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FDA Approvals in Prostate Cancer and Esophageal Cancer, and Promising Breast Cancer Data

Gina Columbus
Published: Monday, Aug 05, 2019



Today-

FDA approvals in prostate cancer and esophageal cancer, and promising findings in three breast cancer studies.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has approved darolutamide, known by the trade name Nubeqa, for the treatment of patients with nonmetastatic castration-resistant prostate cancer.

The decision to approve the androgen receptor inhibitor is based on data from the phase III ARAMIS trial, in which darolutamide in combination with androgen deprivation therapy led to a 59% reduction in the risk of metastases or death compared with placebo/ADT in this patient population. The median metastasis-free survival was 40.4 months with the addition of darolutamide versus 18.4 months with placebo/ADT at a median follow-up of 17.9 months.

Results also showed that OS data were not yet mature at the time of final MFS analysis, but data also showed a trend toward improved survival. The 3-year rates of OS were 83% in the darolutamide arm versus 73% with placebo, which translated to a 29% reduction in the risk of death.

Updated findings also showed that darolutamide also maintained quality of life and led to a delay in time to pain progression.

The approval took place 3 months ahead of the agency's action date. Bayer, the developer of darolutamide, stated that it has also filed for approval for darolutamide in the European Union, Japan, and with other regulatory authorities.

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In esophageal cancer, the FDA has approved pembrolizumab for the treatment of patients with recurrent locally advanced or metastatic disease whose tumors express PD-L1, with a combined positive score of at least 10, as determined by an FDA-approved test, with disease progression after at least 1 prior line of therapy.

The approval is based on findings from the phase III KEYNOTE-181 and phase II KEYNOTE-180 trials, in which pembrolizumab led to an improvement in median overall survival compared with chemotherapy and elicited encouraging overall response rates in patients with PD-L1–positive esophageal cancer, respectively.

In the multicenter, randomized, open-label, active-controlled KEYNOTE-181 study, results showed that pembrolizumab led to a 23% reduction in the risk of death compared with chemotherapy in patients with esophageal squamous cell carcinoma, a 30% reduction in those with PD-L1–positive tumors with a CPS of at least 10, and an 11% reduction in the risk of death in all randomized patients.

Additional follow-up showed that there was an improvement in OS in patients with ESCC who also had PD-L1–positive tumors with a CPS of at least 10 with pembrolizumab versus chemotherapy.

In the nonrandomized KEYNOTE-180 trial, findings showed that in 35 patients with PD-L1–positive ESCC with a CPS of at least 10, the ORR was 20%.

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The combination of abemaciclib and fulvestrant demonstrated a statistically significant improvement in overall survival compared with fulvestrant alone in patients with hormone receptor—positive, HER2-negative advanced or metastatic breast cancer who were previously treated with endocrine therapy.

The results were from a definitive preplanned interim analysis of the phase III MONARCH 2 trial, which previously demonstrated a statistically significant improvement in progression-free survival in both pre/peri and postmenopausal women, which was the basis for the FDA’s approval of the combination regimen in September 2018.

There were no new safety signals observed in the updated MONARCH 2 analysis. Lilly stated that it plans to present the full findings at an upcoming medical meeting and also submit the data to regulatory authorities.

Abemaciclib is FDA approved for the treatment of patients with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor for postmenopausal women as initial endocrine-based therapy, in combination with fulvestrant for patients with disease progression following endocrine therapy, and as a single agent for those with disease progression after endocrine therapy and prior chemotherapy in the metastatic setting.

***********************************

Also in breast cancer, the addition of the CDK4/6 inhibitor ribociclib to fulvestrant significantly improved overall survival as a first- or second-line treatment for postmenopausal women with hormone receptor–positive/HER2-negative breast cancer, according to findings from a preplanned interim analysis of the phase III MONALEESA-3 study.

This is the second phase III trial in which a ribociclib regimen has led to a statistically significant OS benefit in women with HR+/HER2- breast cancer. Earlier data showed that adding ribociclib to endocrine therapy led to a 29% reduction in the risk of death in peri or premenopausal women with advanced breast cancer.

Findings from MONALEESA-3 will be presented at an upcoming medical meeting and submitted to global regulatory authorities. Novartis, the developer of ribociclib, also noted that no new safety signals emerged since the initial read out of progression-free survival and other data from the trial.

The FDA initially approved ribociclib in 2017 in combination with an aromatase inhibitor for postmenopausal women with HR+/HER2- advanced breast cancer. The indication was later expanded to include pre and perimenopausal women with the disease, and also for combined use with fulvestrant for postmenopausal women.

*********************************

The combination of pembrolizumab and chemotherapy led to a statistically significant improvement in pathological complete response rates versus placebo plus chemotherapy in the neoadjuvant phase of a neoadjuvant/adjuvant treatment regimen in patients with triple-negative breast cancer, meeting one of the dual primary endpoints of the phase III KEYNOTE-522 trial.

Results of the interim analysis showed that the improvement in pCR was observed in patients regardless of PD-L1 status. Based on a recommendation by an Independent Data Monitoring Committee, the study will continue without changes to evaluate event-free survival, which is the other dual primary endpoint as per the trial design.

The safety data were consistent with prior data of pembrolizumab and no new safety signals were identified. Full findings will be presented at an upcoming medical meeting.

Prior phase Ib findings of the KEYNOTE-173 trial showed that the combination of pembrolizumab and platinum/taxane chemotherapy in the neoadjuvant setting induced high rates of pCR in patients with locally advanced TNBC.

*********************************

This week, we sat down with Dr. David Hyman, of Memorial Sloan Kettering Cancer Center, to discuss an NTRK as an attractive target for therapy.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.
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Today-

FDA approvals in prostate cancer and esophageal cancer, and promising findings in three breast cancer studies.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has approved darolutamide, known by the trade name Nubeqa, for the treatment of patients with nonmetastatic castration-resistant prostate cancer.

The decision to approve the androgen receptor inhibitor is based on data from the phase III ARAMIS trial, in which darolutamide in combination with androgen deprivation therapy led to a 59% reduction in the risk of metastases or death compared with placebo/ADT in this patient population. The median metastasis-free survival was 40.4 months with the addition of darolutamide versus 18.4 months with placebo/ADT at a median follow-up of 17.9 months.

Results also showed that OS data were not yet mature at the time of final MFS analysis, but data also showed a trend toward improved survival. The 3-year rates of OS were 83% in the darolutamide arm versus 73% with placebo, which translated to a 29% reduction in the risk of death.

Updated findings also showed that darolutamide also maintained quality of life and led to a delay in time to pain progression.

The approval took place 3 months ahead of the agency's action date. Bayer, the developer of darolutamide, stated that it has also filed for approval for darolutamide in the European Union, Japan, and with other regulatory authorities.

***********************************

In esophageal cancer, the FDA has approved pembrolizumab for the treatment of patients with recurrent locally advanced or metastatic disease whose tumors express PD-L1, with a combined positive score of at least 10, as determined by an FDA-approved test, with disease progression after at least 1 prior line of therapy.

The approval is based on findings from the phase III KEYNOTE-181 and phase II KEYNOTE-180 trials, in which pembrolizumab led to an improvement in median overall survival compared with chemotherapy and elicited encouraging overall response rates in patients with PD-L1–positive esophageal cancer, respectively.

In the multicenter, randomized, open-label, active-controlled KEYNOTE-181 study, results showed that pembrolizumab led to a 23% reduction in the risk of death compared with chemotherapy in patients with esophageal squamous cell carcinoma, a 30% reduction in those with PD-L1–positive tumors with a CPS of at least 10, and an 11% reduction in the risk of death in all randomized patients.

Additional follow-up showed that there was an improvement in OS in patients with ESCC who also had PD-L1–positive tumors with a CPS of at least 10 with pembrolizumab versus chemotherapy.

In the nonrandomized KEYNOTE-180 trial, findings showed that in 35 patients with PD-L1–positive ESCC with a CPS of at least 10, the ORR was 20%.

***********************************

The combination of abemaciclib and fulvestrant demonstrated a statistically significant improvement in overall survival compared with fulvestrant alone in patients with hormone receptor—positive, HER2-negative advanced or metastatic breast cancer who were previously treated with endocrine therapy.

The results were from a definitive preplanned interim analysis of the phase III MONARCH 2 trial, which previously demonstrated a statistically significant improvement in progression-free survival in both pre/peri and postmenopausal women, which was the basis for the FDA’s approval of the combination regimen in September 2018.

There were no new safety signals observed in the updated MONARCH 2 analysis. Lilly stated that it plans to present the full findings at an upcoming medical meeting and also submit the data to regulatory authorities.

Abemaciclib is FDA approved for the treatment of patients with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor for postmenopausal women as initial endocrine-based therapy, in combination with fulvestrant for patients with disease progression following endocrine therapy, and as a single agent for those with disease progression after endocrine therapy and prior chemotherapy in the metastatic setting.

***********************************

Also in breast cancer, the addition of the CDK4/6 inhibitor ribociclib to fulvestrant significantly improved overall survival as a first- or second-line treatment for postmenopausal women with hormone receptor–positive/HER2-negative breast cancer, according to findings from a preplanned interim analysis of the phase III MONALEESA-3 study.

This is the second phase III trial in which a ribociclib regimen has led to a statistically significant OS benefit in women with HR+/HER2- breast cancer. Earlier data showed that adding ribociclib to endocrine therapy led to a 29% reduction in the risk of death in peri or premenopausal women with advanced breast cancer.

Findings from MONALEESA-3 will be presented at an upcoming medical meeting and submitted to global regulatory authorities. Novartis, the developer of ribociclib, also noted that no new safety signals emerged since the initial read out of progression-free survival and other data from the trial.

The FDA initially approved ribociclib in 2017 in combination with an aromatase inhibitor for postmenopausal women with HR+/HER2- advanced breast cancer. The indication was later expanded to include pre and perimenopausal women with the disease, and also for combined use with fulvestrant for postmenopausal women.

*********************************

The combination of pembrolizumab and chemotherapy led to a statistically significant improvement in pathological complete response rates versus placebo plus chemotherapy in the neoadjuvant phase of a neoadjuvant/adjuvant treatment regimen in patients with triple-negative breast cancer, meeting one of the dual primary endpoints of the phase III KEYNOTE-522 trial.

Results of the interim analysis showed that the improvement in pCR was observed in patients regardless of PD-L1 status. Based on a recommendation by an Independent Data Monitoring Committee, the study will continue without changes to evaluate event-free survival, which is the other dual primary endpoint as per the trial design.

The safety data were consistent with prior data of pembrolizumab and no new safety signals were identified. Full findings will be presented at an upcoming medical meeting.

Prior phase Ib findings of the KEYNOTE-173 trial showed that the combination of pembrolizumab and platinum/taxane chemotherapy in the neoadjuvant setting induced high rates of pCR in patients with locally advanced TNBC.

*********************************

This week, we sat down with Dr. David Hyman, of Memorial Sloan Kettering Cancer Center, to discuss an NTRK as an attractive target for therapy.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.
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