Modified FOLFIRINOX as a second-line therapy following gemcitabine plus nab-paclitaxel therapy in metastatic pancreatic cancer

Abstract

Purpose There is no established second-line treatment after failure of gemcitabine plus nab-paclitaxel (GnP) therapy for metastatic pancreatic cancer (MPC). This study aimed to evaluate the efficacy and tolerability of the modified FOLFIRINOX (mFFX) as a second-line therapy for MPC and investigate prognostic factors for survival.Methods From 2015–2019, we retrospectively reviewed the medical records of patients receiving mFFX for MPC after failure of GnP therapy. Patients were treated every 2 weeks with mFFX (intravenous oxaliplatin 85 mg/m2, intravenous irinotecan 150 mg/m2, and continuous infusion of 5-fluorouracil 2,400 mg/m2 for 46 hours without bolus infusion) until disease progression, patient refusal, or unacceptable toxicity.Results In total, 104 patients received mFFX. The median overall survival (OS) was 7.0 months (95% confidence interval [CI]: 6.2-9.8) and the progression-free survival (PFS) 3.9 months (95% CI 2.8-5.0). The objective response rate was 10.6% and the disease control rate 56.7%. The median relative dose intensities of oxaliplatin, irinotecan, and infusional 5-FU were 80.0% (range 21.5-100%), 77.2% (range 38.1-100%), and 85.9% (range 36.9-100%), respectively. Grade 3-4 toxicities were reported in 57 patients (54.8%), including neutropenia, leukopenia, anemia, febrile neutropenia, and peripheral sensory neuropathy. Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify the patients into good (n = 38), intermediate (n = 47), and poor (n = 19) prognostic groups. The median OS and PFS time was 14.7 (95% CI 7.6-16.3) and 7.6 months (95% CI 4.1-10.5) for the good prognostic factors, 6.5 (95% CI 5.5-10.0) and 3.6 months (95% CI 2.7-4.8) for the intermediate prognostic factors and 5.0 (95% CI 2.9-6.6) and 1.7 months (95% CI 0.9-4.3) for the poor prognostic factors, respectively.Conclusions The mFFX showed to be a tolerable second-line treatment for MPC after GnP failure. Our prognostic model might be useful for deciding whether mFFX is indicated in this setting.

Modified FOLFIRINOX versus sequential chemotherapy (FOLFIRI/FOLFOX) as a second‐line treatment regimen for unresectable pancreatic cancer: A real‐world analysis

“…In the phase III ACCORD11 trial, the efficacy of FOLFIRINOX as a first‐line treatment was superior to that of GEM, 5 although the trial revealed several safety concerns, such as febrile neutropenia and anorexia. The efficacy and safety of mFOLFIRINOX as a first‐line treatment have been demonstrated 6,24 and those of mFOLFIRINOX as a second‐line treatment have been reported; the reported median OS with mFOLFIRINOX as a second‐line treatment ranges from 7.0 to 10.3 months 18–20 . In our study, the median OS of 10.6 months in the mFOLFIRINOX group was not inferior to that reported in previous studies, although this is a comparison between different trials and requires careful consideration.…”

“…Although the regulatory approval of nal‐IRI/5‐FU/LV has clarified the principle of treatment, the selection of second‐line chemotherapy regimen for unresectable pancreatic cancer is controversial. In such circumstances, several studies have confirmed the efficacy and safety of mFOLFIRINOX as a second‐line treatment; its clinical usefulness as a first‐line treatment has already been established 6,18,19,24 . The consideration of mFOLFIRINOX, the standard first‐line treatment alongside GnP, as a second‐line treatment is natural and reasonable in cases where it has not been used as a first‐line treatment.…”

“…Several studies have reported the clinical utility of mFOLFIRINOX as a second‐line treatment for patients with unresectable pancreatic cancer 18–20 . mFOLFIRINOX has a better safety profile than FOLFIRINOX as first‐line therapy 6 .…”

Advanced Pancreatic Ductal Adenocarcinoma: Moving Forward

“…Other second-line therapy options after GA, are FOLFIRINOX/mFOLFIRINOX and FOLFIRI, especially where Nal-IRI is not available. A recently published retrospective study showed, for patients in good performance status (ECOG 0/1) with progressing disease on GA, showed a median OS of 7.0 months under a second-line treatment with mFOLFIRINOX (omission of 5-FU bolus) [ 31 ]. The median OS after the start of first-line therapy was 15.9 months.…”

Real‐world prognostic factors for survival among treated patients with metastatic pancreatic ductal adenocarcinoma

“…Real-world studies reported in the literature have included estimates of the prognostic impact of patient and disease characteristics in patients receiving systemic therapy for mPDAC. [17][18][19][20][21] Such studies have been limited in sample size due to a reliance on one or a limited number of study centers or a focus on patients receiving a particular drug regimen. This has limited their usefulness for guiding decision-making in the treatment of patients with mPDAC.…”