Article Text
Abstract
Introduction/Background Clinical benefit to immunotherapy (ICPI) has been limited to date in high-grade serous ovarian carcinoma (HGSOC), underpinning the necessity of better patient’s selection. Conversely, peripheral blood parameters such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) have been correlated to ICPI benefit in various malignancies. As such, the present ancillary study from the NEOPEMBROV/GINECO phase II trial (NCT03275506) assessed these parameters as predictive biomarkers of pembrolizumab (P) adjunction to standard chemotherapy (CT) and interval debulking surgery for advanced HGSOC.
Methodology 91 patients were enrolled in the trial (P+CT arm: 61; CT arm: 30). Optimal cut-off values for baseline NLR, PLR, and LMR regarding progression-free survival (PFS) in the P+CT arm were determined by ROC curves. Subsequently, a composite blood score (CBS) integrating these three biomarkers was evaluated.
Results Using ROC-based optimal cutoff values, we observed in P+CT arm a positive predictive impact of NLR ≤4 vs >4 (median PFS: 26.2 vs 17.0 months; hazard ratio (HR) 0.48 ; 95% confidence-interval (95CI) 0.25–0.89; p<0.05), PLR ≤250 vs >250 (median PFS: 26.0 vs 17.2 months; HR 0.49 ; 95CI 0.26–0.91; p<0.05) and LMR ≥2 vs <2 (median PFS: 25.8 versus 17.0 months; HR 0.47 ; 95CI 0.23–0.93; p<0.05). CBS, defined as the combination of NLR ≤4 + PLR ≤250 + LMR ≥2 in a given patient led to the following median PFS: 30.7 vs 15.1 months (HR 0.31; 0.16–0.60; CBS positive (n=33) and negative (n=28), respectively; p<0.0001). Interestingly, none of these biomarkers were associated with enhanced PFS in the CT arm.
Conclusion Our study reports that baseline NLR, PLR, LMR and CBS are promising predictive biomarkers of P+CT treatment efficacy in newly diagnosed HGSOC. These exploratory results will require to be further assessed and validated in larger cohorts of patients with HGSOC and treated with ICPI.
Disclosures Stanislas Quesada: no COI
Isabelle Ray-Coquard: GINECO President
Camille Schiffler: no COI
Aude-Marie Savoye: no COI
Marie-Ange Mouret-Reynier
Florence Joly: honoraria or consultations fees for AstraZeneca, GSK, Janssen, Ipsen, Clovis, Amgen, Astellas, MSD, BMS, Bayer
Olfa Derbel Miled: no COI
Elsa Kalbacher: honoraria or consultations fees for Astrazeneca, GSK, Sanofi, Roche, Seagen
Alejandra Martinez: honoraria or consultations fees for GSK
Marianne Leheurteur: travel grants from MSD
Jérôme Meunier: no COI
Mathilde Martinez: no COI
Nicolas Cloarec: no COI
Laurence Venat-Bouvet: no COI
Dominique Berton: no COI
Frédéric Selle: honoraria or consultations fees for GSK, AstraZeneca, MSD, Eisai
Pierre-Alexandre Just: honoraria or consultations fees for GSK and Roche
Guillaume Bataillon: Consulting/Advisory Board for GSK
Isabelle Treilleux: no COI
Olivia Le Saux: honoraria or consultations fees for GSK, Clovis, MSD