Arnaud Jeanson1, Pascale Tomasini1, Maxime Souquet-Bressand2, Nicolas Brandone3, Mohamed Boucekine4, Mathieu Grangeon2, Solène Chaleat2, Natalyia Khobta5, Julie Milia6, Laurent Mhanna6, Laurent Greillier1, Julie Biemar2, Isabelle Nanni7, L'houcine Ouafik8, Stéphane Garcia3, Julien Mazières6, Fabrice Barlesi9, Céline Mascaux1. 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, Marseille, 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, 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 University, APHM, CHU Nord, Service de Transfert d'Oncologie Biologique, Marseille, France. 8. Aix-Marseille University, APHM, CHU Nord, Service de Transfert d'Oncologie Biologique, Marseille, France; Aix-Marseille University, CNRS, INP, Neurophysiopathology Institute, 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, Marseille, France. Electronic address: fabrice.barlesi@ap-hm.fr.
Abstract
INTRODUCTION: KRAS mutation is the most frequent molecular alteration found in advanced NSCLC; it 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 (ICIs), and data about its efficacy in patients with KRAS-mutant NSCLC are discordant. This study assessed the routine efficacy of ICIs in advanced KRAS-mutant NSCLC. METHODS: In this retrospective study, clinical data were extracted from the medical records of patients with advanced NSCLC treated with ICIs and with available molecular analysis between April 2013 and June 2017. Analysis of programmed death ligand 1 (PD-L1) expression was performed if exploitable tumor material was available. RESULTS: A total of 282 patients with ICI-treated (in the first line or more) advanced NSCLC (all histological subgroups) who were treated with ICIs (anti-programmed death 1, anti-PD-L1, or anti-cytotoxic T-lymphocyte associated protein 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 of 1% or more and 50%, respectively (49.5% and 21.2%, respectively, in the case of the 85 patients with KRAS-mutant NSCLC). No significant difference was seen in terms of objective response rates, progression-free survival, or overall survival between KRAS-mutant NSCLC and other NSCLC. No significant differences in overall survival or progression-free survival were observed between the major KRAS mutation subtypes (G12A, G12C, G12D, G12V, and G13C). In KRAS-mutant NSCLC, unlike in non-KRAS-mutant NSCLC, the efficacy of ICIs is consistently higher, even though not statistically significant, for patients with PD-L1 expression in 1% or more of tumor cells than for those with PD-L1 expression in less than 1% of tumor cells, and this finding is especially true when PD-L1 expression is high (PD-L1 expression ≥50%). CONCLUSION: For patients with KRAS-mutant NSCLC (all mutational subtypes), the efficacy of ICI is similar to that for patients with other types of NSCLC. PD-L1 expression seems to be more relevant for predicting the efficacy of ICIs in KRAS-mutant NSCLC than it is in other types of NSCLC.
INTRODUCTION:KRAS mutation is the most frequent molecular alteration found in advanced NSCLC; it 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 (ICIs), and data about its efficacy in patients with KRAS-mutant NSCLC are discordant. This study assessed the routine efficacy of ICIs in advanced KRAS-mutant NSCLC. METHODS: In this retrospective study, clinical data were extracted from the medical records of patients with advanced NSCLC treated with ICIs and with available molecular analysis between April 2013 and June 2017. Analysis of programmed death ligand 1 (PD-L1) expression was performed if exploitable tumor material was available. RESULTS: A total of 282 patients with ICI-treated (in the first line or more) advanced NSCLC (all histological subgroups) who were treated with ICIs (anti-programmed death 1, anti-PD-L1, or anti-cytotoxic T-lymphocyte associated protein 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 of 1% or more and 50%, respectively (49.5% and 21.2%, respectively, in the case of the 85 patients with KRAS-mutant NSCLC). No significant difference was seen in terms of objective response rates, progression-free survival, or overall survival between KRAS-mutant NSCLC and other NSCLC. No significant differences in overall survival or progression-free survival were observed between the major KRAS mutation subtypes (G12A, G12C, G12D, G12V, and G13C). In KRAS-mutant NSCLC, unlike in non-KRAS-mutant NSCLC, the efficacy of ICIs is consistently higher, even though not statistically significant, for patients with PD-L1 expression in 1% or more of tumor cells than for those with PD-L1 expression in less than 1% of tumor cells, and this finding is especially true when PD-L1 expression is high (PD-L1 expression ≥50%). CONCLUSION: For patients with KRAS-mutant NSCLC (all mutational subtypes), the efficacy of ICI is similar to that for patients with other types of NSCLC. PD-L1 expression seems to be more relevant for predicting the efficacy of ICIs in KRAS-mutant NSCLC than it is in other types of NSCLC.
Authors: Kathryn C Arbour; Hira Rizvi; Andrew J Plodkowski; Matthew D Hellmann; Andrea Knezevic; Glenn Heller; Helena A Yu; Marc Ladanyi; Mark G Kris; Maria E Arcila; Charles M Rudin; Piro Lito; Gregory J Riely Journal: Clin Cancer Res Date: 2021-02-08 Impact factor: 12.531
Authors: Emil Lou; Joanne Xiu; Yasmine Baca; Andrew C Nelson; Benjamin A Weinberg; Muhammad Shaalan Beg; Mohamed E Salem; Heinz-Josef Lenz; Philip Philip; Wafik S El-Deiry; W Michael Korn Journal: Cells Date: 2021-05-21 Impact factor: 6.600
Authors: David M Briere; Shuai Li; Andrew Calinisan; Niranjan Sudhakar; Ruth Aranda; Lauren Hargis; David H Peng; Jiehui Deng; Lars D Engstrom; Jill Hallin; Sole Gatto; Julio Fernandez-Banet; Adam Pavlicek; Kwok-Kin Wong; James G Christensen; Peter Olson Journal: Mol Cancer Ther Date: 2021-03-15 Impact factor: 6.009