A sequential treatment strategy proved less effective than a maintenance strategy for patients with metastatic pancreatic cancer (mPC) in a phase 2 trial published in the Journal of Clinical Oncology.1
First-line treatment with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) has been shown to improve survival over gemcitabine in patients with metastatic pancreatic cancer, but FOLFIRINOX also increases neurotoxicity.2
The phase 2 PANOPTIMOX-PRODIGE 35 trial was designed to determine if a sequential treatment strategy or a maintenance strategy would decrease toxicity.
The trial’s intent-to-treat population included 273 patients with mPC. Their mean age at baseline was 63 years (range, 40-76 years).
Patients were randomly assigned to receive:
- 12 cycles of FOLFIRINOX (n=91)
- 4 months of FOLFIRINOX followed by leucovorin plus fluorouracil maintenance treatment for controlled patients (n=92)
- A sequential treatment regimen alternating gemcitabine and fluorouracil, leucovorin, and irinotecan (FIRGEM) every 2 months (n=90).
Progression-free survival (PFS) and overall survival (OS) outcomes were comparable between the FOLFIRINOX-alone arm and the FOLFIRINOX-maintenance arm but inferior in the FIRGEM arm. The FIRGEM regimen failed to achieve the goal of having 35 patients still alive and without progression at 6 months.
The 6-month PFS rate was 47.1% for FOLFIRINOX alone, 42.9% for FOLFIRINOX plus maintenance, and 34.1% for FIRGEM. The median PFS was 6.3 months, 5.7 months, and 4.5 months, respectively.
The median OS was 10.1 months for FOLFIRINOX alone, 11.2 months for FOLFIRINOX plus maintenance, and 7.3 months for FIRGEM.
Patients who received FOLFIRINOX plus maintenance had a longer median time to deterioration in their quality of life (11.4 months) when compared with patients in the FOLFIRINOX-alone arm (7.2 months) or the FIRGEM arm (7.5 months).
Based on these results, the study authors do not support the use of the sequential FIRGEM strategy, even though no neurotoxicity was observed with this regimen.
Grade 3-4 neurotoxicity occurred in 19.8% of patients who received FOLFIRINOX plus maintenance and 10.2% of patients who received FOLFIRINOX alone.
The authors reported that patients in the FOLFIRINOX-maintenance arm had a higher median dose intensity of oxaliplatin (92%) than those in FOLFIRINOX-alone arm (83%), which may explain the higher rates of grade 3-4 neuropathy observed in the maintenance arm.
“This study supports the incorporation of a chemotherapy deintensification strategy for patients with mPC, in whom preserving quality of life and minimizing cumulative treatment-related toxicity are of paramount importance,” the authors wrote. “As survival rates continue to improve for patients with pancreatic cancer, building in maintenance approaches during their treatment course warrants greater attention.”
Disclosures: This research was supported by Fédération Francophone de Cancérologie Digestive. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
- Dahan L, Williet N, Le Malicot K, et al. Randomized phase II trial evaluating two sequential treatments in first line of metastatic pancreatic cancer: Results of the PANOPTIMOX-PRODIGE 35 trial. J Clin Oncol. Published online July 21, 2021. doi:10.1200/JCO.20.03329
- Conroy T, Desseigne F, Ychou M, et al: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825. doi:10.1056/NEJMoa1011923