Publication date: May 24, 2022
The trials that led to the approval showed an overall response rate (ORR) of just 10. 9% in patients with previously treated advanced melanoma, but the toxicity was severe. (The drug was also later approved as first-line monotherapy in patients whose melanoma expresses high levels of PD-L1. 17) Grade 3 or 4 immune-related adverse events (AEs) occurred in 10% to 15% of patients who received ipilimumab, and more than 2% of study patients suffered treatment-related deaths. The first was the enthusiasm that physicians like Flaherty had for directing patients away from approved treatments and toward trials. Pembrolizumabs accelerated approval was based on a 26% ORR in 173 patients with melanoma in the phase 1 KEYNOTE-001 study (NCT01295827). The PFS rate at 12 months was 47. 7% in the co bination group vs 36. 0% in the monotherapy group. Median PFS was only 5. 3 months because tumors developed resistance to treatment through MAP kinase reactivation.