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

Marco Russano, Alessio Cortellini, Raffaele Giusti, Alessandro Russo, Federica Zoratto, Francesca Rastelli, Alain Gelibter, Rita Chiari, Olga Nigro, Michele De Tursi, Sergio Bracarda, Stefania Gori, Francesco Grossi, Melissa Bersanelli, Lorenzo Calvetti, Vincenzo Di Noia, Mario Scartozzi, Massimo Di Maio, Paolo Bossi, Alfredo FalconeFabrizio Citarella, Francesco Pantano, Corrado Ficorella, Marco Filetti, Vincenzo Adamo, Enzo Veltri, Federica Pergolesi, Mario Alberto Occhipinti, Linda Nicolardi, Alessandro Tuzi, Pietro Di Marino, Serena Macrini, Alessandro Inno, Michele Ghidini, Sebastiano Buti, Giuseppe Aprile, Eleonora Lai, Marco Audisio, Salvatore Intagliata, Riccardo Marconcini, Davide Brocco, Giampiero Porzio, Marta Piras, Erika Rijavec, Francesca Simionato, Clara Natoli, Marcello Tiseo, Bruno Vincenzi, Giuseppe Tonini, Daniele Santini

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalCancer Immunology, Immunotherapy
Publication statusAccepted/In press - 2021


  • Early immune-related adverse events
  • Immune checkpoints inhibitors
  • Non-small cell lung cancer
  • Prediction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research


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