Welcome to the DISCO, 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. Today we have an update on two recent FDA cancer drug approvals.
On April 6, 2021, FDA approved a new dosage regimen of 500 mg/m² as a 120 minute intravenous infusion every two weeks for cetuximab (brand name Erbitux) for patients with K-Ras wild-type, EGFR-expressing colorectal cancer or squamous cell carcinoma of the head and neck.
This approval provides for a biweekly dosage regimen option in addition to the previously approved weekly dosage regimen for the approved indications when cetuximab is used as a single agent or in combination with chemotherapy.
The approval was based on population PK modeling analyses that compared the predicted exposures of cetuximab 500 mg every two weeks, to observed cetuximab exposures in patients who received 250 mg weekly. The application was also supported by pooled analyses of overall response rates, progression-free survival, and overall survival from published literature in patients with colorectal cancer and squamous cell carcinoma of the head and neck, and overall survival analyses using real-world data in patients with EGFR-expressing colorectal cancer who received either the weekly cetuximab or every two weeks regimen. In these exploratory analyses, the observed efficacy results were consistent across dosage regimens and supported the results of the population PK modeling analyses.
The most common adverse reactions to cetuximab, reported in more than 25% of patients were cutaneous adverse reactions (including rash, pruritus, and nail changes), headache, diarrhea, and infection.
The FDA approved this application approximately 5 months ahead of the FDA goal date.
On April 7, 2021, FDA approved sacituzumab govitecan (brand name Trodelvy) for patients with unresectable locally advanced or metastatic triple-negative breast cancer who have received two or more prior systemic therapies, at least one for metastatic disease.
Efficacy and safety were evaluated in ASCENT, a multicenter, open-label, randomized trial conducted in 529 patients with unresectable locally advanced or metastatic triple-negative breast cancer who had relapsed after at least two prior chemotherapies, one of which could be in the neoadjuvant or adjuvant setting if progression occurred within 12 months. Patients were randomized 1:1 to receive sacituzumab govitecan, or physician’s choice of single agent chemotherapy.
The primary efficacy endpoint was progression-free survival in patients without brain metastases at baseline as measured by a blinded, independent, centralized review assessed using RECIST 1.1 criteria. Additional efficacy endpoints included progression-free survival for the full population with and without brain metastases and overall survival.
Among all randomized patients, median progression-free survival for patients receiving sacituzumab govitecan was 4.8 months compared with 1.7 months in those receiving chemotherapy. Median overall survival was 11.8 months and 6.9 months respectively.
This trial was the confirmatory trial for the April 2020 accelerated approval for patients with metastatic triple-negative breast cancer.
Most common adverse reactions reported in more than 25% of patients receiving sacituzumab govitecan were nausea, neutropenia, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, rash, decreased appetite, and abdominal pain.
This 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 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 6 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 MedWatch: The FDA Safety Information and Adverse Event Reporting Program.
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 into this D.I.S.C.O. Burst Edition.