The addition of ipilimumab (Yervoy®; Bristol Myers Squibb) to pembrolizumab (Keytruda®; Merck) did not improve overall survival (OS) or progression free survival (PFS) in patients with metastatic non-small cell lung cancer (NSCLC) without EGFR or ALK genomic tumor aberrations and whose tumors express PD-L1 (tumor proportion score [TPS] greater than or equal to 50%), according to findings from the KEYNOTE-598 study.
The randomized, double-blind trial (N=568) compared the efficacy and safety of pembrolizumab plus ipilimumab to pembrolizumab monotherapy for first-line treatment of metastatic NSCLC. Patients were randomly assigned 1:1 to receive pembrolizumab 200mg intravenously (IV) on day 1 of each 3-week cycle for up to 35 cycles plus ipilimumab 1mg/kg IV on day 1 of each 6-week cycle for up to 18 cycles or pembrolizumab monotherapy.
Results showed the median OS was 21.4 months in the pembrolizumab plus ipilimumab arm compared with 21.9 months in the pembrolizumab monotherapy arm (HR 1.08; 95% CI, 0.85-1.37; P =.74). The median PFS was 8.2 months and 8.4 months for the combination and monotherapy arms, respectively (HR 1.06; 95% CI, 0.86-1.30; P =.72).
An overall response rate of 45.4% was observed in both treatment groups; median duration of response was 16.1 months in the combination arm compared with 17.3 months in the pembrolizumab monotherapy arm.
With regard to safety, a greater percentage of patients experienced treatment-related adverse events with the combination therapy compared with pembrolizumab monotherapy (76.2% vs 68.3%).
“KEYNOTE-598 is the first head-to-head study designed to answer the question of whether combining Keytruda with ipilimumab provided additional clinical benefits beyond treatment with Keytruda alone in certain patients with metastatic non-small cell lung cancer. The results are clear – the combination did not add clinical benefit but did add toxicity,” said Dr Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories.
Merck presents results from head-to-head phase 3 KEYNOTE-598 trial evaluating Keytruda® (pembrolizumab) in combination with ipilimumab versus Keytruda monotherapy in certain patients with metastatic non-small cell lung cancer. [press release]. Kenilworth, NJ: Merck; January 29, 2021.