A Real-World, Multicenter, Observational Retrospective Study of Durvalumab After Concomitant or Sequential Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer.

Introduction: For unresectable stage III non-small cell lung cancer (NSCLC), the standard therapy consists of chemoradiotherapy (CRT) followed by durvalumab maintenance for responding patients. The present study reports on the safety and outcome of durvalumab use after CRT in a real-world, multicenter, retrospective cohort.
Methods: Two hundred thirty-eight patients have been included. We collected data on systemic therapy, radiation therapy, the timing between CRT and durvalumab, number of durvalumab cycles, reasons for non-starting or discontinuation, incidence and grade of adverse events (AEs), and progression-free survival (PFS) and overall survival (OS).
Results: One hundred fifty-five patients out of 238 (65.1%) received at least one durvalumab dose: 91 (58.7%) after concomitant CRT (cCRT) and 64 (41.3%) after sequential CRT (sCRT). Programmed-death ligand 1 (PD-L1) status was unknown in 7/155 (4.5%), negative in 14 (9.1%), and positive ≥1% in 134/155 (86.4%). The main reasons for non-starting durvalumab were progression (10.1%), PD-L1 negativity (7.5%), and lung toxicity (4.6%). Median follow-up time was 14 months (range 2–29); 1-year PFS and OS were 65.5% (95%CI: 57.6-74.4) and 87.9% (95%CI: 82.26.6-93.9), respectively. No significant differences in PFS or OS were detected for cCRT vs. sCRT, but the median PFS was 13.5 months for sCRT vs. 23 months for cCRT. Potentially immune-related AEs were recorded in 76/155 patients (49.0%). Pneumonitis was the most frequent, leading to discontinuation in 11/155 patients (7.1%).
Conclusions: Durvalumab maintenenace after concurrent or sequential chemoradiation for unresectable, stage III NSCLC showed very promising short-term survival results in a large, multicenter, restrospective, real-world study. Durvalumab was the first drug obtaining a survival benefit over CRT within the past two decades, and the present study contributes to validating its use in clinical practice.
Competing Interests: AB: speakers’ bureau from Astra Zeneca, MSD, Tecnologie Avanzate; and advisory role for Astra Zeneca. VS: speakers’ bureau for Astra Zeneca, Roche, Accuray Int.; and advisory role for Astra Zeneca. PB: speakers’ bureau for Astra Zeneca. SV: speakers’ bureau for Astra Zeneca, Roche, Accuray Int. ED’A: speaker’s bureau from Nestlè, MSD, Astra Zeneca; travel expenses: IPSEN; and expert testimony: Nestlè. NG: speakers’ bureau for Astra Zeneca. DF: speakers’ bureau for Astra Zeneca; and advisory role for AstraZeneca. FA: speakers’ bureau for Astra Zeneca, Roche, BMS, Boehringer Ingelheim, MSD; and advisory role for Boehringer Ingelheim, MSD. BJ-F: personal fees from Janssen, Roche, Astra Zeneca, and Accuray, and institutional grants from AIRC, FIEO-CCM and Accuray Int., all outside of the submitted work. ARF: speakers’ bureau for Astra Zeneca, MSD, Roche, Ipsen; advisory role for Astra Zeneca, Roche; institutional research funding: Astra Zeneca; and honoraria for study conduction (not related to the present study): Astra Zeneca. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Bruni, Scotti, Borghetti, Vagge, Cozzi, D’Angelo, Giaj Levra, Fozza, Taraborrelli, Piperno, Vanoni, Sepulcri, Trovò, Nardone, Lattanzi, Bou Selman, Bertolini, Franceschini, Agustoni, Jereczek-Fossa, Magrini, Livi, Lohr and Filippi.)