Opdivo’s failure to demonstrate efficacy in both PD-L1 ≥5% and PD-L1 ≥50% patients solidifies Keytruda’s leading position for first-line NSCLC.
By Dustin Phan, Analyst
17 October 2016
I am an analyst at Datamonitor Healthcare based in the San Diego – California office, where I am currently a member of...
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Phase III data released at the 2016 European Society for Medical Oncology (ESMO) Congress revealed that Opdivo (nivolumab; Bristol-Myers Squibb/Ono Pharmaceutical) not only failed to meet its primary endpoint of progression-free survival (PFS) in patients with PD-L1 expression ≥5%, but the drug was also unable to demonstrate a benefit in patients with expression of ≥50%. Patients in the CheckMate 026 study were randomized to receive either Opdivo monotherapy or a physician’s choice platinum-based chemotherapy doublet. Those treated with Opdivo demonstrated a median PFS of 4.2 months compared with 5.9 months in those treated with chemotherapy (p=0.2511). Although the difference in these two treatment arms was not statistically significant, the hazard ratio (HR=1.15) suggests that patients receiving Opdivo performed worse than those receiving chemotherapy. Furthermore, while the study was not powered to demonstrate Opdivo’s efficacy in patient subgroups, subsequent analysis of patients with PD-L1 expression ≥50% revealed similarly disappointing results. The median PFS for this patient group was not available, but the hazard ratio for PFS was 1.07, again suggesting that patients treated with chemotherapy performed slightly better than those treated with Opdivo.
In comparison, Merck & Co presented positive results from a Phase III trial testing Keytruda (pembrolizumab) in first-line non-small cell lung cancer (NSCLC) patients with PD-L1 expression ≥50% at the 2016 ESMO Congress. Results from the KEYNOTE-024 trial revealed that patients treated with Keytruda exhibited a median PFS of 10.3 months, while those treated with a physician’s choice platinum-based chemotherapy exhibited a median PFS of 6.0 months (HR=0.5; p<0.001). Furthermore, the overall survival rate at six months was 80.2% in the Keytruda arm versus 72.4% in the chemotherapy arm (HR=0.60; p=0.005).
These data solidly position Keytruda as the leading PD-1/PD-L1 inhibitor for first-line NSCLC. While the target patient population of Keytruda will be limited to patients with PD-L1 expression ≥50%, the lack of competing immunotherapies in this setting will allow the drug to gain unimpeded uptake for some time. Opdivo is still in development for first-line NSCLC patients via the CheckMate 227 trial, which is testing the drug in combination with Yervoy (ipilimumab; Bristol-Myers Squibb) or chemotherapy. Nonetheless, Keytruda’s approval as a monotherapy will allow it to remain an attractive option for patients unable to tolerate the toxicities resulting from the addition of Yervoy or chemotherapy to Opdivo. Although Opdivo holds an advantage in the second-line setting due to its first-to-market status and broad label, the approval of Keytruda in the first-line setting will likely impact usage of Opdivo in previously treated patients, as the sequential use of PD-1 inhibitors has yet to be extensively explored.
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