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.
Semantics
| Type | Source | Name |
|---|---|---|
| drug | DRUGBANK | Atezolizumab |
| drug | DRUGBANK | Binimetinib |
| drug | DRUGBANK | Encorafenib |
| drug | DRUGBANK | Cobimetinib |
| drug | DRUGBANK | Trametinib |
| drug | DRUGBANK | Dabrafenib |
| disease | MESH | death |
| drug | DRUGBANK | Vemurafenib |
| drug | DRUGBANK | Talimogene laherparepvec |
| disease | MESH | brain metastases |
| disease | MESH | community |
| drug | DRUGBANK | Pembrolizumab |
| drug | DRUGBANK | Nivolumab |
| pathway | REACTOME | Immune System |
| drug | DRUGBANK | Ipilimumab |
| drug | DRUGBANK | Tropicamide |
| disease | MESH | Cancer |
| drug | DRUGBANK | Dacarbazine |
| pathway | KEGG | Melanoma |
| disease | MESH | Melanoma |