FDA approves enfortumab vedotin with pembrolizumab for advanced bladder cancer
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Key takeaways:
- The FDA approved a combination therapy for locally advanced or metastatic bladder cancer.
- The combination therapy improved OS and PFS compared with platinum-based chemotherapy in a phase 3 trial.
The FDA approved enfortumab vedotin-ejfv in combination with pembrolizumab for patients with locally advanced or metastatic urothelial cancer, according to an agency press release.
The FDA previously granted accelerated approval for the combination therapy (Padcev, Astellas Pharma, plus Keytruda, Merck) for patients with locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-containing chemotherapy.
As Healio previously reported, efficacy was evaluated in the phase 3 EV-302/KN-A39, an open-label, randomized trial of 886 patients with locally advanced or metastatic urothelial cancer and no prior systemic therapy for advanced disease. Researchers randomly assigned patients to receive either enfortumab vedotin-ejfv with pembrolizumab or platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin). Randomization was stratified by cisplatin eligibility, PD-L1 expression and presence of liver metastases.
Researchers observed improvements in both OS and PFS for enfortumab vedotin-ejfv with pembrolizumab compared with platinum-based chemotherapy. Median OS was 31.5 months (95% CI, 25.4, not estimable) for patients who received enfortumab vedotin-ejfv with pembrolizumab and 16.1 months (95% CI, 13.9-18.3) for those who received platinum-based chemotherapy, for an HR of 0.47 (95% CI, 0.38-0.58). Median PFS was 12.5 months (95% CI: 10.4-16.6) for patients who received enfortumab vedotin-ejfv with pembrolizumab and 6.3 months (95% CI, 6.2-6.5) for those who received platinum-based chemotherapy, for an HR of 0.45 (95% CI, 0.38-0.54).
The most common adverse reactions, including laboratory abnormalities, in patients receiving enfortumab vedotin-ejfv with pembrolizumab were increased aspartate aminotransferase, increased creatinine, rash, increased glucose, peripheral neuropathy, increased lipase, decreased lymphocytes, increased alanine aminotransferase, decreased hemoglobin, fatigue, decreased sodium, decreased phosphate, decreased albumin, pruritus, diarrhea, alopecia, decreased weight, decreased appetite, increased urate, decreased neutrophils, decreased potassium, dry eye, nausea, constipation, increased potassium, dysgeusia, urinary tract infection and decreased platelets.
The recommended enfortumab vedotin-ejfv dose when given with pembrolizumab is 1.25 mg/kg (up to a maximum of 125 mg for patients weight more than 100 kg) administered as an intravenous infusion over 30 minutes on days 1 and 8 of a 21-day cycle until disease progression or unacceptable toxicity.
The recommended pembrolizumab dose when given with enfortumab vedotin-ejfv is 200 mg administered as an IV infusion every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or 2 years of therapy.
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. For this review, FDA collaborated with the Australian Therapeutic Goods Administration and Health Canada.
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 5 months ahead of the FDA goal date.
This application was granted priority review and breakthrough designation.
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