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Welcome to the D.I.S.C.O., FDA’s Drug Information Soundcast in Clinical Oncology, Burst Edition, brought to you by FDA’s Division of Drug Information in partnership with FDA’s Oncology Center of Excellence. Recently we have another update on two recent FDA cancer drug approvals.

On April 13, 2021, the FDA granted accelerated approval to sacituzumab govitecan (brand name Trodelvy) for patients with locally advanced or metastatic urothelial cancer who previously received a platinum-containing chemotherapy and either a programmed death receptor-1 or a programmed death-ligand 1 inhibitor.

Efficacy and safety were evaluated in TROPHY, a single-arm, multicenter trial that enrolled 112 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a platinum-containing chemotherapy and either a programmed death receptor-1 or programmed death-ligand 1 inhibitor. The main efficacy endpoints were objective response rate and duration of response, evaluated by independent review using RECIST 1.1 criteria. The confirmed objective response rate was 27.7% with 5.4% complete responses and 22.3% partial responses. The median duration of response was 7.2 months.

The most common adverse reactions reported in more than 25% of patients receiving sacituzumab govitecan were neutropenia, nausea, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, decreased appetite, rash, and abdominal pain.

This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 6 weeks ahead of the FDA goal date.

On April 16, 2021, the FDA approved nivolumab (brand name Opdivo) in combination with fluoropyrimidine- and platinum-containing chemotherapy for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

Efficacy was evaluated in CHECKMATE-649, a randomized, multicenter, open-label trial that enrolled 1,581 patients with previously untreated advanced or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma. Programmed death-ligand 1 combined positive score was determined centrally using the Agilent/Dako programmed death-ligand 1 IHC 28-8 pharmDx test. Patients received nivolumab in combination with chemotherapy or chemotherapy alone.

The main efficacy outcome measures, assessed in patients with programmed death-ligand 1 combined positive score of greater than or equal to 5, were progression-free survival assessed by blinded independent central review and overall survival. CHECKMATE-649 demonstrated a statistically significant improvement in progression-free survival and overall survival for patients with programmed death-ligand 1 combined positive score of greater than or equal to 5. Median overall survival was 14.4 months in the nivolumab plus chemotherapy arm vs. 11.1 months in the chemotherapy alone arm. Median progression-free survival was 7.7 months in the nivolumab plus chemotherapy arm versus 6 months in the chemotherapy alone arm.

As an additional efficacy outcome measure, a statistically significant improvement in overall survival was also demonstrated for all randomized patients irrespective of combined positive score, with a median overall survival of 13.8 months in the nivolumab plus chemotherapy arm vs. 11.6 months in the chemotherapy alone arm.

The most common adverse reactions observed in more than 20% of patients receiving nivolumab in combination with fluoropyrimidine- and platinum-containing chemotherapy were peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation, and musculoskeletal pain.

The review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. The application reviews are ongoing at the other regulatory agencies.

This review also used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application approximately 5 weeks ahead of the FDA goal date.

Full prescribing information for these approvals can be found on the web at Drugs@FDA Search.

Health care professionals should report serious adverse events to FDA’s MedWatch Reporting System at www.fda.gov/medwatch.

Follow the Division of Drug Information on Twitter @FDA_Drug_Info and the Oncology Center of Excellence @FDAOncology. Send your feedback via email to FDAOncology@fda.hhs.gov. Thanks for tuning in to the D.I.S.C.O. Burst Edition.