Welcome back 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. Today we’ll provide another quick update on two recent FDA cancer drug approvals. On May 27, 2022, the FDA approved the following for the first-line treatment of patients with advanced or metastatic esophageal squamous cell carcinoma:
- nivolumab (brand name Opdivo) in combination with fluoropyrimidine- and platinum-based chemotherapy
- nivolumab in combination with ipilimumab (brand name Yervoy)
Efficacy was evaluated in CHECKMATE-648, a randomized, active-controlled, open-label trial in 970 patients with previously untreated unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma. Prior treatment with curative intent was allowed if completed more than six months before trial enrollment. The trial excluded patients with brain metastasis that were symptomatic, active autoimmune disease, receiving systemic corticosteroids or immunosuppressants, or patients at high risk of bleeding or fistula due to apparent invasion of tumor to organs adjacent to the esophageal tumor. The major efficacy outcome measures were overall survival and blinded independent central review-assessed progression-free survival. CHECKMATE-648 demonstrated statistically significant improvements in overall survival in all randomized patients and in the subpopulation with tumor cell PD-L1 greater than or equal to 1% for both nivolumab-containing regimens when individually compared to chemotherapy.
In the ITT population overall survival results revealed:
- The hazard ratio of the comparison nivolumab, fluorouracil, and cisplatin vs. chemotherapy was 0.74.
- The hazard ratio of the comparison of nivolumab and ipilimumab vs. chemotherapy was 0.78.
In the ITT population, the median overall survival was 13.2 months in the nivolumab, fluorouracil, and cisplatin arm, 12.8 months in the nivolumab and ipilimumab arm, and 10.7 months in the fluorouracil and cisplatin arm.
In the tumor cell PD-L1 greater than 1% population overall survival results revealed:
- The hazard ratio for the comparison nivolumab, fluorouracil, and cisplatin vs. chemotherapy alone was 0.54.
- The hazard ratio of the comparison of nivolumab and ipilimumab vs. chemotherapy was 0.64.
The most common adverse reactions occurring in more than 20% of patients treated with nivolumab and fluoropyrimidine- and platinum-containing chemotherapy in CHECKMATE-648 were nausea, decreased appetite, fatigue, constipation, stomatitis, diarrhea, and vomiting. The most common adverse reactions occurring in more than 20% of patients treated with nivolumab and ipilimumab in CHECKMATE-648 were rash, fatigue, pyrexia, nausea, diarrhea, and constipation.
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 application reviews may be ongoing at the other regulatory agencies.
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.
Also on May 27, 2022, the FDA granted accelerated approval to tisagenlecleucel (brand name Kymriah) for adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.
The approval was based on the ELARA trial, a multicenter, single-arm, open-label trial evaluating tisagenlecleucel, a CD19-directed chimeric antigen receptor T cell therapy, in adult patients who were refractory or relapsed within 6 months after completion of two or more lines of systemic therapy or relapsed after autologous hematopoietic stem cell transplant.
The main efficacy measures were overall response rate and duration of response as determined by an independent review committee. Among 90 patients in the primary efficacy analysis, the overall response rate was 86% with a complete response rate of 68%. The median duration of response was not reached, with 75% of responders still in response at 9 months. For all patients who underwent leukapheresis, the overall response rate was 86% with a complete response rate of 67%.
The most common adverse reactions occurring in more than 20% of patients were cytokine release syndrome, infection, fatigue, musculoskeletal pain, headache, and diarrhea.
This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 1 month ahead of the FDA goal date.
Full prescribing information for these approvals can be found at www.fda.gov/drugsatFDA.
Health care professionals should report serious adverse events to FDA’s MedWatch Reporting Program at www.fda.gov/medwatch.
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