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

Ling-Jie Zheng,1 Yan-Li Shen,2 Hong-Wei Zhao,1 Yong-Cheng Ma,1 Ai-Feng Wang1 1Department of Pharmacy, Fuwai Central China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University, Henan Key Laboratory of Individualized Drug Therapy for Cardiovascular Diseases, Zhengzhou, Henan, 450046, People’s Republic of China; 2Department of Respiratory Medicine, Fuwai Central China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan, 450046, People’s Republic of ChinaCorrespondence: Ai-Feng Wang, Department of Pharmacy, Fuwai Central China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University, Henan Key Laboratory of Individualized Drug Therapy for Cardiovascular Diseases, No. 1 Fuwai Avenue, Zhengdong New District, Zhengzhou, Henan, 450046, People’s Republic of China, Tel +86-18538298379, Email [email protected] Yong-Cheng Ma, Department of Pharmacy, Fuwai Central China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University, Henan Key Laboratory of Individualized Drug Therapy for Cardiovascular Diseases, No. 1 Fuwai Avenue, Zhengdong New District, Zhengzhou, Henan, 450046, People’s Republic of China, Tel +86-18639558715, Email [email protected]: 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.Keywords: non-small cell lung cancer, previously immunotherapy-treated, PD-1 blockade, chemotherapy, anlotinib, docetaxel, therapeutic outcomes, safety