1719P Predictive value of DNA repair gene alterations for the response to platinum-based chemotherapy and immunotherapy in advanced solid tumors patients: Results from a single center molecular screening program

Homologous recombination DNA repair deficiency is associated with sensitivity to platinum in certain cancer types, including breast, ovarian, pancreatic, and prostate. We aimed characterize the antitumor activity of platinum-based therapies patients (pts) unselected advanced solid tumors for who a gene alteration (DNA-RGA) was identified through tumor molecular screening program (TMSP). All comers pts from TMSP Institut Bergonié, Bordeaux, France, were reviewed. Each DNA-RGA classified as pathogenic (P), probably (PP), unknown pathogenecity (UP) according OncoKB and/or ClinVAR databases defined 3 groups. Between January 2018 May 2020, 662 screened. 199 found 121 (27.7%) pts. The most frequent mutations : ATM (N=40), POLE (N=23), BAP1 (N=19), BRCA2 (N=16), PMS2 (N=9), ATR MSH2 (N=8) BRCA1 (N=8). 96 received chemotherapy setting, mostly lung (N=28). Platinum carboplatin 46 (48%) No difference overall response rate (ORR) under regimen observed between (P,PP,UP) Median progression free survival (PFS) 8.4 months (IC95% 7 – 9.4). only predictor worst PFS Cox regression model existence P compared UP group: HR=2.11 (95%CI = 1.2 3.7), 0.0094. group had better 6-months P/PP 81% vs 60%, p=0.0382. 48/96 immune checkpoint inhibitor (ICI) alone or combination. Interestingly we trend an increased ORR ICI status 1/11, 5/16, 9/20 (p=0.14; Chi-2 test proportions: p=0.04) UP, PP respectively. same on 11, 44 50% groups respectively (p=0.37). impacted but not Though limited population size, this exploratory study paves way further investigations evaluting biomarkers ICI.