Exploring the Role of Immunotherapy-Based Treatments for Advanced Non-Small-Cell Lung Cancer With Novel Driver Alterations.

Background: Immunotherapy (IO) single agent or combined with chemotherapy (CT-IO) is the standard treatment for advanced non-small-cell lung cancer (aNSCLC) without driver alterations. IO efficacy in patients with novel driver alterations is not well reported.
Materials and Methods: Data of aNSCLC patients treated with IO or CT-IO in any line from January 2016 to September 2022 were retrospectively collected. Patients harboring novel driver alterations (m-cohort), including MET exon 14 skipping, BRAF (V600E or atypical), RET rearrangements, HER2 point mutations/exon 20 insertions or uncommon EGFR mutations/EGFR exon 20 insertions, and wild type patients (wt-cohort) were eligible. Clinico-pathological data were extracted from Institutional databases and compared through chi square or Fisher's exact test. Survivals were estimated through Kaplan-Meier method and compared by log-rank test.
Results: m-cohort and wt-cohort included 84 and 444 patients, respectively. Progression free survival (PFS) was 5.53 vs. 4.57 months (P= .846) and overall survival (OS) was 25.1 vs. 9.37 months, (P < .0001) for m-cohort compared to wt-cohort. Within the m-cohort, BRAF atypical mutations had the better outcomes (Overall Response Rate [ORR], PFS), targeted agents timing did not affect response to IO and CT-IO had better ORR and disease control rate (DCR) compared to IO single agent (P = .0160 and P = .0152). In the PD-L1≥50% group, first line IO single agent resulted in inferior ORR (P = .027) and PFS (P = .022) in m-cohort compared to wt-cohort.
Conclusion: IO based treatments seem not detrimental for patients harboring novel driver alteration. Adding CT could improve modest responses to IO alone. Confirmation on larger datasets is required.
Competing Interests: Disclosure Diego Signorelli declares personal fees from AstraZeneca, Merck Sharp and Dohme, Boehringer Ingelheim, BMS, Roche and Sanofy. Arsela Prelaj declares personal fees from AstraZeneca, Italfarmaco, F. Hoffmann-La Roche, BMS. Roberto Ferrara declares advisory role from Merck Sharp and Dohme. Claudia Proto declares personal fees from Italfarmaco, AstraZeneca, BMS and Merck Sharp and Dohme. Giuseppe Lo Russo provided consultation, attended advisory boards and/or provided lectures for the following organizations, from whom received honoraria or education grants: Merck Sharp and Dohme, Takeda, Amgen, Eli Lilly, B.M.S., F. Hoffmann-La Roche, Italfarmaco, Novartis, Sanofi, Pfizer, G.S.K. and AstraZeneca. Marina Chiara Garassino declares personal financial interests with the following organizations: AstraZeneca, Merck Sharp and Dohm, International GmbH, BMS, Boehringer Ingelheim Italia S.P.A, Celgene, Eli Lilly, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, F. Hoffmann-La Roche, Takeda, Seattle Genetics, Mirati, Daiichi Sankyo, Regeneron, Merck, Ose Immuno Therapeutics, Blueprint, Jansenn, Sanofi; she also declares Institutional financial interests with the following organizations: Eli Lilly, Merck Sharp and Dohm, Pfizer (MISP); AstraZeneca, MSD International GmbH, BMS, Boehringer Ingelheim Italia S.P.A, Celgene, Eli Lilly, Ignyta, Incyte, MedImmune, Novartis, Pfizer, Roche, Takeda, Tiziana, Foundation Medicine, Glaxo Smith Kline GSK, Spectrum pharmaceuticals. Paolo Marchetti provided consultation, attended advisory boards and/or provided lectures for the following organizations, from whom received honoraria or education grants: F. Hoffmann-La Roche, Merck Sharp and Dohme, BMS, AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Novartis and Pfizer. Filippo de Braud provided consultation, attended advisory boards and/or provided lectures for the following organizations, from whom received honoraria or education grants: Amgen, AstraZeneca, Boehringer-Ingelheim, BMS, Eli Lilly, F. Hoffmann-La Roche, Ignyta, Merck Sharp and Dohme, Merck Serono, Novartis, Pfizer. Sara Manglaviti: advisory board for Italpharma; travel accommodation by MSD and Sanofi outside the submitted work. Mario Occhipinti: advosry board for BMS and personal fee by MSD. Laura Mazzeo: travel accomodation by Sanofi. Marta Brambilla: travel accomodation by Lilli and Leo Pharma, Teresa Beninato: travel accomodation by Lilli, MSD, BMS and Sanofi. The other authors report no conflict of interest.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)