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J Thorac Oncol. 2019 Feb 6. pii: S1556-0864(19)30040-1. doi: 10.1016/j.jtho.2019.01.011. [Epub ahead of print]

Brief report: efficacy of immune checkpoint inhibitors in KRAS-mutant Non-small cell lung cancer (NSCLC).

Author information

1
Aix Marseille University; Assistance Publique Hôpitaux de Marseille. Department of Multidisciplinary Oncology and Therapeutic Innovations. Marseille, France; Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm UMR1068, CNRS UMR7258, France.
2
Aix Marseille University; Assistance Publique Hôpitaux de Marseille. Department of Multidisciplinary Oncology and Therapeutic Innovations. Marseille, France.
3
Department of pathology, Assistance Publique-Hôpitaux de Marseille (AP-HM), Aix-Marseille Université, Marseille, France.
4
EA 3279 - Public Health, Chronic Diseases and Quality of Life - Research Unit, Aix-Marseille University, 13005, Marseille, France.
5
Aix Marseille University; Assistance Publique Hôpitaux de Marseille. Department of Multidisciplinary Oncology and Therapeutic Innovations. Marseille, France; Centre Hospitalier Departemental de Castellucio, Oncology department, Ajaccio, France.
6
Department of Pulmonology, Hôpital Larrey, Centre Hospitalier Universitaire, Paul Sabatier University, Toulouse, France.
7
Aix-Marseille Univ, APHM, CHU Nord, Service de Transfert d'Oncologie Biologique, Marseille, France.
8
Aix-Marseille Univ, APHM, CHU Nord, Service de Transfert d'Oncologie Biologique, Marseille, France; Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, Marseille, France.
9
Aix Marseille University; Assistance Publique Hôpitaux de Marseille. Department of Multidisciplinary Oncology and Therapeutic Innovations. Marseille, France; Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm UMR1068, CNRS UMR7258, France. Electronic address: fabrice.barlesi@ap-hm.fr.

Abstract

INTRODUCTION:

KRAS mutation (KRASm) is the most frequent molecular alteration found in advanced non-small cell lung cancer (NSCLC), is associated with a poor prognosis, without available targeted therapy. Treatment options for NSCLC have been recently enriched by the development of immune checkpoint inhibitors (ICI), and data about its efficacy in patients with KRASm NSCLC are discordant. This study assessed the routine efficacy of ICI in advanced KRASm NSCLC.

METHODS:

In this retrospective study, clinical data were extracted from the medical records of patients with advanced NSCLC treated with ICI and with available molecular analysis between April 2013 and June 2017. Analysis of PD-L1 expression was performed if exploitable tumor material was available.

RESULTS:

A total of 282 ICI-treated (in first line or more) advanced NSCLC (all histological subgroups) patients who were treated with ICI (anti-PD-1, anti PD-L1 or anti-CTLA-4 antibodies), including 162 (57.4%) with KRAS mutation, 27 (9.6%) with other mutations and 93 (33%) with a wild-type phenotype, were identified. PD-L1 analysis was available for 128 patients (45.4%), of whom 45.3% and 19.5% had PD-L1 expression ≥ 1% and 50%, respectively (49.5% and 21.2% respectively concerning 85 KRASm NSCLC patients). No significant difference was seen in terms of objective response rates (ORR), progression free survival (PFS) and overall survival (OS) between KRASm NSCLC and other NSCLC. No significant differences in OS or PFS were observed between the major KRAS mutation subtypes (G12A, G12C, G12D, G12V, and G13C). In KRASm NSCLC, unlike in non-KRASm NSCLC, the efficacy of ICI is consistently higher, eventhough not statistically significant, for patients with PD-L1 expression in ≥ 1% of tumor cells than for those with PD-L1 expression in < 1% of tumor cells, and this finding is especially true when PD-L1 expression is high (PD-L1 expression ≥ 50%).

DISCUSSION:

For patients with KRASm NSCLC (all mutational subtypes), the efficacy of ICI is similar to that of patients with other types of NSCLC. PD-L1 expression seems to be more relevant for predicting the efficacy of ICI in KRASm NSCLC than it is in other types of NSCLC.

KEYWORDS:

KRAS mutation; NSCLC; PD-L1 expression; immunotherapy

PMID:
30738221
DOI:
10.1016/j.jtho.2019.01.011

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