Efficacy and Safety of Different Sequences for mFOLFIRINOX (or SOXIRI) and Gemcitabine Plus Albumin-Bound Paclitaxel in Unresectable Pancreatic Cancer

Silan Huang,1,* Lingli Huang,1,* Dongsheng Zhang,2 Qi Jiang,1 Fenghua Wang,2 Guifang Guo1 1VIP Department, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 2Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guifang Guo, VIP Department, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China, Email [email protected] Fenghua Wang, Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China, Email [email protected]: This study aimed to evaluate and compare the therapeutic efficacy and adverse effects of two sequential treatment strategies in patients with unresectable advanced pancreatic cancer (aPC), albumin-bound-paclitaxel plus gemcitabine administered follow by mFOLFIRINOX or SOXIRI (AG-F(S)FXm) versus the reverse sequence regimen F(S)FXm-AG.Methods: In this retrospective analysis, patients with unresectable advanced pancreatic cancer (aPC) who received either AG-F(S)FXm or F(S)FXm-AG were included. Key endpoints were overall survival (OS), progression-free survival (PFS), and treatment-related toxicity. Survival outcomes were assessed using Kaplan-Meier curves, and differences between groups were examined through hazard ratios (HR) and corresponding p-values.Results: A total of 107 patients were analyzed, including 49 who underwent AG-F(S)FXm and 58 who received F(S)FXm-AG. The median OS was 14.60 months for F(S)FXm-AG and 12.20 months for AG-F(S)FXm (HR: 1.04, 95% CI: 0.69– 1.57, p= 0.86). Median PFS1, median PFS2 and median total PFS (tPFS) were 5.20 months versus 4.83 months (HR: 0.81, 95% CI: 0.54– 1.21, p= 0.3), 4.53 months versus 5.77 months (HR: 1.15, 95% CI: 0.71– 1.88, p= 0.60) and 13.80 months versus 12.80 months (HR: 0.90, 95% CI: 0.55– 1.48, p= 0.67) for F(S)FXm-AG versus AG-F(S)FXm. Given their comparable efficacy, we further compared the safety profiles of both regimens. The toxicity profiles differed between the two sequential treatments. Leukopenia was more common with first-line AG, while gastrointestinal toxicity, fatigue, and sensory neuropathy were more frequent with first-line F(S)FXm. Additionally, elevated aspartate aminotransferase was more often reported with second-line AG.Conclusion: Both AG-F(S)FXm and F(S)FXm-AG demonstrated comparable efficacy in treating aPC, with F(S)FXm-AG showing a trend toward improved outcomes. The choice of sequential treatment should be guided by toxicity profiles and patient-specific factors. Further prospective studies are warranted to optimize treatment sequencing and personalize therapy for improved patient outcomes.Keywords: advanced pancreatic cancer, AG, mFOLFIRINOX, SOXIRI and efficacy