1L Nivolumab + Ipilimumab Show Durable Efficacy Vs. Chemo In Metastatic NSCLC Patients

The phase 3 study enrolled adults with treatment-naive stage IV or recurrent non-small cell lung cancer (NSCLC) who had no known EGFR/ALK alterations and had an ECOG performance status of ≤1. Patients (pts) with tumor PD-L1 expression ≥1% were randomly assigned to receive either nivolumab + ipilimumab, nivolumab alone, or chemotherapy. Patients with tumor PD-L1 expression <1% were randomly assigned to receive nivolumab + ipilimumab, nivolumab + chemotherapy, or chemotherapy alone.

Assessments included OS (overall survival), PFS (progression-free survival), ORR (overall response rate), DOR (duration of response), and OS categorized by best response and the reduction in tumor burden from baseline (responders: complete or partial response [CR/PR] with ≥80% reduction, PR with 50-<80% reduction, or PR with 30-<50% reduction; non-responders: stable or progressive disease). Additionally, the researchers examined baseline health-related quality of life (HRQoL) using EQ-5D-3L, where higher scores indicated better HRQoL.

After a minimum follow-up period of 73.5 months (database locked on February 21, 2023), nivolumab + ipilimumab consistently demonstrated improved OS compared to chemotherapy, regardless of tumor PD-L1 expression. At the 6-year mark, the OS rates were 22% vs. 13% and 16% vs. 5%, respectively, for tumor PD-L1 expression ≥1% and <1%. We observed a consistent clinical benefit across various efficacy endpoints in all pts, regardless of their tumor’s PD-L1 expression, as well as in pts who survived for 6 years.

A greater proportion of responders experienced tumor burden reduction of ≥80% with nivolumab + ipilimumab compared to chemotherapy (tumor PD-L1 ≥1%, 15% vs. 3%; tumor PD-L1 <1%, 8% vs. 1%). Additionally, the 6-year OS rates were notably higher in these responder groups (59% vs. 42%; 77% vs. 0%). Among pts who completed EQ-5D-3L visual analog scale assessments with a minimum follow-up period of 5 years (61.3 months) (n=1073), those with higher baseline scores, relative to the median, had longer median OS (95% CI) regardless of treatment (nivolumab + ipilimumab, 19.7 [16.7-23.9] vs. 14.9 [12.2-18.1] months; chemotherapy, 17.8 [15.0-19.8] vs. 10.1 [7.8-12.2] months). We will provide further details on OS categorized by response/tumor burden reduction in additional categories and updated 6-year HRQoL data. No new safety concerns emerged.

This 6-year update represented the most extensive follow-up data among first-line immunotherapy trials for metastatic NSCLC. Nivolumab + ipilimumab sustained its long-term and enduring efficacy benefits over chemotherapy in pts with tumor PD-L1 expression ≥1% or <1%—a population with significant unmet medical needs. Responders who experienced substantial tumor burden reduction also enjoyed a more pronounced long-term OS benefit with nivolumab + ipilimumab compared to chemotherapy. Furthermore, better baseline HRQoL was associated with improved OS.

Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/959

Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02477826

Ramalingam, S.S., Ciuleanu, T-E., Caro, R. B, Nishio, M., Mizutani, H., Lee, J-S., Audigier-Valette, C., Sangha, R., Urban, L., Burgers, J.A., Pluzanski, A., Lee, K.H., Zurawski, B., Schenker, M., Peters, S., Paz-Ares, L.G., Borghaei, H., O’Byrne, K.J., Brahmer, J.R., Gupta, R.G., Bushong, J., Li, L., Yuan, Y., Blum, S.I., Reck, M. Six-year Survival and HRQoL Outcomes with 1L Nivolumab + Ipilimumab in Patients with Metastatic NSCLC from CheckMate227.