Background

JAVELIN Lung 200, a randomized, open-label, phase III study, did not meet its primary endpoint of significantly improving overall survival (OS) with avelumab vs docetaxel in patients with PD-L1+ NSCLC. However, OS may have been affected by the larger proportion of patients in the docetaxel arm who received a subsequent CPI. We present post hoc analyses assessing the effect of subsequent CPIs on OS in the JAVELIN Lung 200 study.

Methods

Patients with stage IIIB/IV NSCLC and disease progression after platinum doublet treatment were randomized 1:1 to receive avelumab 10 mg/kg every 2 weeks or docetaxel 75 mg/m² every 3 weeks. The primary analysis population for OS was patients with PD-L1+ tumors (≥1% PD-L1 expression in tumor cells using the IHC 73-10 assay); OS was also analyzed in the full analysis set (FAS). To assess the impact of subsequent CPI treatment (after discontinuation of randomly assigned study treatment) on OS, a preplanned naive sensitivity analysis and a post hoc inverse probability of censoring weighted (IPCW) analysis were performed.

Results

A subsequent CPI (anti–PD-1, anti–PD-L1, or anti–CTLA-4) was received by 16/396 (4.0%) in the avelumab arm and 104/396 (26.3%) in the docetaxel arm in the FAS, including 15/264 (5.7%) and 70/265 (26.4%) in the PD-L1+ population, respectively. Median time to subsequent CPI was shorter in the docetaxel arm than the avelumab arm (5.68 vs 10.53 months; FAS). Hazard ratios for OS with avelumab vs docetaxel were lower in the IPCW model than in the primary analysis and naive sensitivity analysis, both in the FAS and in the PD-L1+ population (Table).Table:

1492P

Conclusions

IPCW analyses suggest that the primary OS analysis in this study was impacted by the relatively high proportion of patients in the docetaxel arm who received a subsequent CPI.

Clinical trial identification

NCT02395172.

Editorial acknowledgement

ClinicalThinking; funded by Merck Healthcare KGaA and Pfizer Inc.

Legal entity responsible for the study

Merck Healthcare KGaA.

Funding

Merck Healthcare KGaA and Pfizer Inc.

Disclosure

F. Barlesi: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Boehringer–Ingelheim; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Eli Lilly; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): F. Hoffmann–La Roche Ltd; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Novartis; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Pierre Fabre; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Takeda; Honoraria (institution): AbbVie; Honoraria (institution): ACEA; Honoraria (institution): Amgen; Honoraria (institution): Bayer; Honoraria (institution): Eisai; Honoraria (institution): Genentech; Honoraria (institution): Ipsen; Honoraria (institution): Ignyta; Honoraria (institution): Innate Pharma; Honoraria (institution): Loxo; Honoraria (institution): Sanofi-Aventis. M. Özgüroğlu: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy: Astellas; Travel / Accommodation / Expenses: Bristol-Myers Squibb. J.F. Vansteenkiste: Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Roche; Advisory / Consultancy: Apotex. D. Spigel: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy, Research grant / Funding (institution): Foundation Medicine; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck KGaA; Advisory / Consultancy: Moderna Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Nektar; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy: TRM Oncology; Advisory / Consultancy: Precision Oncology; Advisory / Consultancy: Evelo Therapuetics; Advisory / Consultancy: Illumina; Advisory / Consultancy: PharmaMar; Research grant / Funding (institution): University of Texas Southwestern Medical Center - Simmons Cancer Center; Research grant / Funding (institution): G1 Therapeutics; Research grant / Funding (institution): Neon Therapeutics; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono, Inc; Research grant / Funding (institution): Acerta Pharma; Research grant / Funding (institution): Oncogenex; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): GRAIL; Research grant / Funding (institution): Transgene; Research grant / Funding (institution): Aeglea Biotherapeutics; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): ARMO Biosciences; Research grant / Funding (institution): Millenium; Travel / Accommodation / Expenses: Genzyme; Travel / Accommodation / Expenses: Intuitive Surgical; Travel / Accommodation / Expenses: Purdue Pharma; Travel / Accommodation / Expenses: Spectrum Pharmaceuticals; Travel / Accommodation / Expenses: Sysmex. J.C. Yang: Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Roche/Genentech; Honoraria (self), Advisory / Consultancy: Chugai Pharmaceutical; Honoraria (self), Advisory / Consultancy: MSD; Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: Celgene; Advisory / Consultancy: Merrimack; Advisory / Consultancy: Yuhan Pharmaceuticals; Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Ono Pharmaceuticals; Advisory / Consultancy: Daiichi-Sankyo; Advisory / Consultancy: Hansoh Pharmaceuticals; Advisory / Consultancy: Takeda Pharmaceuticals; Advisory / Consultancy: Blueprint Medicines; Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: G1 Therapeutics. M. Bajars: Full / Part-time employment: EMD Serono, Inc. M. Ruisi: Full / Part-time employment: EMD Serono, Inc. J. Manitz: Full / Part-time employment: EMD Serono, Inc. K. Park: Advisory / Consultancy: AMGEN; Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: BluePrint; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: GSK; Advisory / Consultancy: Hanmi; Advisory / Consultancy: Kyowa Hakko Kirin; Advisory / Consultancy: Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Ono Pharmaceuticals; Advisory / Consultancy: Roche.