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DNA damage repair (DDR) gene mutations (mut) are predictors of response to platinum-based chemotherapy in advanced pancreatic cancer (PC) patients (pts).

2020; Lippincott Williams & Wilkins; Volume: 38; Issue: 15_suppl Linguagem: Inglês

10.1200/jco.2020.38.15_suppl.e16805

1527-7755

Helena Verdaguer, Magda Guardiola-Fernandez, Francesco M. Mancuso, Daniel Acosta, Elvira Buxó, Jorge Hernando, Marc Díez, Berta Laquente, Iosune Baraibar, Javier Ros, Alejandro Garcia, Judit Matito, Ágatha Martín, Alexandre Sierra, Guillermo Villacampa, Cristina Molero, Josep M. Miquel, Ana Vivancos, Rodrigo Dienstmann, Teresa Macarulla,

Genetic factors in colorectal cancer

e16805 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. 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 whit tumors harboring DDR gene mut, particularly functional BRCA1, BRCA2 or PALB2, have higher response rate and longer PFS with oxaplatin-based chemotherapy. [Table: see text]