FDA Approval Summary: Pembrolizumab for Neoadjuvant and Adjuvant Treatment of Patients with High-Risk Early-Stage Triple-Negative Breast Cancer.

On July 26, 2021, the FDA granted approval to pembrolizumab in combination with chemotherapy for neoadjuvant treatment and then continued as a single agent for adjuvant treatment following surgery for patients with high-risk, early-stage triple-negative breast cancer. Approval was based on results from KEYNOTE-522, an ongoing randomized (2:1) trial evaluating pembrolizumab or placebo in combination with chemotherapy for neoadjuvant treatment and then as a single agent for adjuvant treatment. The co-primary endpoints were pathological complete response (pCR) rate and event-free survival (EFS). The trial demonstrated an improvement in pCR and EFS in the pembrolizumab arm compared with the control arm. The number of patients who experienced an EFS event was 123 (16%) and 93 (24%), respectively [HR: 0.63, 95% confidence interval (CI), 0.48-0.82, P = 0.00031]. Patients on the pembrolizumab arm experienced EFS benefit regardless of tumor PD-L1 status. The absolute pCR rate improvement with the addition of pembrolizumab was 7.5% (95% CI, 1.6-13.4). Among patients receiving pembrolizumab, 44% experienced an immune-related adverse reaction. This article summarizes FDA's review of pembrolizumab and the data supporting the favorable benefit-risk assessment.

FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA Mutation-Associated Advanced Ovarian Cancer.

On December 19, 2016, the FDA granted accelerated approval to rucaparib (RUBRACA; Clovis Oncology, Inc.) for the treatment of patients with deleterious BRCA mutation (germline and/or somatic)-associated advanced ovarian cancer who have been treated with two or more chemotherapies. The FDA also approved the FoundationFocus CDx BRCA test (Foundation Medicine, Inc.), the first next-generation sequencing-based companion diagnostic, for identifying patients with advanced ovarian cancer eligible for treatment with rucaparib based on detection of deleterious BRCA1 and/or BRCA2 mutations in tumor tissue. Rucaparib's approval was based primarily on efficacy data from 106 patients with BRCA mutation-associated ovarian cancer who had prior treatment with two or more chemotherapies and safety data from 377 patients with ovarian cancer treated with rucaparib 600 mg orally twice daily on two open-label, single-arm trials. Investigator-assessed objective response rate was 54% [57/106; 95% confidence interval (CI), 44-64], and median duration of response was 9.2 months (95% CI, 6.6-11.7). The approved companion diagnostic verified tumor BRCA mutation status retrospectively in 96% (64/67) of patients. Common adverse reactions (≥20%) to rucaparib were nausea, fatigue, vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea. This article summarizes the FDA review and data supporting rucaparib's accelerated approval. Clin Cancer Res; 23(23); 7165-70. ©2017 AACRSee related commentary by Kohn et al., p. 7155.