Effectiveness of PD-(L)1 Inhibitors Alone or in Combination With Platinum-Doublet Chemotherapy in First-Line (1L) Non-Squamous Non-Small Cell Lung Cancer (nsq-NSCLC) With PD-L1-High Expression Using Real-World Data

BACKGROUND: Anti-PD-(L)1 therapy alone (cancer immunotherapy [CIT]-mono) or combined with platinum-based chemotherapy (CIT-chemo) is used as first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC). Our study compared clinical outcomes with CIT-mono vs CIT-chemo in the specific clinical scenario of non-squamous (Nsq)-NSCLC with a high PD-L1 expression of ≥50\% (tumor proportion score (TPS) or tumor cells (TC)). METHODS: This was a retrospective cohort study using a real-world de-identified database. Patients with metastatic Nsq-NSCLC with high PD-L1 expression initiating first-line CIT-mono or CIT-chemo between 24 October 2016 and 28 February 2019 were followed up to 28 February 2020. We compared overall survival (OS) and real-world progression-free survival (rwPFS) using Kaplan-Meier methodology. Hazard ratios (HR) were adjusted (aHR) for differences in baseline key prognostic characteristics using inverse probability of treatment weighting methodology. RESULTS: Patients with PD-L1-high Nsq-NSCLC treated with CIT-mono (n=351), were older and less often presented with de novo stage IV disease than patients treated with CIT-chemo (n=169). With a median follow-up of 19.9 months for CIT-chemo vs 23.5 months for CIT-mono, median OS and rwPFS did not differ between the two groups (median OS: CIT-chemo, 21.0 months vs CIT-mono, 22.1 months, aHR=1.03, 95\% CI 0.77-1.39, P=0.83; median rwPFS: CIT-chemo, 10.8 months vs CIT-mono, 11.5 months, aHR=1.04, 95\% CI 0.78-1.37, P=0.81). CIT-chemo showed significant and meaningful improvement in OS and rwPFS vs CIT-mono only in the never-smoker subgroup, albeit among a small sample of patients (n=50; OS HR=0.25, 95\% CI 0.07-0.83, interaction P=0.02; rwPFS HR=0.40, 95\% CI 0.17-0.95, interaction P=0.04). CONCLUSION: Except in the subgroup of never-smoker patients, sparing the chemotherapy in first-line CIT treatment does not appear to impact survival outcomes in Nsq-NSCLC patients with high PD-L1 expression.