Moving the Target on the Optimal Adjuvant Strategy for Resected Pancreatic Cancers: A Systematic Review with Meta-Analysis

Abstract

Combination regimens have shown superiority over single agents in the adjuvant treatment of resected pancreatic cancer (PC), but there are no data supporting definition of the best regimen. This work aimed to compare the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel in PC patients. A meta-analysis was performed for direct comparison between trials comparing combination regimens and gemcitabine monotherapy. Subsequently, an indirect comparison was made between trials investigating the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel because of the same control arm (gemcitabine). A total of three studies met the selection criteria and were included in our indirect comparison. Indirect comparisons for efficacy outcomes showed a benefit in terms of DFS (disease-free survival)/EFS (event-free survival)/RFS (relapse-free survival) for both mFOLFIRINOX versus gemcitabine+capecitabine (HR 0.69, 95% CI 0.52–0.91) and versus gemcitabine+nab/paclitaxel (HR 0.67, 95% CI 0.50–0.90). No significant advantage was registered for OS (overall survival). Indirect comparisons for safety showed an increase in terms of G3-5 AEs (with the exception of neutropenia) for mFOLFIRINOX versus gemcitabine+capecitabine (RR 1.24, 95% CI 1.03–1.50), while no significant differences were observed versus gemcitabine+nab/paclitaxel. According to our results, mFOLFIRINOX is feasible and manageable and could represent a first option for fit PC resected patients.

Prognostic Value of Drug Targets Predicted Using Deep Bioinformatic Analysis of m6A-Associated lncRNA-Based Pancreatic Cancer Model Characteristics and Its Tumour Microenvironment

“…The main treatment modality is surgery supplemented with chemotherapy and immune-targeted therapy; however, the resectability rate using surgery is only 15–20%, and adjuvant treatments show limited effects. Although, Studies have shown that nab-paclitaxel and mFOLFIRINOX (Oxaliplatin + Irinotecan+5-Fluorouracil + Calcium folinate) can effectively improve the survival rate of pancreatic cancer patients ( De Luca et al, 2018 ; Galvano et al, 2020 ). However, the overall 5-years survival rate of less than 8% ( Shaib et al, 2016 ; Ying et al, 2016 ; Mcguigan et al, 2018 ).…”

Comparative Safety and Efficacy of Therapeutic Options in Resectable and Advanced/Metastatic Pancreatic Cancer: A Systematic Review and Indirect Comparison

“…The deviations could be attributed to not including febrile neutropenia and sensory neuropathy in the study because of the lack of data in some of the trials. Through systematic reviews and meta-analyses performed by Galvano et al [4], Oneda and Zaniboni [26], and Kamarajah et al [7], FOLFIRINOX was found to be a superior adjuvant treatment option as compared to gem-nab/P or gem-cap for survival outcomes in resectable pancreatic cancer. The AE findings for resectable pancreatic cancer for this study were similar to that of Galvano et al [4] wherein grade 3/4 AE risk of FOLFIRINOX was higher compared to gem-cap and slightly lower compared to gem-nab/P [4].…”

“…There are no direct head-tohead trials comparing these chemotherapy treatments. Therefore, an indirect comparison was needed to assess superiority (i.e., efficacy and safety) of FOLFIRINOX compared to gemcitabine-based chemotherapy for both resectable and advanced pancreatic cancer [4][5][6][7][8][9].…”

Cost-effectiveness analysis of FOLFIRINOX vs gemcitabine with nab-paclitaxel as adjuvant treatment for resected pancreatic cancer in the United States based on PRODIGE-24 and APACT trials

“…[6][7][8] FOLFIRINOX (combination of 5 fluorouracil, leucov¬orin, oxaliplatin, and irinotecan) or gemcitabine with nabpaclitaxel (GemNab) are the recommended adjuvant chemotherapy regimens for pancreatic cancer. 9,10 In the phase 3 PRODIGE-24 study, patients diagnosed with pancreatic cancer who underwent R0 or R1 resection were randomized to either FOLFIRINOX or gemcitabine monotherapy and evaluated for disease-free survival (DFS), overall survival (OS), and toxicity. Results indicated significantly longer OS and DFS in patients treated with FOLFIRINOX vs gemcitabine (DFS: 21.6 months vs 12.8 months, hazard ratio [HR] = 0.58 [0.46-0.73]; OS: 54.4 months vs 35 months, HR = 0.64 [0.48-0.86]).…”