Italian Nivolumab Expanded Access Program in Nonsquamous Non–Small Cell Lung Cancer Patients: Results in Never-Smokers and EGFR-Mutant Patients

Marina Chiara Garassino, Alain Jonathan Gelibter, Francesco Grossi, Rita Chiari, Hector Soto Parra, Stefano Cascinu, Francesco Cognetti, Daniele Turci, Livio Blasi, Carmelo Bengala, Enrico Mini, Editta Baldini, Silvia Quadrini, Giovanni Luca Ceresoli, Paola Antonelli, Enrico Vasile, Carmine Pinto, Gianpiero Fasola, Domenico Galetta, Marianna MacerelliDiana Giannarelli, Giuseppe Lo Russo, Filippo de Marinis

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Introduction: Nivolumab is the first checkpoint inhibitor approved for the treatment of nonsquamous NSCLC. We report results from the nivolumab Italian expanded access program focusing on never-smokers and patients with EGFR-mutant nonsqamous NSCLC. Methods: Nivolumab (3 mg/kg intravenously every 2 weeks) was administered upon physicians’ request to patients who had relapsed after one or more prior systemic treatments for stage IIIB/IV nonsquamous NSCLC. Efficacy and safety were evaluated in patients who received at least one dose of nivolumab. Results: Of 1588 patients with nonsquamous NSCLC, 305 (19.2%) were never-smokers. EGFR status was available for 1395 patients. Of the 102 patients (6.4%) with EGFR mutation–positive tumors, 51 (50%) were never-smokers. The objective response rate was significantly higher in patients with wild-type EGFR than patients with EGFR-mutant tumors (19.6% versus 8.8% [p = 0.007]), in former and current smokers than in never-smokers (21.5% versus 9.2% [p = 0.0001]), and in never-smokers with wild-type EGFR than in never-smokers with mutant EGFR (11.0% versus 1.9% [p = 0.04]). There was no significant difference in objective response rate between smokers with wild-type EGFR and smokers with mutant EGFR (22.0% versus 20.6%). There was no statistically significant difference in median progression-free survival or in median overall survival. The median overall survival times were 11 months in patients with EGFR wild-type tumors versus 8.3 months in patients with EGFR-mutant tumors, 11.6 months in smokers versus 10.0 months in never-smokers, 11.0 months in never-smokers with EGFR wild-type tumors versus 5.6 months in never-smokers with EGFR-mutant tumors, and 14.1 months in smokers with EGFR-mutant tumors versus 11.3 months in smokers with EGFR wild-type tumors. Conclusions: The data on the Italian expanded access program in populations with nonsquamous NSCLC suggest that subgroups of patients could benefit differently from nivolumab according to their EGFR mutational status and smoking habits. These results warrant further investigation.

Original languageEnglish
Pages (from-to)1146-1155
Number of pages10
JournalJournal of Thoracic Oncology
Volume13
Issue number8
DOIs
Publication statusPublished - Aug 1 2018

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Non-Small Cell Lung Carcinoma
Neoplasms
nivolumab
Population Control
Survival
Disease-Free Survival
Habits
Smoking
Physicians
Safety

Keywords

  • EGFR positive
  • Expanded access program
  • Never-smokers
  • nivolumab
  • Nonsquamous non–small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Italian Nivolumab Expanded Access Program in Nonsquamous Non–Small Cell Lung Cancer Patients : Results in Never-Smokers and EGFR-Mutant Patients. / Garassino, Marina Chiara; Gelibter, Alain Jonathan; Grossi, Francesco; Chiari, Rita; Soto Parra, Hector; Cascinu, Stefano; Cognetti, Francesco; Turci, Daniele; Blasi, Livio; Bengala, Carmelo; Mini, Enrico; Baldini, Editta; Quadrini, Silvia; Ceresoli, Giovanni Luca; Antonelli, Paola; Vasile, Enrico; Pinto, Carmine; Fasola, Gianpiero; Galetta, Domenico; Macerelli, Marianna; Giannarelli, Diana; Lo Russo, Giuseppe; de Marinis, Filippo.

In: Journal of Thoracic Oncology, Vol. 13, No. 8, 01.08.2018, p. 1146-1155.

Research output: Contribution to journalArticle

Garassino, MC, Gelibter, AJ, Grossi, F, Chiari, R, Soto Parra, H, Cascinu, S, Cognetti, F, Turci, D, Blasi, L, Bengala, C, Mini, E, Baldini, E, Quadrini, S, Ceresoli, GL, Antonelli, P, Vasile, E, Pinto, C, Fasola, G, Galetta, D, Macerelli, M, Giannarelli, D, Lo Russo, G & de Marinis, F 2018, 'Italian Nivolumab Expanded Access Program in Nonsquamous Non–Small Cell Lung Cancer Patients: Results in Never-Smokers and EGFR-Mutant Patients', Journal of Thoracic Oncology, vol. 13, no. 8, pp. 1146-1155. https://doi.org/10.1016/j.jtho.2018.04.025
Garassino, Marina Chiara ; Gelibter, Alain Jonathan ; Grossi, Francesco ; Chiari, Rita ; Soto Parra, Hector ; Cascinu, Stefano ; Cognetti, Francesco ; Turci, Daniele ; Blasi, Livio ; Bengala, Carmelo ; Mini, Enrico ; Baldini, Editta ; Quadrini, Silvia ; Ceresoli, Giovanni Luca ; Antonelli, Paola ; Vasile, Enrico ; Pinto, Carmine ; Fasola, Gianpiero ; Galetta, Domenico ; Macerelli, Marianna ; Giannarelli, Diana ; Lo Russo, Giuseppe ; de Marinis, Filippo. / Italian Nivolumab Expanded Access Program in Nonsquamous Non–Small Cell Lung Cancer Patients : Results in Never-Smokers and EGFR-Mutant Patients. In: Journal of Thoracic Oncology. 2018 ; Vol. 13, No. 8. pp. 1146-1155.
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abstract = "Introduction: Nivolumab is the first checkpoint inhibitor approved for the treatment of nonsquamous NSCLC. We report results from the nivolumab Italian expanded access program focusing on never-smokers and patients with EGFR-mutant nonsqamous NSCLC. Methods: Nivolumab (3 mg/kg intravenously every 2 weeks) was administered upon physicians’ request to patients who had relapsed after one or more prior systemic treatments for stage IIIB/IV nonsquamous NSCLC. Efficacy and safety were evaluated in patients who received at least one dose of nivolumab. Results: Of 1588 patients with nonsquamous NSCLC, 305 (19.2{\%}) were never-smokers. EGFR status was available for 1395 patients. Of the 102 patients (6.4{\%}) with EGFR mutation–positive tumors, 51 (50{\%}) were never-smokers. The objective response rate was significantly higher in patients with wild-type EGFR than patients with EGFR-mutant tumors (19.6{\%} versus 8.8{\%} [p = 0.007]), in former and current smokers than in never-smokers (21.5{\%} versus 9.2{\%} [p = 0.0001]), and in never-smokers with wild-type EGFR than in never-smokers with mutant EGFR (11.0{\%} versus 1.9{\%} [p = 0.04]). There was no significant difference in objective response rate between smokers with wild-type EGFR and smokers with mutant EGFR (22.0{\%} versus 20.6{\%}). There was no statistically significant difference in median progression-free survival or in median overall survival. The median overall survival times were 11 months in patients with EGFR wild-type tumors versus 8.3 months in patients with EGFR-mutant tumors, 11.6 months in smokers versus 10.0 months in never-smokers, 11.0 months in never-smokers with EGFR wild-type tumors versus 5.6 months in never-smokers with EGFR-mutant tumors, and 14.1 months in smokers with EGFR-mutant tumors versus 11.3 months in smokers with EGFR wild-type tumors. Conclusions: The data on the Italian expanded access program in populations with nonsquamous NSCLC suggest that subgroups of patients could benefit differently from nivolumab according to their EGFR mutational status and smoking habits. These results warrant further investigation.",
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T1 - Italian Nivolumab Expanded Access Program in Nonsquamous Non–Small Cell Lung Cancer Patients

T2 - Results in Never-Smokers and EGFR-Mutant Patients

AU - Garassino, Marina Chiara

AU - Gelibter, Alain Jonathan

AU - Grossi, Francesco

AU - Chiari, Rita

AU - Soto Parra, Hector

AU - Cascinu, Stefano

AU - Cognetti, Francesco

AU - Turci, Daniele

AU - Blasi, Livio

AU - Bengala, Carmelo

AU - Mini, Enrico

AU - Baldini, Editta

AU - Quadrini, Silvia

AU - Ceresoli, Giovanni Luca

AU - Antonelli, Paola

AU - Vasile, Enrico

AU - Pinto, Carmine

AU - Fasola, Gianpiero

AU - Galetta, Domenico

AU - Macerelli, Marianna

AU - Giannarelli, Diana

AU - Lo Russo, Giuseppe

AU - de Marinis, Filippo

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Introduction: Nivolumab is the first checkpoint inhibitor approved for the treatment of nonsquamous NSCLC. We report results from the nivolumab Italian expanded access program focusing on never-smokers and patients with EGFR-mutant nonsqamous NSCLC. Methods: Nivolumab (3 mg/kg intravenously every 2 weeks) was administered upon physicians’ request to patients who had relapsed after one or more prior systemic treatments for stage IIIB/IV nonsquamous NSCLC. Efficacy and safety were evaluated in patients who received at least one dose of nivolumab. Results: Of 1588 patients with nonsquamous NSCLC, 305 (19.2%) were never-smokers. EGFR status was available for 1395 patients. Of the 102 patients (6.4%) with EGFR mutation–positive tumors, 51 (50%) were never-smokers. The objective response rate was significantly higher in patients with wild-type EGFR than patients with EGFR-mutant tumors (19.6% versus 8.8% [p = 0.007]), in former and current smokers than in never-smokers (21.5% versus 9.2% [p = 0.0001]), and in never-smokers with wild-type EGFR than in never-smokers with mutant EGFR (11.0% versus 1.9% [p = 0.04]). There was no significant difference in objective response rate between smokers with wild-type EGFR and smokers with mutant EGFR (22.0% versus 20.6%). There was no statistically significant difference in median progression-free survival or in median overall survival. The median overall survival times were 11 months in patients with EGFR wild-type tumors versus 8.3 months in patients with EGFR-mutant tumors, 11.6 months in smokers versus 10.0 months in never-smokers, 11.0 months in never-smokers with EGFR wild-type tumors versus 5.6 months in never-smokers with EGFR-mutant tumors, and 14.1 months in smokers with EGFR-mutant tumors versus 11.3 months in smokers with EGFR wild-type tumors. Conclusions: The data on the Italian expanded access program in populations with nonsquamous NSCLC suggest that subgroups of patients could benefit differently from nivolumab according to their EGFR mutational status and smoking habits. These results warrant further investigation.

AB - Introduction: Nivolumab is the first checkpoint inhibitor approved for the treatment of nonsquamous NSCLC. We report results from the nivolumab Italian expanded access program focusing on never-smokers and patients with EGFR-mutant nonsqamous NSCLC. Methods: Nivolumab (3 mg/kg intravenously every 2 weeks) was administered upon physicians’ request to patients who had relapsed after one or more prior systemic treatments for stage IIIB/IV nonsquamous NSCLC. Efficacy and safety were evaluated in patients who received at least one dose of nivolumab. Results: Of 1588 patients with nonsquamous NSCLC, 305 (19.2%) were never-smokers. EGFR status was available for 1395 patients. Of the 102 patients (6.4%) with EGFR mutation–positive tumors, 51 (50%) were never-smokers. The objective response rate was significantly higher in patients with wild-type EGFR than patients with EGFR-mutant tumors (19.6% versus 8.8% [p = 0.007]), in former and current smokers than in never-smokers (21.5% versus 9.2% [p = 0.0001]), and in never-smokers with wild-type EGFR than in never-smokers with mutant EGFR (11.0% versus 1.9% [p = 0.04]). There was no significant difference in objective response rate between smokers with wild-type EGFR and smokers with mutant EGFR (22.0% versus 20.6%). There was no statistically significant difference in median progression-free survival or in median overall survival. The median overall survival times were 11 months in patients with EGFR wild-type tumors versus 8.3 months in patients with EGFR-mutant tumors, 11.6 months in smokers versus 10.0 months in never-smokers, 11.0 months in never-smokers with EGFR wild-type tumors versus 5.6 months in never-smokers with EGFR-mutant tumors, and 14.1 months in smokers with EGFR-mutant tumors versus 11.3 months in smokers with EGFR wild-type tumors. Conclusions: The data on the Italian expanded access program in populations with nonsquamous NSCLC suggest that subgroups of patients could benefit differently from nivolumab according to their EGFR mutational status and smoking habits. These results warrant further investigation.

KW - EGFR positive

KW - Expanded access program

KW - Never-smokers

KW - nivolumab

KW - Nonsquamous non–small cell lung cancer

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