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.

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

Grossi, Francesco;
2022-01-01

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.
2022
2021
Early immune-related adverse events; Immune checkpoints inhibitors; Non-small cell lung cancer; Prediction; B7-H1 Antigen; Humans; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Retrospective Studies; Antineoplastic Agents, Immunological; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms
Russano, Marco; Cortellini, Alessio; Giusti, Raffaele; Russo, Alessandro; Zoratto, Federica; Rastelli, Francesca; Gelibter, Alain; Chiari, Rita; Nigro, Olga; De Tursi, Michele; Bracarda, Sergio; Gori, Stefania; Grossi, Francesco; Bersanelli, Melissa; Calvetti, Lorenzo; Di Noia, Vincenzo; Scartozzi, Mario; Di Maio, Massimo; Bossi, Paolo; Falcone, Alfredo; Citarella, Fabrizio; Pantano, Francesco; Ficorella, Corrado; Filetti, Marco; Adamo, Vincenzo; Veltri, Enzo; Pergolesi, Federica; Occhipinti, Mario Alberto; Nicolardi, Linda; Tuzi, Alessandro; Di Marino, Pietro; Macrini, Serena; Inno, Alessandro; Ghidini, Michele; Buti, Sebastiano; Aprile, Giuseppe; Lai, Eleonora; Audisio, Marco; Intagliata, Salvatore; Marconcini, Riccardo; Brocco, Davide; Porzio, Giampiero; Piras, Marta; Rijavec, Erika; Simionato, Francesca; Natoli, Clara; Tiseo, Marcello; Vincenzi, Bruno; Tonini, Giuseppe; Santini, Daniele
File in questo prodotto:
File Dimensione Formato  
Russano M - Cancer Immunol Immunother 2022.pdf

non disponibili

Tipologia: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 1.35 MB
Formato Adobe PDF
1.35 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2142215
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 8
social impact