Anne Aarnink1, Jean David Fumet1,2,3,4,5, Laure Favier1, Caroline Truntzer2,3,5, Francois Ghiringhelli6,7,8,9,10. 1. Department of Medical Oncology, Center Georges François Leclerc, 1 rue du Professeur Marion, 21000, Dijon, France. 2. Research Platform in Biological Oncology, Dijon, France. 3. GIMI Genetic and Immunology Medical Institute, Dijon, France. 4. University of Burgundy-Franche Comté, Dijon, France. 5. UMR INSERM 1231, Dijon, France. 6. Department of Medical Oncology, Center Georges François Leclerc, 1 rue du Professeur Marion, 21000, Dijon, France. fghiringhelli@cgfl.fr. 7. Research Platform in Biological Oncology, Dijon, France. fghiringhelli@cgfl.fr. 8. GIMI Genetic and Immunology Medical Institute, Dijon, France. fghiringhelli@cgfl.fr. 9. University of Burgundy-Franche Comté, Dijon, France. fghiringhelli@cgfl.fr. 10. UMR INSERM 1231, Dijon, France. fghiringhelli@cgfl.fr.
Abstract
BACKGROUND: Checkpoint inhibitors (CKI) targeting PD-1 or PD-L1 are major therapies for the treatment of non-small cell lung cancer (NSCLC). Despite numerous studies of biological biomarkers, we currently lack a marker to predict CKI primary resistance. The aim of this study was to isolate clinical markers associated with the absence of efficacy of CKI used as monotherapy in NSCLC. METHODS: We conducted a retrospective analysis of 172 patients treated with anti-PD1 or anti-PDL1 monoclonal antibodies (mAb) for advanced NSCLC at the Dijon Cancer Center. Baseline characteristics were compared using the Chi squared test between responders and non-responders. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test for univariate analysis. Cox regression models were used to determine hazard ratios and 95% confidence intervals for progression-free survival (PFS) and overall survival (OS). RESULTS: Among 172 patients included, 149 (86.5%) received CKI after platinum chemotherapy. Response rate (RR) was 16%, median progression-free survival (PFS) was 2.5 months (95% CI 0.7-30 months) and median overall survival (OS) was 10 months (95% CI 0.7-46.8 months). By univariate analysis, WHO performance status ≥ 1, presence of bone, liver and pleuroperitoneal metastasis were associated with poor PFS and OS. Multivariate analysis showed that only pleuroperitoneal metastasis was independently associated with PFS and OS. Patients with pleuroperitoneal metastasis and WHO performance status ≥ 1 had a < 10% chance of yielding a benefit from CKI. CONCLUSIONS: Our data support the hypothesis that pleuroperitoneal metastasis is a major predictive factor affecting CKI efficacy in NSCLC patients and may be used to avoid CKI monotherapy for such patients.
BACKGROUND: Checkpoint inhibitors (CKI) targeting PD-1 or PD-L1 are major therapies for the treatment of non-small cell lung cancer (NSCLC). Despite numerous studies of biological biomarkers, we currently lack a marker to predict CKI primary resistance. The aim of this study was to isolate clinical markers associated with the absence of efficacy of CKI used as monotherapy in NSCLC. METHODS: We conducted a retrospective analysis of 172 patients treated with anti-PD1 or anti-PDL1 monoclonal antibodies (mAb) for advanced NSCLC at the Dijon Cancer Center. Baseline characteristics were compared using the Chi squared test between responders and non-responders. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test for univariate analysis. Cox regression models were used to determine hazard ratios and 95% confidence intervals for progression-free survival (PFS) and overall survival (OS). RESULTS: Among 172 patients included, 149 (86.5%) received CKI after platinum chemotherapy. Response rate (RR) was 16%, median progression-free survival (PFS) was 2.5 months (95% CI 0.7-30 months) and median overall survival (OS) was 10 months (95% CI 0.7-46.8 months). By univariate analysis, WHO performance status ≥ 1, presence of bone, liver and pleuroperitoneal metastasis were associated with poor PFS and OS. Multivariate analysis showed that only pleuroperitoneal metastasis was independently associated with PFS and OS. Patients with pleuroperitoneal metastasis and WHO performance status ≥ 1 had a < 10% chance of yielding a benefit from CKI. CONCLUSIONS: Our data support the hypothesis that pleuroperitoneal metastasis is a major predictive factor affecting CKI efficacy in NSCLCpatients and may be used to avoid CKI monotherapy for such patients.
Entities:
Keywords:
Biomarkers; Checkpoint inhibitors; Immunotherapy; Non-small cell lung cancer