Pembrolizumab (Keytruda) combined with ipilimumab (Yervoy) did not improve survival and had higher levels of toxicity compared to pembrolizumab monotherapy as a first-line treatment for patients with non-small metastatic lung cancer (NSCLC) with PD- L1 scored a score (TPS) of 50% or more, and did not port EGFR no ALK aberrations, according to the results of a KEYNOTE-598 level 3 test presented at the International Society for the Study of Lung Cancer 2020 on lung cancer.
Results showed that the total overall survival rate (OS) for patients who received pembrolizumab / ipilimumab was 21.4 months versus 21.9 months for those who received the PD-1 inhibitor alone (HR, 1.08; 95% CI, 0.85–1.37; P. = .74). The limited differences were survival time –0.56 at peak and –0.52 at 2 years, which met the income criteria of the study.
Moreover, the survival rate without improvement (PFS) was 8.2 months and 8.4 months for the combination and arm monotherapy, respectively (HR, 1.06; 95% CI, 0.86–1.30; P. = .72).
Based on the efficacy and safety observed, an external data review committee recommended that the study be discontinued due to income and that patients discontinue treatment from both ipilimumab and placebo. , explained study author Michael Boyer, MBBS FRACP PhD.
“As a result of the results of this study, monotherapy with pembrolizumab remains the standard of care for this population of patients,” said Boyer, clinical professor of medicine at Chris O’Brien Life and Central University Clinical School. Sydney, in Sydney, Australia. “Despite the benefits of this type of treatment, almost 50% of these patients die from their disease within two years, so future research will ‘focus on other ways to improve outcomes.’
In the multicenter, KEYNOTE-598 level 3 test (NCT03302234), which consisted of centers in North America, Europe, and Asia, researchers tried to find out could ipilimumab be added to pembrolizumab efficacy against single-agent pembrolizumab in patients with metastatic NSCLC with at least 50% PD-L1 TPS and no port EGFR no ALK aberrations.
Patients were randomized 1: 1 to receive pembrolizumab at 200 mg every 3 weeks for up to 35 cycles with ipilimumab at 1 mg / kg every 6 weeks (n = 284) or saline placebo (n = 284) for up to 6 cycles. Stratification factors included ECOG performance score (0 vs 1), region (East Asia vs non-East Asia), and histology (squamous vs nonsquamous). The main endpoints were PFS and OS, both of which were assessed by the serial log status test in the population intending to treat.
The first protocol-specified interim study was expected to occur in approximately 255 deaths and approximately one year had elapsed since the last patient was randomized to treatment. Non-binding income criteria at this analysis were differences in the average median survival time between the combination and pembrolizumab / placebo of less than or equal to 0.2 at the time highest observation and less than or equal to 0.1 at 2 years of follow-up.
In addition, 372 incidents for SDP and 272 deaths occurred during this period.
Further data showed that the target response rate was 45.4% in all arms. The median duration of response was 16.1 months and 17.3 months for the ipilimumab / pembrolizumab and placebo / pembrolizumab groups, respectively.
In terms of safety, 76.2% of treatment-related adverse events were in the ipilimumab / pembrolizumab group compared with 68.3% for the pembrolizumab / placebo arm.
Information
- Boyer M. Pembrolizumab plus ipilimumab vs pembrolizumab plus placebo as 1L therapy for metastatic NSCLC of PD-L1 TPS ≥50%: KEYNOTE-598. Presented at: International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer; January 28-31, 2021; significant. Abstract PS01.09