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1545P DNA damage repair (DDR) gene mutations (mut) are predictors of response to platinum-based chemotherapy in advanced pancreatic cancer (PC) patients (pts)

2020; Elsevier BV; Volume: 31; Linguagem: Inglês

10.1016/j.annonc.2020.08.2028

1569-8041

Helena Verdaguer, M. Guardiola, Francesco M. Mancuso, D.A. Acosta Eyzaguirre, Elvira Buxó, Jorge Hernando, M. Díez García, Berta Laquente, I. Baraibar Argota, Javier Ros, Alejandro García‐Álvarez, Judit Matito, Amber Martin, A. Sierra, G. Villacampa Javierre, Cristina Molero, Josep M. Miquel, Ana Vivancos, Rodrigo Dienstmann, T. Macarulla Mercadé,

Renal cell carcinoma treatment

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. 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 1st 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). 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 1st. line treatment. Prevalence of DDR mut are described in the table.Table:Overall population (n=48)Non Responders (n=18)Responders (n=30)Fisher Test P-valueFunctional BRCA1, BRCA2 or PALB28 (16.7%)08 (26.7%)0.018Any functional DDR16 (33.3%)3 (16.7%)13 (43.3%)0.068 Open table in a new tab 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). 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.