Oxaliplatin stop-and-go strategy provides similar PFS, OS vs 1st-line SoC in pancreatic cancer

An oxaliplatin stop-and-go strategy of maintenance treatment with leucovorin plus fluorouracil in patients with metastatic pancreatic cancer controlled after 4 months of standard first-line fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) provides comparable progression-free survival (PFS) and overall survival (OS) vs 6 months of FOLFIRINOX, results of the phase II PANOPTIMOX-PRODIGE 35 trial have shown.

Although FOLFIRINOX is the standard-of-care (SoC) first-line chemotherapy for patients with metastatic pancreatic cancer, oxaliplatin-related neurotoxicity is a factor limiting its use. In the PANOPTIMOX-PRODIGE 35 trial, researchers evaluated an oxaliplatin stop-and-go strategy comprising 4 months of FOLFIRINOX followed by maintenance treatment with leucovorin plus fluorouracil for patients with controlled disease, as well as a sequential strategy alternating treatment with gemcitabine and fluorouracil, leucovorin, and irinotecan every 2 months, as compared with 6 months of FOLFIRINOX in patients with metastatic pancreatic cancer. [J Clin Oncol 2021;doi:10.1200/JCO.20.03329]

Among 276 patients (mean age, 63 years) enrolled between January 2015 and November 2016, the primary endpoint of PFS rate at 6 months was 42.9 percent in the leucovorin plus fluorouracil maintenance group, 34.1 percent in the sequential treatment group, and 47.1 percent in the group of patients who received 6 months of FOLFIRINOX.

Median OS was 11.2 months in the maintenance group, 7.3 months in the sequential treatment group, and 10.1 months in patients treated FOLFIRINOX for 6 months.

Median survival without deterioration in quality of life (QoL) scores was longer in the maintenance group (11.4 months) than in the sequential treatment group (7.5 months) or the group of patients who received 6 months of FOLFIRINOX (7.2 months).

Grade 3 or 4 neurotoxicity occurred more frequently in the maintenance group than in patients treated with FOLFIRINOX for 6 months (19.8 percent vs 10.2 percent), probably due to the higher cumulative dose of oxaliplatin in the former. The median ratio of received dose/targeted dose of oxaliplatin was 92 percent in the maintenance group, compared with 83 percent in patients who received 6 months of FOLFIRINOX.

According to the researchers, maintenance treatment with leucovorin plus fluorouracil appears to be feasible and effective in patients with metastatic pancreatic cancer controlled after 4 months of induction FOLFIRINOX chemotherapy.

“This study supports incorporation of a chemotherapy deintensification strategy for patients with metastatic pancreatic cancer, in whom preserving QoL and minimizing cumulative treatment-related toxicity are of paramount importance,” the researchers suggested.

“As survival rates for patients with pancreatic cancer continue to improve, building in maintenance approaches during their course of treatment warrants increased attention,” they added.