First-line durvalumab in patients with PD-L1 positive, advanced non-small cell lung cancer (NSCLC) with a performance status of 2 (PS2). Primary analysis of the multicenter, single-arm phase II trial SAKK 19/17.

The safety and efficacy of first-line durvalumab in PS2 patients with advanced NSCLC is unknown. Here, we present the primary analysis of first-line durvalumab in PS2 patients, unsuitable for combination chemotherapy. In this single-arm, multicenter, phase II trial patients with PD-L1 positive (tumor proportional score ≥25%), advanced NSCLC with PS2, received four-weekly durvalumab 1500 mg. The primary endpoint was overall survival (OS) at 6 months. Forty-eight patients were included. Median follow-up was 23.3 months (95% CI: 14.3-28.6). OS at 6 months was 60% (95% CI: 45-74%). Median OS was 8.5 months (95%CI: 4.4-16.7). Objective response rate and median progression free survival were 17% (95% CI: 8-30%) and 2.5 months (95% CI: 1.8-7.1), respectively. Thirty-three deaths were observed at the time point of the analysis. Seven early fatal events considered not treatment-related occurred during the first 5 weeks of treatment. Four out of the first 7 early fatal events (4/7; 57%) were respiratory failure in patients with advanced symptomatic primary lung tumors. Three more early fatal events occurred after exclusion of patients with grade ≥ 3 dyspnea. Treatment-related AEs ≥G3 were reported in 9 patients (19%) and included colonic perforation in one patient (grade 5), colitis in 4 patients (8%), increased lipase in 3 patients (6%), and hepatitis in 2 patients (4%). First-line durvalumab in PS2 patients with advanced PD-L1 positive NSCLC results in a high number of early fatal events. When patients with grade ≥ 3 dyspnea are excluded a promising 6-month OS with an acceptable toxicity profile can be observed. Durvalumab could be an option instead of single agent chemotherapy for PS2 patients who are not candidates for platinum doublet chemotherapy provided they are well selected.

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Déclaration de conflit d'intérêts

Declaration of Competing Interest Michael Mark: consulting fees: Amgen, Astra Zeneca, BMS, MSD, Pfizer, Takeda, Roche, Travel support: Astra Zeneca, Roche, Takeda. Patrizia Froesch: consulting fees: Janssen, Sanofi, Takeda, Roche, Travel support: Merck. Katrin Gysel: no conflict of interest. Sacha I. Rothschild: consulting fees: Astra Zeneca, BMS, MSD, Pfizer, Böringer Ingelheim, Eisei, Eli Lilly, Honoraria: Roche, Astra Zeneca. Alfredo Addeo: consulting fees: Amgen, Astra Zeneca, Astellas, BMS, MSD, Pfizer, Novartis, Takeda, Roche, Honoraria: Amgen, Novartis. Christoph J. Ackermann:: no conflict of interest. Sabrina Chiquet: no conflict of interest. Martina Schneider: no conflict of interest. Karin Ribi: no conflict of interest. Angela Fischer Maranta: consulting fees: Merck, Travel support: Amgen, Janssen. Sara Bastian: consulting fees: Astra Zeneca, BMS MSD, Travel support: Servier, Astra Zeneca, Roche. Roger von Moos: consulting fees: Amgen, Roche, Gilead, Pierre Fabre Pharma Mar, Sanofi, MSD, Eli Lilly, Merck, Vifor, GSK, Travel support: Pierre Fabre, Takeda, research grants: Bayer. Markus Joerger: consulting fees: Astra Zeneca, Novartis, BMS, MSD, Sanofi, Merck, Roche, Basilea Pharmaceutical, Innomedica, research grants: Astra Zeneca, Roche, Takeda, Daiichi Sancho, Basilea Pharmaceutical, Pfizer, Pharma Mar, Sanofi, BMS, Jannsen, Innomedica, Merck, Eli Lilly, Immunophotonics. Martin Früh: consulting fees: Astra Zeneca, BMS, MSD, Roche, Böhringer Ingelheim, Pfizer, Takeda, research grants: Astra Zeneca, MSD.