September 18, 2019 : Episode 1

FDA Approvals in Prostate Cancer and Endometrial Cancer, and Priority Review in Urothelial Cancer



FDA approvals in prostate cancer and endometrial cancer, a priority review designation in urothelial carcinoma, a warning issued by the FDA in breast cancer, and promising findings in a multiple myeloma trial.

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

The FDA has approved apalutamide for the treatment of patients with metastatic castration-sensitive prostate cancer.

The approval is based on data from the phase III TITAN study, which showed that apalutamide plus androgen deprivation therapy led to a 33% reduction in the risk of death versus placebo and ADT in this patient population.

At a median follow-up of 22.7 months, the 2-year overall survival rate was 82.4% with apalutamide versus 73.5% in patients receiving ADT alone. The median OS was not yet reached in either arm.

Moreover, the addition of apalutamide also reduced the risk of radiographic progression or death by 52%. The median radiographic progression-free survival was not reached in the apalutamide arm versus 22.1 months in the control arm. The 2-year rPFS rates were 68.2% versus 47.5%, respectively, and the OS and rPFS benefits were observed across patient subgroups.

Apalutamide was approved by the FDA for the treatment of patients with nonmetastatic castration-resistant prostate cancer in February 2018.


In endometrial cancer, the FDA has granted an accelerated approval to the combination of lenvatinib and pembrolizumab for the treatment of patients with advanced disease that is not microsatellite instability-high or mismatch repair deficient, and who have disease progression following prior systemic therapy but are ineligible for curative surgery or radiation.

The approval is based on data from 94 patients with endometrial carcinoma tumors that were not MSI-H or dMMR. Of these patients, the overall response rate was 38.3%, which included a 10.6% complete response rate and a partial response rate of 27.7%. A duration of response at 6 months or greater was reported in 69% of patients.

The decision is part of Project Orbis, which is a new initiative of the FDA Oncology Center of Excellence. Project Orbis is designed to provide a framework for concurrent submission and review of oncology drugs among international partners. Under this initiative, the FDA, the Australian Therapeutic Goods Administration, and Health Canada collaboratively reviewed applications for the two agents, and allowed for simultaneous approvals in all 3 countries.

In August, the FDA granted a breakthrough therapy designation to this combination in this patient population who have progressed after at least 1 prior systemic therapy.


In urothelial cancer, the FDA has granted a priority review designation to a biologics license application for enfortumab vedotin for the treatment of patients with locally advanced or metastatic disease who have received prior treatment with a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic setting.

The designation is based on results from the first cohort of patients in the phase II EV-201 trial, which showed that enfortumab vedotin elicited an overall response rate of 44% in patients with locally advanced or metastatic urothelial cancer, which included a 12% complete response rate.

The FDA must make a decision on the application by March 15, 2020.

Additional results of EV-201 showed that the overall survival was 11.7 months, the median progression-free survival was 5.8 months, and the median duration of response was 7.6 months.

Responses were observed across all subgroups, irrespective of response to prior PD-1/PD-L1 inhibitors or presence of liver metastases. The median time to response was 1.8 months, with 44% of responses ongoing.


The FDA is updating the prescribing information and Patient Package Insert for the CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib to include a warning that the treatments in rare cases may cause severe inflammation of the lungs.

Since the inflammation can be life-threatening, the FDA recommends that patients receiving CDK4/6 inhibitors should immediately contact their healthcare professional if they experience shortness of breath with low activity or while at rest, or discomfort or difficulty breathing.

The agency also warned that patients should not stop taking a CDK4/6 inhibitor without first consulting with their healthcare professional.

In their statement, the FDA also noted that the overall benefit of CDK4/6 inhibitors is still greater than the risks when used as prescribed.


In multiple myeloma, phase III data from the CANDOR trial showed that the addition of daratumumab to carfilzomib and dexamethasone—known as the DKd regimen—improved progression-free survival in patients with relapsed/refractory disease.

The topline findings showed that the DKd triplet reduced the risk of disease progression or death by 37% versus carfilzomib and dexamethasone alone. The median PFS was not yet reached with DKd compared with 15.8 months with Kd alone.

Moreover, no new safety signals emerged with the study drugs compared with historical data. Treatment-emergent adverse advents occurring in at least 20% of patients in the DKd arm included thrombocytopenia, anemia, diarrhea, hypertension, upper respiratory tract infection, fatigue, and dyspnea.

The CANDOR findings will be discussed with regulatory authorities and the full findings will be presented at an upcoming medical meeting.

Earlier phase Ib trial data showed that the daratumumab triplet elicited an overall response rate of 84%, including 79% in lenalidomide-refractory patients.


This week, we sat down with Dr Mark Kris, of Memorial Sloan Kettering Cancer, to discuss MET as a clinical target in lung cancer.

That’s all for today.

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

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