Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with nivolumab: The Italian NSCLC expanded access program

Editta Baldini, Alice Lunghi, Enrico Cortesi, Daniele Turci, Diego Signorelli, Valeria Stati, Barbara Melotti, Biagio Ricciuti, Antonio Frassoldati, Giampiero Romano, Giovanni Luca Ceresoli, Alfonso Illiano, Francesco Verderame, Gianpiero Fasola, Enrico Ricevuto, Paolo Marchetti, Carmine Pinto, Giacomo Cartenì, Vieri Scotti, Carmelo TibaldiLuisa Fioretto, Diana Giannarelli

Research output: Contribution to journalArticle

Abstract

Objectives: The incidence of any and of severe-grade immune-related adverse events (irAEs) with second-line nivolumab monotherapy is 31–65 % and 2–5 % respectively. While potentially serious and even fatal, in the absence of an appropriate therapy, such events might be indicators of the activation of the immune system and, potentially, of efficacy. Materials and Methods: We collected the records of 1959 non-small-cell lung cancer (NSCLC) patients treated with nivolumab in the Italian expanded access program, and we registered the appearance of any and of severe grade irAEs. We retrospectively searched for correlations between toxicity and efficacy parameters by using Cox's regression analysis. Results: Overall, 342 (17.8%) patients developed an irAE of any grade. We observed that patients developing irAE of any grade achieved a significantly higher response rate (RR 27.2% vs 15.2%; p < 0.0001), disease control rate (DCR 60.5% vs 40.2%; p < 0.0001), median progression-free survival (mPFS 6.0 months [95% CI 4.9–7.1] vs 3.0 [95% CI: 2.8–3.2], p < 0.0001) and median overall survival (mOS 16.7 months [95% CI: 13.5–19.9] vs 9.4 [95% CI: 8.4–10.4], p < 0.00001) compared to patients who did not. At multivariate analysis the development of an irAE remained an independent indicator of nivolumab efficacy (HR 1.44 [95% CI: 1.22–1.71] p < 0.0001). Conclusions: This report, performed in Caucasian NSCLC patients, showed that the appearance of irAEs correlated with outcome.

Original languageEnglish
Pages (from-to)59-64
Number of pages6
JournalLung Cancer
Volume140
DOIs
Publication statusPublished - Feb 2020

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Non-Small Cell Lung Carcinoma
Disease-Free Survival
Immune System
Multivariate Analysis
Regression Analysis
nivolumab
Survival
Incidence
Therapeutics

Keywords

  • Immuno-Related adverse events
  • Nivolumab
  • Outcomes

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with nivolumab : The Italian NSCLC expanded access program. / Baldini, Editta; Lunghi, Alice; Cortesi, Enrico; Turci, Daniele; Signorelli, Diego; Stati, Valeria; Melotti, Barbara; Ricciuti, Biagio; Frassoldati, Antonio; Romano, Giampiero; Ceresoli, Giovanni Luca; Illiano, Alfonso; Verderame, Francesco; Fasola, Gianpiero; Ricevuto, Enrico; Marchetti, Paolo; Pinto, Carmine; Cartenì, Giacomo; Scotti, Vieri; Tibaldi, Carmelo; Fioretto, Luisa; Giannarelli, Diana.

In: Lung Cancer, Vol. 140, 02.2020, p. 59-64.

Research output: Contribution to journalArticle

Baldini, E, Lunghi, A, Cortesi, E, Turci, D, Signorelli, D, Stati, V, Melotti, B, Ricciuti, B, Frassoldati, A, Romano, G, Ceresoli, GL, Illiano, A, Verderame, F, Fasola, G, Ricevuto, E, Marchetti, P, Pinto, C, Cartenì, G, Scotti, V, Tibaldi, C, Fioretto, L & Giannarelli, D 2020, 'Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with nivolumab: The Italian NSCLC expanded access program', Lung Cancer, vol. 140, pp. 59-64. https://doi.org/10.1016/j.lungcan.2019.12.014
Baldini, Editta ; Lunghi, Alice ; Cortesi, Enrico ; Turci, Daniele ; Signorelli, Diego ; Stati, Valeria ; Melotti, Barbara ; Ricciuti, Biagio ; Frassoldati, Antonio ; Romano, Giampiero ; Ceresoli, Giovanni Luca ; Illiano, Alfonso ; Verderame, Francesco ; Fasola, Gianpiero ; Ricevuto, Enrico ; Marchetti, Paolo ; Pinto, Carmine ; Cartenì, Giacomo ; Scotti, Vieri ; Tibaldi, Carmelo ; Fioretto, Luisa ; Giannarelli, Diana. / Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with nivolumab : The Italian NSCLC expanded access program. In: Lung Cancer. 2020 ; Vol. 140. pp. 59-64.
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T1 - Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with nivolumab

T2 - The Italian NSCLC expanded access program

AU - Baldini, Editta

AU - Lunghi, Alice

AU - Cortesi, Enrico

AU - Turci, Daniele

AU - Signorelli, Diego

AU - Stati, Valeria

AU - Melotti, Barbara

AU - Ricciuti, Biagio

AU - Frassoldati, Antonio

AU - Romano, Giampiero

AU - Ceresoli, Giovanni Luca

AU - Illiano, Alfonso

AU - Verderame, Francesco

AU - Fasola, Gianpiero

AU - Ricevuto, Enrico

AU - Marchetti, Paolo

AU - Pinto, Carmine

AU - Cartenì, Giacomo

AU - Scotti, Vieri

AU - Tibaldi, Carmelo

AU - Fioretto, Luisa

AU - Giannarelli, Diana

PY - 2020/2

Y1 - 2020/2

N2 - Objectives: The incidence of any and of severe-grade immune-related adverse events (irAEs) with second-line nivolumab monotherapy is 31–65 % and 2–5 % respectively. While potentially serious and even fatal, in the absence of an appropriate therapy, such events might be indicators of the activation of the immune system and, potentially, of efficacy. Materials and Methods: We collected the records of 1959 non-small-cell lung cancer (NSCLC) patients treated with nivolumab in the Italian expanded access program, and we registered the appearance of any and of severe grade irAEs. We retrospectively searched for correlations between toxicity and efficacy parameters by using Cox's regression analysis. Results: Overall, 342 (17.8%) patients developed an irAE of any grade. We observed that patients developing irAE of any grade achieved a significantly higher response rate (RR 27.2% vs 15.2%; p < 0.0001), disease control rate (DCR 60.5% vs 40.2%; p < 0.0001), median progression-free survival (mPFS 6.0 months [95% CI 4.9–7.1] vs 3.0 [95% CI: 2.8–3.2], p < 0.0001) and median overall survival (mOS 16.7 months [95% CI: 13.5–19.9] vs 9.4 [95% CI: 8.4–10.4], p < 0.00001) compared to patients who did not. At multivariate analysis the development of an irAE remained an independent indicator of nivolumab efficacy (HR 1.44 [95% CI: 1.22–1.71] p < 0.0001). Conclusions: This report, performed in Caucasian NSCLC patients, showed that the appearance of irAEs correlated with outcome.

AB - Objectives: The incidence of any and of severe-grade immune-related adverse events (irAEs) with second-line nivolumab monotherapy is 31–65 % and 2–5 % respectively. While potentially serious and even fatal, in the absence of an appropriate therapy, such events might be indicators of the activation of the immune system and, potentially, of efficacy. Materials and Methods: We collected the records of 1959 non-small-cell lung cancer (NSCLC) patients treated with nivolumab in the Italian expanded access program, and we registered the appearance of any and of severe grade irAEs. We retrospectively searched for correlations between toxicity and efficacy parameters by using Cox's regression analysis. Results: Overall, 342 (17.8%) patients developed an irAE of any grade. We observed that patients developing irAE of any grade achieved a significantly higher response rate (RR 27.2% vs 15.2%; p < 0.0001), disease control rate (DCR 60.5% vs 40.2%; p < 0.0001), median progression-free survival (mPFS 6.0 months [95% CI 4.9–7.1] vs 3.0 [95% CI: 2.8–3.2], p < 0.0001) and median overall survival (mOS 16.7 months [95% CI: 13.5–19.9] vs 9.4 [95% CI: 8.4–10.4], p < 0.00001) compared to patients who did not. At multivariate analysis the development of an irAE remained an independent indicator of nivolumab efficacy (HR 1.44 [95% CI: 1.22–1.71] p < 0.0001). Conclusions: This report, performed in Caucasian NSCLC patients, showed that the appearance of irAEs correlated with outcome.

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