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Checkmate 227 plus#
With all patients off immunotherapy treatment for 2 years or longer, no new TRAEs were reported in the nivolumab plus ipilimumab arm since the previous database lock the incidence of any-grade and grade 3 or 4 TRAEs, serious TRAEs, and TRAEs leading to discontinuation in all treatment arms was largely unchanged from previous reports ( Supplementary Table 4). In the subset of patients with tumor PD-L1 expression greater than or equal to 50%, ORRs were 45% with nivolumab plus ipilimumab and 37% with nivolumab monotherapy median DOR was 31.8 months and 16.8 months, respectively ( Fig. 3 C and D). Among patients with PD-L1 greater than or equal to 1%, ORRs were 36% with nivolumab plus ipilimumab and 28% with nivolumab monotherapy median DOR was 23.2 months and 15.5 months, respectively. Nivolumab plus ipilimumab versus nivolumab monotherapy separations increased with time and were maintained at 4 years for both PD-L1 greater than or equal to 1% (OS rates, 29% and 21% PFS rates, 14% and 10%) and PD-L1 greater than or equal to 50% populations (OS rates, 37% and 26% PFS rates, 20% and 14%). The OS curves of nivolumab plus ipilimumab and nivolumab monotherapy separated approximately 12 months (PD-L1 ≥1%) or 18 months (PD-L1 ≥50%) from randomization ( Fig. 1 A and B) and PFS curves separated approximately 6 months from randomization, favoring nivolumab plus ipilimumab over time ( Fig. 3 A and B). Nivolumab plus ipilimumab showed numerically higher benefit across all efficacy end points compared with nivolumab monotherapy (descriptive analysis) in patients with tumor PD-L1 expression greater than or equal to 1% and in the subset with tumor PD-L1 expression greater than or equal to 50%. Patients who discontinued nivolumab plus ipilimumab due to TRAEs had long-term OS benefits, as seen in the all randomized population.
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The most common immune-mediated AE with nivolumab plus ipilimumab, nivolumab, and nivolumab plus chemotherapy was rash most immune-mediated AEs (except endocrine events) occurred within 6 months from start of treatment and resolved within 3 months after, mainly with systemic corticosteroids. Safety was consistent with previous reports. In a descriptive analysis, efficacy was improved with nivolumab plus ipilimumab relative to nivolumab (PD-L1 ≥1%) and nivolumab plus chemotherapy (PD-L1 <1%). Benefits were observed in both squamous and nonsquamous histologies. After 54.8 months' median follow-up, OS remained longer with nivolumab plus ipilimumab versus chemotherapy in patients with PD-L1 greater than or equal to 1% (hazard ratio = 0.76 95% confidence interval: 0.65–0.90) and PD-L1 less than 1% (0.64 0.51–0.81) 4-year OS rate with nivolumab plus ipilimumab versus chemotherapy was 29% versus 18% (PD-L1 ≥1%) and 24% versus 10% (PD-L1 <1%).