Abstract 1113P
Background
Anti-PD1 (Nivolumab, Pembrolizumab, APD) treatment (monotherapy or combination) efficacy is largely documented in advanced melanoma (AM) patients, as well as classical prognostic factors for longer survival. This study investigates 1- and 2-years mortality prediction in real world AM patients (rwAM), according to the most associated prognostic factors.
Methods
Clinical characteristics were collected from MelBase, a French multicentric biobank prospectively enrolling unresectable stage III or IV melanoma (26 centers, >1900 patients, NCT02828202). Data from 793 patients treated by APD in monotherapy (47% in 1st line in May 2019) were collected. Data were analyzed to develop a risk prediction model for 1- and 2-years overall survival (OS) in rwAM patients, using Random Forests. Performance was expressed in terms of calibration and discrimination (c-statistic). Model internal validation was performed by computing out-of-bag prediction error of Random Forests.
Results
Median age was 65 years, 92% of patients were ECOG 0-1, 36% BRAF mutated, 37% had elevated LDH, 55% were M1c (AJCC 7th edition), 26% had hepatic metastases and 41% had more than 3 metastatic organ sites (MOS). Among the 793 patients, 41% were treatef by nivolumab and 59% by pembrolizumab.
Median follow-up was 14 months (Q1-Q3 6-25) and median OS 19 months (95%CI 17 -24). The mortality risk score we developed used LDH, ECOG, BRAF, >3 MOS and the presence of hepatic metastasis at treatment initiation. It showed a fair discrimination, with a C statistic of 0.73 (95% CI 0.72-0.75) for 1-yr OS and 0.71 (0.70-0.74) for 2-yr OS. Out-of-bag prediction error was low, with values of 0.05 for 1-yr OS and 0.06 for 2-yr OS.
Model recalibration was necessary, due to overestimation of low mortality. After log transformation, the calibration curves indicated that the model was well calibrated and no deviation from the reference line.
Conclusions
This study predicts medium term survival (12, 24 months) according to baseline characteristics for rwAM patients treated by APD1 in monotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
AP-HP DRCI.
Funding
French National Cancer Institute (INCa), BMS, MSD, Novartis, Roche.
Disclosure
S. Dalle: Shareholder/Stockholder/Stock options, Full/Part-time employment: Sanofi; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Travel/Accommodation/Expenses: Pierre Fabre. L. Mortier: Travel/Accommodation/Expenses: Roche/Genentech; Honoraria (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Research grant/Funding (institution): MSD Oncology; Research grant/Funding (institution): Pierre Fabre; Travel/Accommodation/Expenses: Novartis. C. Dutriaux: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre. O. Dereure: Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: LeoPharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Recordati Rare Diseases; Advisory/Consultancy: Kyowa Kirin. S. Dalac: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy: PFO. D. Legoupil: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Travel/Accommodation/Expenses: MSD Brazil; Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre. J. De Quatrebarbes: Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Janssen-Cilag; Travel/Accommodation/Expenses: BMS Brazil; Travel/Accommodation/Expenses: MSD Oncology. H. Montaudié: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): LeoPharma. J.P. Arnault: Honoraria (self): BMS. P. Saiag: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck-Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Array; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy: Regeneron. E. Maubec: Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy: BMS; Travel/Accommodation/Expenses: MSD Oncology. T. Lesimple: Advisory/Consultancy: MSD; Advisory/Consultancy: Pierre Fabre; Research grant/Funding (self): Roche. C. Lebbé: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Sanofi; Honoraria (self): Pierre Fabre; Honoraria (self): Pfizer; Honoraria (self): Incyte. All other authors have declared no conflicts of interest.