Background

Somatic DDR mut have been reported in close to 10% of PC samples. In this study we investigate their predictive value for response to platinum-based chemotherapy.

Methods

Case-control study with pts deriving response to oxaliplatin-based treatment (partial or complete response at any line) [n=30] versus no response (progression in first restaging at 1^st line) [n=18]. An in-house NGS panel test of 420 genes was performed on tumor samples. DDR mut were classified in 2 subgroups: (a) functional BRCA1, BRCA2 or PALB2; and (b) any functional DDR gene mut, including those in (a).

Results

48 pts were included, median ages was 54.5 years (30-74), 29 male, 26 were diagnosed with stage IV, 36 pts (75%) received FOLFIRINOX and 37 received platinum-based chemotherapy as 1^st. line treatment. Prevalence of DDR mut are described in the table. Table: 1545P

Among responders, 3 tumors had BRCA2 mt, 3 BRCA1, 2 ATM, and 1 each with BRCA2 + MSH2, PALB2, PMS2, MUYTH, RECQL4 + MDC1. Among non-responders 1 tumor each had ATM, FANCD2 and BLM. Median progression-free survival (PFS) with oxaliplatin-based chemotherapy in pts with BRCA1, BRCA2 or PALB2 mut tumors was 21.7 months (95% CI 12.3-NA); among those with any DDR mt was 12.3 months (95% CI 9.13-NA); while in pts whose tumors had no DDR mut was 6.4 months (95% CI 3.07-13)(Log-rank P-value = 0.02 comparison subgroup [a] vs. others; P-value = 0.1 subgroup [b] vs. others).

Conclusions

The subgroup of pts with PC tumors harboring somatic DDR gene mut, particularly functional BRCA1, BRCA2 or PALB2, have higher response rate and longer PFS with oxaplatin-based chemotherapy.

Legal entity responsible for the study

Vall d'Hebron Institute of Oncology.

Funding

AstraZeneca.

Disclosure

H. Verdaguer: Advisory/Consultancy: Ipsen. T. Macarulla Mercadé: Advisory/Consultancy: Celgene; Advisory/Consultancy: Baxter; Advisory/Consultancy: Eisai; Advisory/Consultancy: Incyte; Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Servier; Advisory/Consultancy: Lilly; Advisory/Consultancy: QED therapeutics; Advisory/Consultancy: Servier. All other authors have declared no conflicts of interest.