Interim analysis of a phase II study of dose-modified FOLFIRINOX (mFOLFIRINOX) in locally advanced (LAPC) and metastatic pancreatic cancer (MPC).

Abstract

e15226 Background: Although FOLFIRINOX is superior to gemcitabine in MPC, the regimen is associated with significant toxicities (Conroy et al. N Engl J Med 2011;364:1817). In our prior retrospective analysis, efficacy was not compromised by dose attenuations of FOLFIRINOX (Gunturu et al. Med Oncol 2013;30:361). Based on this analysis, we are conducting a prospective, phase II, open-label study to evaluate the efficacy and tolerability of mFOLFIRINOX in pts with advanced pancreatic cancer (PC). Methods: Previously untreated pts with MPC or LAPC received mFOLFIRINOX with 25% dose reductions of irinotecan and bolus 5-FU given every two wks until progression, unacceptable toxicity, or surgical resection. All pts received prophylactic pegfilgrastim. FDG-PET scans were obtained at baseline and after 2 cycles. CAT scans were obtained after every 4 cycles. Toxicities and response rate (RR) were compared to historical data reported by Conroy. Results: 62 pts with ECOG PS ≤1 have been enrolled between 11/2011 and 12/2013, Pt characteristics: LAPC 27; MPC 35; median age 62 yrs (range 46-86); male 37. Median number of cycles was 8 (range 1-21). Grade 3/4 toxicities were: vomiting, peripheral sensory neuropathy (PSN) - 3.2%; ALT elevated, thromboembolism, febrile neutropenia - 4.8%; anemia - 6.4%; diarrhea, neutropenia - 16.2%; fatigue - 12.9%; thrombocytopenia - 11.3%. Neutropenia (p<0.0001) and vomiting (p=0.006) were significantly decreased. There was a nonsignificant trend toward a lower incidence of fatigue (p=0.05). Response by RECIST (CR+PR) in 29 evaluable pts with MPC was 31.4% (0 CR, 11 PR, 15 SD, 3 PD) and similar to historical data (31.6%; p 0.82). 9/21 evaluable pts with LAPC underwent resection (43%).16/43 pts evaluable for PET response had a >50% decrease in SUV(max)(37%). Conclusions: Findings from our interim analysis suggests that mFOLFIRINOX, given along with prophylactic pegfilgrastim is associated with a similar RR and improved tolerability compared to full dose FOLFIRINOX in advanced PC. In pts with LAPC, neoadjuvant FOLFIRINOX appears to have substantial activity with 43% of evaluable pts undergoing resection. Planned accrual has been completed. Interim OS and PFS will be reported. Clinical trial information: NCT01523457.