A prospective study on clinicians' attitudes and survival outcomes for patients with advanced NSCLC and poor performance status in the immunotherapy era: PICASO (GOIRC-04-2020)

Background: Therapeutic strategies for patients with advanced NSCLC and an ECOG performance status (PS) 2 at diagnosis are supported by limited evidence. Patients and methods: We led a prospective, observational study in 20 Italian centers on patients with advanced NSCLC and ECOG PS 2. Patients with EGFR mutations, ALK fusions or receiving first-line targeted treatments were excluded. We recorded physicians' attitudes in addressing first-line treatments and clinical outcomes. The primary endpoint was progression-free rate at six months. Results: From March 2022 to October 2023, 198 consecutive patients were included. Median age was 73 years (range 43-91). Forty-four patients (22%) were candidate to best supportive care, 49 (25%) to single agent chemotherapy, 14 (7%) to platinum doublet, 40 (20%) to mono-immunotherapy, 52 (26%) to chemo-immunotherapy. At a median follow-up of 9.4 months (95 % CI 7.2 - 11.7), 6-month progression-free rate was 15.3%, with a median progression-free survival of 1.6 months (95 % CI 1.3 - 1.9). Six-months overall survival (OS) rate was 27.7%, with a median OS of 2.8 months (95 % CI 2.0 - 3.6). Patients receiving chemo-immunotherapy (PD-L1 < 50%) had 6-month progression-free and OS rates of 22.9% and 29.1% respectively, with median PFS 1.9 months and median OS 3.7 months; mono-immunotherapy for patients with PD-L1 ≥ 50% led to slightly better outcomes. Among 155 patients receiving active treatment, no clinical-pathological characteristic harbored a prognostic role. One third of patients receiving immunotherapy-containing regimens encountered early clinical progression or death before the first radiological evaluation. No relevant safety signals emerged across treatments. Conclusions: Less than half of patients with NSCLC and ECOG PS 2 were candidates to the regimens recommended for fit pts, i.e. mono-immunotherapy or chemo-immunotherapy according to PD-L1. Even with immunotherapy, most of these patients have dismal outcomes, suggesting that trials dedicating to PS 2 perform an intrinsic patient selection.