Real-World Outcomes and Safety of PD-1 Blockade Rechallenge Strategies After Prior Immunotherapy in Advanced NSCLC: A Retrospective Cohort Study.

[OBJECTIVE] Evidence to guide treatment after progression on immunotherapy remains limited in advanced non-small cell lung cancer (NSCLC). We descriptively report real-world outcomes of two PD-1 rechallenge strategies (PD-1 plus chemotherapy and PD-1 plus anlotinib) using a contemporaneous docetaxel cohort as contextual reference.

[METHODS] Patients with advanced NSCLC who failed prior immunotherapy were screened retrospectively, 33 patients received PD-1 blockade plus chemotherapy, 31 received PD-1 blockade plus anlotinib and 63 patients treated with docetaxel monotherapy were served as a contextual reference cohort. Outcomes including objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were summarized by cohort. Survival outcomes were estimated using Kaplan-Meier methods.

[RESULTS] ORR and DCR were 30.3% (95% CI: 15.6%-48.7%) and 84.8% (95% CI: 68.1%-94.9%) in PD-1 plus chemotherapy cohort, 22.6% (95% CI: 9.6%-41.1%) and 80.6% (95% CI: 62.5%-92.5%) in PD-1 plus anlotinib cohort, 15.9% (95% CI: 7.9%-27.3%) and 54.0% (95% CI: 40.9%-66.6%) in docetaxel cohort. Median DoR among responders was 6.9 months (95% CI: 0.7-13.1), 7.1 months (95% CI: 5.0-9.2), and 3.1 months (95% CI: 1.9-4.3), respectively. Median PFS was 7.0 months (95% CI: 0.7-13.3), 6.5 months (95% CI: 2.2-10.8), and 3.3 months (95% CI: 2.2-4.4), and median OS was 17.8 months (95% CI: 8.0-27.6), 16.8 months (95% CI: 13.9-19.7), and 9.5 months (95% CI: 4.8-14.2), respectively. Any-grade TRAEs occurred in 84.8%, 80.6%, and 81.0%, and grade ≥3 TRAEs were 42.4%, 41.9%, and 34.9%, respectively. No treatment-related deaths were observed.

[CONCLUSION] PD-1 rechallenge strategies showed measurable antitumor activity and manageable safety profile in a subset of previously immunotherapy-treated advanced NSCLC. Limitations existed in this study and the findings were descriptive and hypothesis-generating and should be interpreted cautiously because treatment selection was non-random and important confounders might be incompletely captured.