Efficacy and safety of programmed cell-death-protein-1 and its ligand inhibitors in pretreated patients with epidermal growth-factor receptor-mutated or anaplastic lymphoma kinase-translocated lung adenocarcinoma
Open Access
- 1 January 2020
- journal article
- research article
- Published by Wolters Kluwer Health in Medicine
- Vol. 99 (3) , e18726
Abstract
Immune-checkpoint inhibitor (ICI) efficacy in patients with non-small cell lung cancer (NSCLC) harboring molecular alterations remains poorly elucidated. This study was undertaken to determine ICI efficacy against epidermal growth-factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1)-mutated NSCLC patients in the real-world setting. In this retrospective, multicenter study on adults with ICI-treated EGFR-mutated or ALK- or ROS1-translated NSCLCs, we analyzed clinical characteristics and outcomes: ICI-treatment duration, and progression-free survival (PFS), objective response rate, duration of response, and overall survival (OS) from immunotherapy initiation. Fifty-one NSCLC patients (mean age, 58.0 years) were included from 20 French centers: 61% were never-smokers and 59% were women. Among them, 82% had EGFR-activating mutations, 16% ALK translocations, or 2% ROS1 translocations. Before ICI therapy, patients had received a median of 3 treatment lines (including tyrosine-kinase inhibitor). The median PFS was 2.1 (95% confidence interval [CI], 1.5–3.2) months for the entire cohort, 2.2 (95% CI, 1.4–3.2) for EGFR-mutated patients, and 2.4 (95% CI, 2.1–not reached) months for ALK-translocated patients. The median OS was 14.7 (95% CI, 12.1–19.2) months for the entire population and 13.9 (95% CI, 8.8–20.0) and 19.2 (95% CI, 13.1–not reached) months for EGFR-mutated and ALK-translocated patients, respectively. Seven (13.7%) patients were treated with ICI for >9 months. Toxicities were reported in 22% (11/51), including 8% (4/51) grade ≥3. In this real-world setting, analysis of ICI PFS against EGFR-mutated or ALK-translocated NSCLC patients appeared close to that observed in pretreated unselected NSCLC patients. The more promising OS probably linked to post-ICI treatments. Large prospective studies on these patient subsets are needed.Keywords
Funding Information
- GFPC (18/2)
This publication has 41 references indexed in Scilit:
- Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR MutationsJournal of Clinical Oncology, 2013
- Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin–paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002)Annals of Oncology, 2012
- Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trialThe Lancet Oncology, 2012
- Epidermal growth factor receptor‐tyrosine kinase inhibitor therapy is effective as first‐line treatment of advanced non‐small‐cell lung cancer with mutated EGFR: A meta‐analysis from six phase III randomized controlled trialsInternational Journal of Cancer, 2011
- Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 studyThe Lancet Oncology, 2011
- Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR InhibitorsScience Translational Medicine, 2011
- Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFRNew England Journal of Medicine, 2010
- Gefitinib or Carboplatin–Paclitaxel in Pulmonary AdenocarcinomaNew England Journal of Medicine, 2009
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal of Cancer, 2009
- EGFRMutation and Resistance of Non–Small-Cell Lung Cancer to GefitinibNew England Journal of Medicine, 2005