1121P - Factors predicting overall survival (OS) and progression-free survival (PFS) in real-life: Classification and regression tree analysis of a 5-year (5Y) cohort follow-up study of advanced melanoma patients (pts) that have initiated pembrolizumab

Background

Factors predicting OS and PFS in anti-PD-1-treated melanoma pts are unknown in real-life pts, where brain metastasis or ECOG performance status >1 are frequent. Likewise, the prognostic value of AJCC staging (7^th and 8^th editions) remains unknown in this population.

Methods

HORIZON is a multicenter ambispective cohort of advanced melanoma pts who initiated pembrolizumab (2 mg/kg/3w) during the French Early Access Program (ATU, 5/2014 to 9/2015, CCTIRS #15.640) and were followed up to 5Y. Multivariate analyses first selected candidate variables among ECOG, serum LDH, N organs with metastasis <3 or ≥3, naïve vs non-naïve, brain or liver metastasis, AJCC7 and AJCC8 scores. All variables associated with OS and PFS were classified by classification and regression tree (CART); Kaplan-Meier analyses of OS and PFS were performed on identified pt groups, with multivariate Cox regressions (significance, p<0.05). Data cut-off: 18/11/2019.

Results

705 pts (161 with brain metastasis and 125 ECOG >1) were included in 41 centers. Based on CART analysis, with the AJCC7, a combination of ECOG status, serum LDH and AJCC7 score best predicted 1-, 2- and 3-Y OS, while ECOG and AJCC7 scores alone best predicted PFS. Using AJCC8, a combination of ECOG, serum LDH and AJCC8 score best fit OS, and a combination of ECOG, serum LDH, AJCC8 score, and the presence of liver metatasis best fit PFS. Brain metastatasis was not selected in any of the CART analyses. Using AJCC7, the best OS was observed in pts with ECOG ≤1 and an AJCC7 score M1A/B, and the worst in pts with ECOG >1 and high serum LDH (HR 9.2, 95%CI [6.4–13.3]). When using AJCC8, the best OS was observed in pts with ECOG ≤1, normal serum LDH and an AJCC score M1A/B and the worst in pts with ECOG >1 and an elevated serum LDH (HR 9.43, 95%CI [6.5–13.6]). Multivariate analyses, regression tree models and survival curves will be presented.

Conclusions

ECOG status was the main factor associated with OS and PFS, with an additional prognostic value provided by LDH serum levels and AJCC scores (both the 7^th and 8^th editions). We would like to thank to the entire RIC-Mel network team.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

MSD France.

Funding

MSD France.

Disclosure

P. Saiag: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck-Serono; 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 (institution): Array; Honoraria (self), Advisory/Consultancy: Sanofi/Regeneron. N. Meyer: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy: Roche; Advisory/Consultancy: Incyte. C. Dutriaux: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre. L. Verdoni: Shareholder/Stockholder/Stock options, Full/Part-time employment: MSD France. O. Morsli: Shareholder/Stockholder/Stock options, Full/Part-time employment: MSD France. A. Spampinato: Shareholder/Stockholder/Stock options, Full/Part-time employment: MSD France. L. Lattenist: Full/Part-time employment: ClinSearch. L. Mortier: 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 (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis. J-J. Grob: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Pfizer.