Correlation of early tumor shrinkage (ETS) and depth of response (DoR) with resectability in patients (pts) with unresectable locally advanced pancreatic cancer (LAPC) undergoing primary treatment with FOLFOXIRI.

Abstract

e15777 Background: FOLFIRINOX is a reasonable option in LAPC. GONO FOLFOXIRI has been shown to provide similar efficacy in advanced disease. ETS and DoR, emerging as relevant endpoints in colorectal cancer, have been rarely investigated in LAPC. Methods: Unresectable LAPC pts treated with FOLFOXIRI were identified. Computed tomography (CT) scan was performed every 8 weeks; after that, multidisciplinary team assessed resectability. ETS was defined as the reduction of ≥20% of target lesions’ diameters at first evaluation. DoR was the % of maximal tumor shrinkage at the nadir compared to baseline. Primary endpoint was the correlation of ETS and DoR with radical (R0) resection. Secondary endpoints were correlation of ETS and DoR with overall survival (OS) and progression-free survival (PFS). Radiologist was blinded to survival data. Survival curves were estimated using the Kaplan-Meier method. Log-rank and chi-square tests were applied. Results: Sixty pts were included. Median age was 62 years (range: 34-74), tumor location was head in 68% and body-tail in 32%. At a median follow-up of 26.9 months, response rate was 37%, median OS and PFS were 15.7 and 10.3 months, respectively. Thirty patients (50%) underwent R0 surgery after chemotherapy. Two pts died due to early surgical complication and were censored at the date of surgery for survival analyses. Among 55 evaluable pts, ETS was reached in 19 pts and median DoR was -17% (range: -65 to +100). A strong association between ETS (p = 0.0002) and DoR (p < 0.0001) with R0 resection was observed. In the overall population, ETS was significantly associated with better PFS (14.5 vs 9.4 months, p = 0.037), while no difference in OS was shown (p = 0.63). DoR was significantly associated both with PFS (13.6 vs 7.8 months, p = 0.014) and OS (19.8 vs 14.5 months, p = 0.047). Conclusions: FOLFOXIRI may allow achieving resectability in selected pts. ETS and DoR are significantly associated with R0 resection. Maximizing response with active regimens could be an effective strategy in LAPC. Further validation of ETS and DoR as surrogate endpoints in larger prospective series is required.