Outcomes of anti–PD-(L)1 therapy with or without chemotherapy (chemo) for first-line (1L) treatment of advanced non–small cell lung cancer (NSCLC) with PD-L1 score ≥ 50%: FDA pooled analysis.

Abstract

9000 Background: FDA-approved 1L treatment options for patients with PD-L1-high advanced NSCLC (PD-L1 score ≥50%) include IO ± chemo (± anti-angiogenics) but it is unclear if chemo substantially improves efficacy outcomes when added to IO in this patient population. Methods: Data was pooled from 12 randomized controlled trials that investigated anti-PD-(L)1 regimens ± chemo for the 1L treatment of patients with advanced NSCLC. PD-L1 score was defined as the proportion of tumor cells stained by the assay and analysis was conducted for patients with tumor PD-L1 score ≥50%. OS, PFS, and ORR were compared between chemo-IO and IO alone via a pooled analysis. Median survival times were estimated using Kaplan-Meier methods. Hazard ratios were estimated using Cox proportional hazards models stratified by trial; odds ratios were estimated using a logistic regression model with trial as a covariate. All analyses were adjusted for age, sex, race, ECOG, histology and smoking status. Results: A total of 3,189 patients with NSCLC and PD-L1 score ≥50% were identified for this analysis. Baseline characteristics were: 38% ages 65-74 years and 11% ages ≥75 years; 69% male; 80% White; 66% ECOG ≥1; and 89% former/current smokers. Median OS in the pooled chemo-IO ( N=455) and IO-only ( N=1,298) arms was 25.0 vs 20.9 months (HR 0.82; 95% CI: 0.62, 1.08); median PFS was 9.6 vs 7.1 months, respectively (HR 0.69; 95% CI: 0.55, 0.87). ORR was higher with chemo-IO than with IO alone (61% vs 43%; Odds ratio 1.2, 95% CI: 1.1, 1.3). Conclusions: This exploratory, hypothesis-generating pooled analysis suggests that most subgroups of patients with advanced NSCLC with PD-L1 score ≥50% receiving FDA-approved chemo-IO regimens may have OS and PFS outcomes that are comparable with or better than IO-only regimens. Patients ≥75 years of age receiving chemo-IO may not have improved outcomes over IO. These results support shared decision-making that balances potential benefits and risks of adding chemo to IO regimens based on patient factors that may impact tolerability. [Table: see text]

Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Metastatic Non–Small-Cell Lung Cancer in CheckMate 227

“…26 A recent pooled analysis suggested that most patient subgroups with PD-L1 $ 50% receiving FDA-approved immunotherapy and chemotherapy combinations had comparable survival outcomes versus immunotherapy only although of note, dual nivolumab plus ipilimumab was included in the immunotherapy-only group together with anti-PD-(L)1 monotherapies, confounding direct extrapolations. 27 Overall, the optimal regimen for the PD-L1 $ 50% subgroup is unclear, highlighting the importance of considering both risks and benefits of different treatments in individual patients. With nivolumab plus ipilimumab, 18% of patients in CheckMate 227 overall discontinued treatment because of TRAEs, which is not substantially higher than the 14% pembrolizumab discontinuation rate for patients with PD-L1 $ 50% in KEYNOTE-024.…”

Lung cancer in never smokers: Tumor immunology and challenges for immunotherapy

“…In the FDA pooled analysis of outcomes of anti-PD-(L)1 therapy (IO) with or without chemotherapy (chemo) for first line treatment of patients with NSCLC and PD-L1 score ≥50% ( 80 ), never-smokers appeared to have better results with the association of IO-chemo in all the outcomes evaluated: median OS NE vs 14.4 months (HR 0.39, 0.15-0.98), median PFS 10.2 vs 3.7 months (HR 0.46, 0.23-0.92) and ORR 69% vs 28% (OR 4.6, 1.5-14.5).…”

ASCO-Update zum nicht-kleinzelligen Lungenkarzinom

“…In der ersten Analyse wurden von der FDA zugelassene Regime für Tumoren ohne genetische Alterationen darauf untersucht, ob bei einer PD-L1-Expression ≥ 50 % die Notwendigkeit der Kombination einer immunonkologischen Substanz mit einer Chemotherapie notwendig ist 1 . In die Auswertung flossen die Daten von 9084 therapienaiven NSCLC-Patienten aus 12 randomisierten Studien ein, von denen 3189 Patienten einen PD-L1-Score ≥ 50 % aufwiesen.…”

“…Durch die ständig fortschreitende Entwicklung neuer Wirksubstanzen und die Untersuchung neuer Kombinationen in unterschiedlichen Therapielinien bedarf es einer ständigen Überarbeitung des Therapiealgorithmus. Die amerikanische Behörde FDA (U. S. Food and Drug Administration) präsentierte auf dem ASCO 2022 in 2 Vorträgen die Analyse der eingereichten Daten zur Optimierung der Erstlinientherapie beim fortgeschrittenen nicht-kleinzelligen Lungenkarzinom (NSCLC) 1 , 2…”