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. 2022 Apr;71(4):865-874.
doi: 10.1007/s00262-021-03045-9. Epub 2021 Aug 31.

Clinical outcomes of NSCLC patients experiencing early immune-related adverse events to PD-1/PD-L1 checkpoint inhibitors leading to treatment discontinuation

Marco Russano #  1 , Alessio Cortellini #  2 , Raffaele Giusti  3 , Alessandro Russo  4 , Federica Zoratto  5 , Francesca Rastelli  6 , Alain Gelibter  7 , Rita Chiari  8 , Olga Nigro  9 , Michele De Tursi  10 , Sergio Bracarda  11 , Stefania Gori  12 , Francesco Grossi  13 , Melissa Bersanelli  14   15 , Lorenzo Calvetti  16 , Vincenzo Di Noia  17 , Mario Scartozzi  18 , Massimo Di Maio  19 , Paolo Bossi  20 , Alfredo Falcone  21 , Fabrizio Citarella  22 , Francesco Pantano  1 , Corrado Ficorella  2 , Marco Filetti  3 , Vincenzo Adamo  4 , Enzo Veltri  5 , Federica Pergolesi  6 , Mario Alberto Occhipinti  7 , Linda Nicolardi  8 , Alessandro Tuzi  9 , Pietro Di Marino  10 , Serena Macrini  11 , Alessandro Inno  12 , Michele Ghidini  13 , Sebastiano Buti  14   15 , Giuseppe Aprile  16 , Eleonora Lai  18 , Marco Audisio  19 , Salvatore Intagliata  20 , Riccardo Marconcini  21 , Davide Brocco  23 , Giampiero Porzio  2 , Marta Piras  3 , Erika Rijavec  13 , Francesca Simionato  16 , Clara Natoli  10 , Marcello Tiseo  14   15 , Bruno Vincenzi  1 , Giuseppe Tonini  1 , Daniele Santini  1
Affiliations

Clinical outcomes of NSCLC patients experiencing early immune-related adverse events to PD-1/PD-L1 checkpoint inhibitors leading to treatment discontinuation

Marco Russano et al. Cancer Immunol Immunother. 2022 Apr.

Abstract

Background: The prognostic relevance of early immune-related adverse events (irAEs) in patients affected by non-small cell lung cancer (NSCLC) upon immunotherapy is not fully understood.

Methods: The Leading to Treatment Discontinuation cohort included 24 patients experiencing severe irAEs after one of two administrations of single anti-PD-1/PD-L1 in any line setting for metastatic NSCLC between November 2015 and June 2019. The control cohort was composed of 526 patients treated with single anti-PD-1/PD-L1 in any line setting with no severe irAE reported. The primary end points were median progression-free survival, overall survival, objective response rate, risk of progression of disease and risk of death. The correlation of clinic pathological features with early severe irAEs represented the secondary end point.

Results: Median PFS was 9.3 and 8.4 months, median OS was 12.0 months and 14.2 months at a median follow-up of 18.1 and 22.6 months in the LTD cohort and in the control cohort, respectively. The ORR was 40% (95% CI 17.2-78.8) in the LTD cohort and 32.7% (95% CI 27.8-38.2) in the control cohort. The risk of disease progression was higher in the LTD cohort (HR 2.52 [95% 1.10-5.78], P = .0288).

Conclusions: We found no survival benefit in LTD cohort compared to the control cohort. However, early and severe irAEs might underly an immune anti-tumor activation. We identified a significant association with first-line immune checkpoints inhibitors treatment and good PS. Further studies on risk prediction and management of serious and early irAEs in NSCLC patients are needed.

Keywords: Early immune-related adverse events; Immune checkpoints inhibitors; Non-small cell lung cancer; Prediction.

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Conflict of interest statement

Alessio Cortellini received speaker fees and grant consultancies from Roche, MSD, BMS, AstraZeneca, Novartis, Astellas. Marco Russano received honoraria for consultancy and scientific talks from Roche, BMS, MSD, Boehringer Ingelheim, AstraZeneca. Daniele Santini received speaker fees and grant consultancies from Janssen, Astellas, BMS, MSD, Pfizer, Boeringher Ingelheim, Roche, Eisai, Incyte, Novartis. Marcello Tiseo received speakers’ and consultants’ fee from AstraZeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre. Marcello Tiseo received institutional research grants from AstraZeneca, Boehringer Ingelheim. Sebastiano Buti received honoraria as a speaker at scientific events and advisory role by Bristol-Myers Squibb (BMS), Pfizer; MSD, Ipsen, Roche, Eli-Lilly, AstraZeneca, Pierre Fabre and Novartis.

Figures

Fig. 1
Fig. 1
Kaplan–Meier curves of PFS (A) and OS (B) in LTD cohort and control cohort
Fig. 2
Fig. 2
Kaplan–Meier curves of PFS (A) and OS (B) after random matching
See this image and copyright information in PMC

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