Impact of subsequent immune checkpoint inhibitor treatment on overall survival with avelumab vs docetaxel in platinum-treated advanced NSCLC: Post hoc analyses from the phase 3 JAVELIN Lung 200 trial

Keunchil Park (1) , Mustafa Özgüroğlu (2) , Johan Vansteenkiste (3) , David Spigel (4) , James C.H. Yang (5) , Marcis Bajars (6) , Mary Ruisi (6) , Juliane Manitz (6) , Fabrice Barlési (7, 8)

1 Samsung Medical Center Sungkyunkwan University School of Medicine
2 Istanbul University Cerrahpasa
3 Department of Pulmonology
4 Sarah Cannon Research Institute [Nashville, Tennessee]
5 National Taiwan University Cancer Center [Taipei]
6 EMD Serono Research & Development Institute
7 Département de médecine oncologique [Gustave Roussy]
8 CRCM - Centre de Recherche en Cancérologie de Marseille

The JAVELIN Lung 200 phase 3 trial did not meet its primary endpoint of improving overall survival (OS) with avelumab vs docetaxel in patients with platinum-treated PD-L1+ NSCLC. We report post hoc analyses assessing the effects of subsequent immune checkpoint inhibitor (ICI) treatment on OS. Material and methods: Patients with stage IIIB/IV NSCLC progressed following platinum-doublet therapy were randomized to receive avelumab or docetaxel. OS was analyzed in the PD-L1+ population (≥1% of tumor cells) and full analysis set (PD-L1+ or PD-L1−). Effects of subsequent ICI (after permanent discontinuation of study treatment) on OS were analyzed using a preplanned naive sensitivity analysis and post hoc inverse probability of censoring weighting (IPCW) analysis. Subgroups with or without subsequent ICI treatment were analyzed using descriptive statistics. Results: In the avelumab and docetaxel arms, a subsequent ICI was received by 16/396 (4.0 %) and 104/396 (26.3 %) after a median of 10.5 months (range, 3.9-20.4) and 5.7 months (range, 0.1-24.4), respectively. Some subgroups showed trends for higher subsequent ICI treatment, including patients with non-squamous NSCLC (avelumab arm, 4.3 % vs docetaxel arm, 32.1 %) or with a baseline ECOG performance status of 0 (6.3 % vs 31.3 %); those enrolled in the early recruitment wave (11.6 % vs 54.3 %), or enrolled in the US/Western Europe (2.8 % vs 45.5 %) or Asia (11.0 % vs 35.4 %); and non-white patients (10.1 % vs 35.0 %). The hazard ratio for OS with avelumab vs docetaxel was lower in the IPCW analysis than in the naive sensitivity analysis (PD-L1+ population: 0.80 [95 % CI, 0.62− 1.04] vs 0.86 [95 % CI, 0.68− 1.09], respectively). Conclusion: In the JAVELIN Lung 200 trial, avelumab showed clinical activity as second-line treatment for patients with advanced NSCLC. Post hoc analyses suggest that the primary OS analysis may have been confounded by subsequent ICI use in the docetaxel arm. ClinicalTrials.gov identifier: NCT02395172.

Keywords: Clinical trial CI; confidence interval; ECOG PS; Eastern Cooperative Oncology Group performance status; EGFR; epidermal growth factor receptor; HR; hazard ratio; ICI; immune checkpoint inhibitor; Ig; immunoglobulin; IHC; immunohistochemistry; IPCW; inverse probability of censoring weighting; IRC; independent review committee; KEAP1; kelch-like ECH associated protein 1; NR; not reached; NSCLC; non-small cell lung cancer; OS; overall survival; PD-1; programmed cell death 1 protein; PD-L1; programmed cell death 1 ligand 1; PFS; progression-free survival; STK11; serine/threonine kinase 11

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Immunology; Immunotherapy

Keunchil Park, Mustafa Özgüroğlu, Johan Vansteenkiste, David Spigel, James C.H. Yang, et al.. Impact of subsequent immune checkpoint inhibitor treatment on overall survival with avelumab vs docetaxel in platinum-treated advanced NSCLC: Post hoc analyses from the phase 3 JAVELIN Lung 200 trial. Lung Cancer, 2021, 154, pp.92 - 98. ⟨10.1016/j.lungcan.2021.01.026⟩. ⟨hal-03245801⟩