeutic Goods Administration and Health Canada on the review of this application as part of Project Orbis.

This article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved ripretinib (Qinlock, Deciphera Pharmaceuticals) tablets as the first-ever drug specifically approved as a fourth-line treatment for advanced gastrointestinal stromal tumors (GISTs).

A new kinase inhibitor, ripretinib is indicated for patients previously treated with three or more other kinase inhibitor therapies, including imatinib.

“Despite the progress that has been made over the past 20 years in developing treatments for GIST … some patients don’t respond to treatment and their tumors continue to progress. Today’s approval provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST,” said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

Dr. Pazdur explained that the FDA has previously approved four targeted therapies for GISTs – imatinib in 2002, sunitinib in 2006, regorafenib in 2013, and avapritinib in 2020.

The new approval of ripretinib is based on the results of a multicenter, randomized, double-blind, placebo-controlled clinical trial that enrolled 129 patients with advanced GISTs whose disease progressed despite prior treatment with the other targeted therapies.

In the trial, patients received ripretinib or placebo once a day in 28-day cycles, until disease progression, or intolerable toxicity.

Median progression-free survival was 6.3 months in the ripretinib arm versus 1 month in the placebo arm.

The most common side effects with ripretinib were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, and vomiting.

Ripretinib also can cause skin cancer, hypertension, and cardiac dysfunction manifested as ejection fraction decrease.

The FDA collaborated with the Australian Therapeutic Goods Administration and Health Canada on the review of this application as part of Project Orbis.

This article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved ripretinib (Qinlock, Deciphera Pharmaceuticals) tablets as the first-ever drug specifically approved as a fourth-line treatment for advanced gastrointestinal stromal tumors (GISTs).

A new kinase inhibitor, ripretinib is indicated for patients previously treated with three or more other kinase inhibitor therapies, including imatinib.

“Despite the progress that has been made over the past 20 years in developing treatments for GIST … some patients don’t respond to treatment and their tumors continue to progress. Today’s approval provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST,” said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

Dr. Pazdur explained that the FDA has previously approved four targeted therapies for GISTs – imatinib in 2002, sunitinib in 2006, regorafenib in 2013, and avapritinib in 2020.

The new approval of ripretinib is based on the results of a multicenter, randomized, double-blind, placebo-controlled clinical trial that enrolled 129 patients with advanced GISTs whose disease progressed despite prior treatment with the other targeted therapies.

In the trial, patients received ripretinib or placebo once a day in 28-day cycles, until disease progression, or intolerable toxicity.

Median progression-free survival was 6.3 months in the ripretinib arm versus 1 month in the placebo arm.

The most common side effects with ripretinib were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, and vomiting.

Ripretinib also can cause skin cancer, hypertension, and cardiac dysfunction manifested as ejection fraction decrease.

The FDA collaborated with the Australian Therapeutic Goods Administration and Health Canada on the review of this application as part of Project Orbis.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval to pomalidomide (Pomalyst, Bristol-Myers Squibb) for the treatment of AIDS-related Kaposi sarcoma that is resistant to highly active antiretroviral therapy (HAART) or that occurs in HIV-negative patients.

Pomalidomide is the only oral agent and first new treatment option for Kaposi sarcoma in more than 20 years, according to the company.

The drug, a thalidomide analogue, is already marketed for the treatment of multiple myeloma.

Pomalidomide has “shown positive results in Kaposi sarcoma patients, regardless of their HIV status,” said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch, National Cancer Institute, in a press statement.

The conditional approval is based on the 71% overall response rate observed in a phase 1/2 open-label, single-arm clinical trial that involved 28 patients, 18 of whom were HIV positive and 10 of whom were HIV negative.

Most of the responses were partial (57%; 16/28); 14% (4/28) were complete. Median duration of response was 12.1 months. Additionally, for half of the patients who showed a response, that response was maintained for more than 12 months.

Patients received 5 mg of pomalidomide once daily for 21 of 28-day cycles until disease progression or unacceptable toxicity occurred.

Permanent discontinuation because of an adverse reaction occurred in 11% (3/28) of patients.

Adverse reactions (≥20%) included maculopapular rash (71%), constipation (71%), fatigue (68%), nausea (36%), diarrhea (32%), cough (29%), dyspnea (29%), peripheral edema (29%), upper respiratory tract infection (29%), muscle spasms (25%), hypothyroidism (21%), dry skin (21%), and chills (21%).

Grade 3 or 4 adverse reactions included maculopapular rash (3.6%), diarrhea (3.6%), and peripheral edema (3.6%).

Grade 3 or 4 laboratory abnormalities (≥5%) that worsened from baseline included decreased absolute neutrophil count (50%), decreased phosphate level (25%), elevated glucose level (7%), and elevated creatine kinase level (7%).

As a thalidomide analogue, pomalidomide includes a boxed warning in the prescribing information; thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. Deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke can occur in patients treated with pomalidomide; thromboprophylaxis is recommended.

Pomalidomide is available only through a restricted distribution program, Pomalyst REMS.

This article first appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval to pomalidomide (Pomalyst, Bristol-Myers Squibb) for the treatment of AIDS-related Kaposi sarcoma that is resistant to highly active antiretroviral therapy (HAART) or that occurs in HIV-negative patients.

Pomalidomide is the only oral agent and first new treatment option for Kaposi sarcoma in more than 20 years, according to the company.

The drug, a thalidomide analogue, is already marketed for the treatment of multiple myeloma.

Pomalidomide has “shown positive results in Kaposi sarcoma patients, regardless of their HIV status,” said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch, National Cancer Institute, in a press statement.

The conditional approval is based on the 71% overall response rate observed in a phase 1/2 open-label, single-arm clinical trial that involved 28 patients, 18 of whom were HIV positive and 10 of whom were HIV negative.

Most of the responses were partial (57%; 16/28); 14% (4/28) were complete. Median duration of response was 12.1 months. Additionally, for half of the patients who showed a response, that response was maintained for more than 12 months.

Patients received 5 mg of pomalidomide once daily for 21 of 28-day cycles until disease progression or unacceptable toxicity occurred.

Permanent discontinuation because of an adverse reaction occurred in 11% (3/28) of patients.

Adverse reactions (≥20%) included maculopapular rash (71%), constipation (71%), fatigue (68%), nausea (36%), diarrhea (32%), cough (29%), dyspnea (29%), peripheral edema (29%), upper respiratory tract infection (29%), muscle spasms (25%), hypothyroidism (21%), dry skin (21%), and chills (21%).

Grade 3 or 4 adverse reactions included maculopapular rash (3.6%), diarrhea (3.6%), and peripheral edema (3.6%).

Grade 3 or 4 laboratory abnormalities (≥5%) that worsened from baseline included decreased absolute neutrophil count (50%), decreased phosphate level (25%), elevated glucose level (7%), and elevated creatine kinase level (7%).

As a thalidomide analogue, pomalidomide includes a boxed warning in the prescribing information; thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. Deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke can occur in patients treated with pomalidomide; thromboprophylaxis is recommended.

Pomalidomide is available only through a restricted distribution program, Pomalyst REMS.

This article first appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval to pomalidomide (Pomalyst, Bristol-Myers Squibb) for the treatment of AIDS-related Kaposi sarcoma that is resistant to highly active antiretroviral therapy (HAART) or that occurs in HIV-negative patients.

Pomalidomide is the only oral agent and first new treatment option for Kaposi sarcoma in more than 20 years, according to the company.

The drug, a thalidomide analogue, is already marketed for the treatment of multiple myeloma.

Pomalidomide has “shown positive results in Kaposi sarcoma patients, regardless of their HIV status,” said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch, National Cancer Institute, in a press statement.

The conditional approval is based on the 71% overall response rate observed in a phase 1/2 open-label, single-arm clinical trial that involved 28 patients, 18 of whom were HIV positive and 10 of whom were HIV negative.

Most of the responses were partial (57%; 16/28); 14% (4/28) were complete. Median duration of response was 12.1 months. Additionally, for half of the patients who showed a response, that response was maintained for more than 12 months.

Patients received 5 mg of pomalidomide once daily for 21 of 28-day cycles until disease progression or unacceptable toxicity occurred.

Permanent discontinuation because of an adverse reaction occurred in 11% (3/28) of patients.

Adverse reactions (≥20%) included maculopapular rash (71%), constipation (71%), fatigue (68%), nausea (36%), diarrhea (32%), cough (29%), dyspnea (29%), peripheral edema (29%), upper respiratory tract infection (29%), muscle spasms (25%), hypothyroidism (21%), dry skin (21%), and chills (21%).

Grade 3 or 4 adverse reactions included maculopapular rash (3.6%), diarrhea (3.6%), and peripheral edema (3.6%).

Grade 3 or 4 laboratory abnormalities (≥5%) that worsened from baseline included decreased absolute neutrophil count (50%), decreased phosphate level (25%), elevated glucose level (7%), and elevated creatine kinase level (7%).

As a thalidomide analogue, pomalidomide includes a boxed warning in the prescribing information; thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. Deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke can occur in patients treated with pomalidomide; thromboprophylaxis is recommended.

Pomalidomide is available only through a restricted distribution program, Pomalyst REMS.

This article first appeared on Medscape.com.