FOLFIRINOX until progression, FOLFIRINOX with maintenance treatment, or sequential treatment with gemcitabine and FOLFIRI.3 for first-line treatment of metastatic pancreatic cancer: A randomized phase II trial (PRODIGE 35-PANOPTIMOX).

4000 Background: Metastatic pancreatic cancer (mPC) still harbors a dismal prognosis (5-year overall survival [OS] <5%). Our previous trial (PRODIGE4-ACCORD11) has demonstrated the superiority of 6-month [m] chemotherapy with FOLFIRINOX over gemcitabine in terms of progression-free survival [PFS] (6.4 vs. 3.3 m; HR: 0.47; 95%CI: 0.37-0.59; p<0.001) and OS (11.1 vs. 6.8 m; HR: 0.57; 95%CI: 0.45-0.73; p<0.001), at the expense of higher toxicity, notably cumulative, often limiting, peripheral neuropathy with oxaliplatin. In this randomized Phase II trial, we aimed to assess an oxaliplatin ‘stop-and-go’ strategy and an alternative sequential strategy in mPC. Methods: Patients (pts) were randomized to receive either 6m FOLFIRINOX (arm A), 4m FOLFIRINOX followed by LV5FU2 maintenance treatment for controlled pts, and treatment reintroduction at disease progression (arm B), or a sequential treatment alternating gemcitabine and FOLFIRI.3 every 2m (arm C). The primary endpoint was to evaluate the 6m-PFS rate (H0: 30%, H1: 45%, Fleming design) in order to select the best therapeutic strategy for a future Phase III clinical trial. Results: Between Jan 2015 and Nov 2016, 273 pts (mean age: 63 years; range: 40-76) were enrolled (A: 91; B: 92; C: 90). The median durations of treatment were 5.1, 6.2, and 4.4 m in A, B, and C respectively. Grade 3/4 neurotoxicity occurred in 10% of pts in arm A and 19% of pts in arm B. Median ratio of oxaliplatin was 83% in A and 92% in B. 6m-PFS rates were 47% in A, 44% in B, and 34% in C. 4m objective response rates were 35% in A, 41% in B, and 17% in C. Median PFS was respectively 6.3, 5.7 and 4.5 m in A, B and C. Median OS was 10.1 in A, 11.2 in B and 7.3 m in C. The median duration of first maintenance therapy in B was 3.3 m (range: 0.03-22.6). Conclusions: Maintenance with LV5FU2 appears to be feasible and effective in patients with mPC controlled after 4m of induction chemotherapy with FOLFIRINOX. Severe neurotoxicity rate was higher in the maintenance therapy arm, likely because of higher cumulative oxaliplatin dose.1Conroy NEJM 2011. Clinical trial information: NCT02352337.