e20578 Background: The use of ICIs, as monotherapy (mono) or with platinum-based chemotherapies, is the 1L standard of care for patients with mNSCLC without actionable genomic alterations. However, many patients progress during or shortly after ICI therapy, and the benefit of ICI retreatment in 2L is not clear. This study investigated 2L outcomes among responders and non-responders to 1L ICI. Methods: This retrospective study used ConcertAI Patient360 NSCLC dataset and included patients who received any ICI from the start of 2L who also received an ICI in 1L (from 01/2020-02/2025), based on a progression-based line of therapy algorithm. Patients were defined as 1L responders (first disease assessment was complete/partial response) or non-responders (first disease assessment was progression). Patients with stable disease only or no response assessment were excluded. Median real-world overall survival (rwOS) and progression-free survival (rwPFS) were compared with Kaplan-Meier analysis, with the start of 2L as index date. Results: 459 patients met eligibility criteria: 243 (53%) were classified as responders and 216 were non-responders. Patients were non-Hispanic (88%), White (83%), and 49% were male. 71% had non-squamous NSCLC, and most had ECOG 0-1 (67%), were current/former smokers (90%), and treated in community centers (80%). Of the 79% of patients tested for PD-L1 prior to 2L start, approximately 25% had TPS ≥50%. Responders tended to be older than non-responders and have de novo mNSCLC (86% vs 79%). Treatments were similar among the two groups; overall, 43% received pembrolizumab (pembro)+platinum doublet as their first treatment, 22% received pembro mono. The most common 2L regimens were pembro mono (31%) and pembro+pemetrexed (19%), with 29 additional unique regimens observed. No significant difference was seen in median 2L rwPFS for responders (5.3 months, 95% Confidence Interval CI: 4.4, 5.9) compared to non-responders (4.6 months, 95% CI: 4.0, 5.5), or 2L rwOS for responders (12.9 months, 95% CI: 11.2, 14.9) versus non-responders (11.7 months, 95% CI: 9.8, 14.3). However, among the responders, patients with >2 months treatment-free interval from end of 1L to progression (n=63) had significantly longer median 2L rwOS (15.9 months, 95% CI: 14.2, 20.4) than patients who progressed earlier (n=180; 11.8 months, 95% CI: 9.3, 13.1; p=0.02). Conclusions: Response to 1L ICI was not associated with patient outcomes on 2L ICI. However, patients who maintained their response for >2 months after 1L ICI discontinuation had significantly longer rwOS than those who progressed earlier. Further research is needed to identify which patients with 1L ICI are most likely to respond to ICI in 2L and to compare outcomes with patients receiving other agents in 2L.
Wonsettler et al. (Thu,) studied this question.
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