Kirsten B. Goldberg

FDA Approval Summary: Atezolizumab for the Treatment of Patients with Progressive Advanced Urothelial Carcinoma after Platinum‐Containing Chemotherapy

On May 18, 2016, the U.S. Food and Drug Administration approved atezolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum‐containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum‐containing chemotherapy. This article summarizes key review findings that supported this approval.

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non‐Small Cell Lung Cancer: First‐Line Therapy and Beyond

This FDA approval summary provides an update on approval of pembrolizumab for treatment of patients with metastatic non‐small cell lung cancer whose tumors express PD‐L1 as determined by an FDA‐approved test. The results of KEYNOTE‐010 and KEYNOTE‐024 trials are presented.

A 25-Year Experience of US Food and Drug Administration Accelerated Approval of Malignant Hematology and Oncology Drugs and Biologics: A Review

Importance Accelerated approval (AA) is a US Food and Drug Administration (FDA) expedited program intended to speed the approval of drugs and biologics that may demonstrate a meaningful advantage over available therapies for diseases that are serious or life-threatening. Observations This review describes all malignant hematology and oncology AAs from inception of the program on December 11, 1992, to May 31, 2017. During this period, the FDA granted AA to 64 malignant hematology and oncology products for 93 new indications. Of these AAs, 53 were for new molecular entities. Overall, the end point of response rate, including hematologic response rates, accounted for most AAs (81 [87%]), followed by time-to-event end points of progression-free survival or time to progression (8 [9%]) and disease-free survival or recurrence-free survival (4 [4%]). Single-arm trial designs provided the data for 67 (72%) of the initial AA indications. Of the 93 AAs, 51 (55%) have fulfilled their postmarketing requirement and verified benefit in a median of 3.4 years after their initial AA. Thirty-seven (40%) indications have not yet completed confirmatory trial(s) or verified benefit, and 5 indications receiving AA (5%) have been withdrawn from the market. Conclusions and Relevance The use of the AA program during the past 25 years has increased over time, and only a small portion of indications under the AA program fail to verify clinical benefit. For patients with serious or life-threatening oncologic diseases, AA brings products to the market years before confirmatory trials are typically completed.

FDA Approval Summary: Daratumumab for Treatment of Multiple Myeloma After One Prior Therapy

Multiple myeloma is mostly an incurable disease. The U.S. Food and Drug Administration (FDA) granted daratumumab accelerated approval in November 2015 as monotherapy for patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double refractory to a proteasome and an immunomodulatory agent. This article describes the FDA review of the strength of evidence for this application and its clinical implications for the multiple myeloma population.

FDA Drug Approval: Elotuzumab in Combination with Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma

On November 30, 2015, the FDA approved elotuzumab (Empliciti; Bristol-Myers Squibb) in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who received one to three prior therapies. FDA approval was based primarily on the results of a phase III, randomized, open-label, multicenter trial, CA204004, which evaluated elotuzumab in combination with lenalidomide and dexamethasone (E-Ld) compared with lenalidomide and dexamethasone (Ld) alone in patients with relapsed or refractory multiple myeloma. Coprimary endpoints were progression-free survival (PFS) and overall response rate (ORR). The key secondary endpoint was overall survival, but these data were not mature at the time of clinical database cutoff. The trial demonstrated a statistically significant improvement in PFS, with an estimated HR of 0.70 for E-Ld over Ld [95% confidence interval (CI), 0.57–0.85; P = 0.0004). Estimated median PFS was 19.4 months in the E-Ld arm and 14.9 months in the Ld arm. ORR was 75.8% in the E-Ld arm compared with 65.5% in the Ld arm. Serious adverse reactions were reported in 65% of patients in the E-Ld arm compared with 57% in the Ld arm. The FDA approved elotuzumab with the following warnings and precautions: infusion reactions, infections, second primary malignancies, hepatotoxicity, and interference with the determination of complete response. Clin Cancer Res; 23(22); 6759–63. ©2017 AACR.

FDA Approval Summary: Dabrafenib and Trametinib for the Treatment of Metastatic Non‐Small Cell Lung Cancers Harboring BRAF V600E Mutations

This article summarizes the FDA review of the efficacy supplement supporting approval of dabrafenib and trametinib administered concurrently for BRAF V600E‐mutant non‐small cell lung cancer.

FDA Benefit‐Risk Assessment of Osimertinib for the Treatment of Metastatic Non‐Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation

This article reviews the benefit‐risk assessment of osimertinib that led to approval of osimertinib for the treatment of patients with metastatic EGFR T790M mutation‐positive non‐small cell lung cancer whose disease had progressed after EGFR tyrosine kinase inhibitor therapy.

Benefit‐Risk Summary of Regorafenib for the Treatment of Patients with Advanced Hepatocellular Carcinoma That Has Progressed on Sorafenib

Regorafenib is the first drug approved by the FDA for the treatment of hepatocellular carcinoma that has progressed on sorafenib and is expected to become a standard of care for these patients. This article summarizes the FDAs review of the data submitted in the supplemental New Drug Application and the basis for approval of regorafenib for this new indication.

Accelerating Early Access to Immunotherapies for Advanced Urothelial Carcinoma

Within one year, five immunotherapies have been approved for the treatment of patients with locally advanced or metastatic urothelial cancer. The availability of these immunotherapies brings challenges to all stakeholders in the field. Additional research is needed to identify biomarkers that are predictive of individual patient response to different immunotherapies.

FDA Approval Summary: Lenalidomide as Maintenance Therapy After Autologous Stem Cell Transplant in Newly Diagnosed Multiple Myeloma

This article provides a summary of the U.S. Food and Drug Administration (FDA) review of the marketing application for lenalidomide as maintenance therapy for patients with newly diagnosed multiple myeloma after autologous hematopoietic stem cell transplantation.