FDA News

TOP - November 2019, Vol 12, No 4 - FDA Updates

FDA Approves Erleada for Metastatic Castration-Sensitive Prostate Cancer

On September 17, 2019, the FDA approved a new indication for apalu­tamide (Erleada; Janssen Biotech) for the treatment of patients with metastatic castration-sensitive prostate cancer (CSPC). Apalutamide was initially approved in 2018 for the treatment of nonmetastatic castration-­resistant prostate cancer. The FDA granted apalutamide priority review for the new indication.

This new indication was approved based on results of the TITAN study, a randomized, double-blind, placebo-controlled clinical trial of 1052 patients with metastatic CSPC. Patients were randomized to apalutamide or to placebo. In addition, all patients also received androgen-deprivation therapy (ADT).

At a prespecified interim analysis, the hazard ratio (HR) for overall survival (OS) was 0.67 (95% confidence interval [CI], 0.51-0.89; P = .005); a median OS was not reached in either arm. The ­radiographic progression-­free survival (PFS) was HR 0.48 (95% CI, 0.39-0.60; P <.0001). The median radiographic PFS was not reached in the apalutamide (plus ADT) arm versus 22.1 months in the placebo (plus ADT) arm.

The most common (≥10%) side effects with apalutamide were fatigue, arthralgia, rash, decreased appetite, fall, decreased weight, hypertension, hot flushes, diarrhea, and fracture.

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Keytruda plus Lenvima Regimen FDA Approved for Advanced Endometrial Carcinoma with No MSI-H or dMMR Tumors

On September 17, 2019, the FDA accelerated the approval of a new combination of pembrolizumab (Keytruda; Merck) plus lenvatinib (Lenvima; Eisai) for patients with advanced endometrial carcinoma that is not associated with microsatellite instability high (MSI-H) or mismatch repair–deficient (dMMR) tumors in patients whose disease progressed after systemic therapy and who are candidates for curative surgery or radiation. The FDA granted this application priority review and a breakthrough therapy designation.

The approval of this combination was based on Study 111/KEYNOTE-146, a single-arm, multicenter, open­label, multicohort clinical trial of 108 patients with metastatic endometrial carcinoma that had progressed after ≥1 systemic therapies. Patients received oral lenvatinib 20 mg daily plus intravenous pembrolizumab 200 mg every 3 weeks, until disease progression or unacceptable toxicity.

Of the 108 patients, 94 had non–MSI-H or non-dMMR tumors, 11 patients had MSI-H or dMMR tumors, and 3 patients had unknown MSI-H or dMMR status. Efficacy was measured by objective response rate (ORR) and duration of response.

In the 94 patients without MSI-H or dMMR tumors, the ORR was 38.3% (95% confidence interval, 29%-49%), including 10 (10.6%) complete responses and 26 (27.7%) partial responses. The median duration of response was not reached at the time of data cutoff, and 25 (69%) responders had responses lasting ≥6 months.

Side effects with this combination were similar to those previously seen with each treatment.

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FDA Approves Daratumumab Combination for First-Line Treatment of Transplant-Eligible Patients with Multiple Myeloma

On September 26, 2019, the FDA approved daratumumab (Darzalex; Janssen Biotech), in combination with bortezomib (Velcade), thalidomide (Thalomid), and dexamethasone, for first-line treatment of multiple myeloma in patients eligible for autologous stem-cell transplant (ASCT). In June 2019, the FDA approved the combination of daratumumab plus lenalidomide (Revlimid) and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for ASCT. The FDA granted this application a priority review.

This approval was based on an open-label, randomized, active-controlled phase 3 clinical trial that compared induction and consolidation treatments with daratumumab plus bortezomib, thalidomide, and dexamethasone (DVTd) versus bortezomib, thalidomide, and dexamethasone (VTd) alone in patients with newly diagnosed multiple myeloma who are eligible for ASCT.

The efficacy measures were pro­gression-free survival (PFS), stringent complete response at 100 days post-ASCT, and complete response rate at day 100 post-ASCT. At a median follow-up of 18.8 months, the median PFS had not been reached in either arm. However, DVTd reduced the risk for disease progression or death by 53% compared with VTd alone (hazard ratio, 0.47; 95% confidence interval, 0.33-0.67; P <.0001). At day 100 post-ASCT, the stringent complete responses were 28.9% with DVTd versus 20.3% with VTd alone.

The most common (≥20%) adverse events were infusion reactions, peripheral sensory neuropathy, constipation, asthenia, nausea, peripheral edema, neutropenia, thrombocytopenia, pyrexia, and paresthesia. There were no significant differences in the number or type of serious adverse events in the 2 arms.

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Last modified: July 22, 2021