Journal Article

Meta-analysis examining overall survival in patients with pancreatic cancer treated with second-line 5-fluorouracil and oxaliplatin-based therapy after failing first-line gemcitabine-containing therapy: effect of performance status and comparison with other regimens

Ryoo, Baek-Yeol, Lee, Myung Ah, Muñoz, Andrés, Lonardi, Sara, Hecht, J. Randolph, Gracián, Antonio Cubillo, Lin, Yong, Bendell, Johanna, Wainberg, Zev A., Feeney, Kynan, Hung, Annie

2020

Overview

Background Pancreatic cancer has a poor prognosis and few choices of therapy. For patients with adequate performance status, FOLFIRINOX or gemcitabine plus nab-paclitaxel are preferred first-line treatment. 5-Fluorouracil (5-FU)–based therapy (e.g. FOLFIRI, OFF, or FOLFOX) are often used in patients who previously received gemcitabine-based regimens. A systematic review was conducted of the safety and efficacy of FOLFOX for metastatic pancreatic cancer following prior gemcitabine-based therapy. A Bayesian fixed-effect meta-analysis with adjustment of patient performance status (PS) was conducted to evaluate overall survival (OS) and compare outcomes with nanoliposomal irinotecan combination therapy. Methods PubMed.gov , FDA.gov , ClinicalTrials.gov , congress abstracts, Cochrane.org library, and EMBASE database searches were conducted to identify randomized controlled trials of advanced/metastatic disease, prior gemcitabine-based therapy, and second-line treatment with 5-FU and oxaliplatin. The database search dates were January 1, 1990–June 30, 2019. Endpoints were OS and severe treatment-related adverse events (TRAEs). Trial-level PS scores were standardized by converting Karnofsky grade scores to Eastern Cooperative Oncology Group (ECOG) Grade, and overall study-weighted PS was calculated based on weighted average of all patients. Results Of 282 studies identified, 11 randomized controlled trials ( N  = 454) were included in the meta-analysis. Baseline weighted PS scores predicted OS in 10 of the 11 studies, and calculated PS scores of 1.0 were associated with a median OS of 6.3 months (95% posterior interval, 5.4–7.4). After adjusting for baseline PS, FOLFOX had a similar treatment effect profile (median OS, range 2.6–6.7 months) as 5-FU/leucovorin plus nanoliposomal irinotecan therapy (median OS, 6.1 months; 95% confidence interval 4.8–8.9). Neutropenia and fatigue were the most commonly reported Grade 3–4 TRAEs associated with FOLFOX. Conclusions Baseline PS is a strong prognostic factor when interpreting the efficacy of 5-FU and oxaliplatin-based therapy of pancreatic cancer after progression on first-line gemcitabine-based regimens. When baseline PS is considered, FOLFOX has a similar treatment effect as 5-FU and nanoliposomal irinotecan therapy and a comparable safety profile. These findings suggest that 5-FU and oxaliplatin-based therapies remain an acceptable and alternative second-line treatment option for patients with pancreatic cancer and adequate PS (e.g. ECOG 0–1) following gemcitabine treatment.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 5-Fluorouracil / Analysis / Antineoplastic Combined Chemotherapy Protocols - pharmacology / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Bayesian analysis / Biomedical and Life Sciences / Biomedicine / Cancer metastasis / Cancer patients / Cancer Research / Cancer therapies / Care and treatment / Chemotherapy / Clinical trials / Complications and side effects / Deoxycytidine - analogs & derivatives / Deoxycytidine - pharmacology / Deoxycytidine - therapeutic use / Development and progression / Drug Resistance, Neoplasm / Drug-Related Side Effects and Adverse Reactions - diagnosis / Drug-Related Side Effects and Adverse Reactions - epidemiology / Drug-Related Side Effects and Adverse Reactions - etiology / Experimental therapeutics and drug development / Fluorouracil / Fluorouracil - pharmacology / Fluorouracil - therapeutic use / FOLFOX / Gemcitabine / Health Promotion and Disease Prevention / Humans / Irinotecan / Karnofsky Performance Status / Leucovorin - pharmacology / Leucovorin - therapeutic use / Medical prognosis / Medicine/Public Health / Meta-analysis / Metastases / Metastasis / Metastatic / Neutropenia / Oncology / Online searching / Operating systems (Software) / Organoplatinum Compounds - pharmacology / Organoplatinum Compounds - therapeutic use / Oxaliplatin / Oxaliplatin - pharmacology / Oxaliplatin - therapeutic use / Paclitaxel / Pancreatic cancer / Pancreatic Neoplasms - diagnosis / Pancreatic Neoplasms - drug therapy / Pancreatic Neoplasms - mortality / Patient outcomes / Patients / Performance status / Political activity / Political aspects / Prognosis / Randomized Controlled Trials as Topic / Research Article / Risk Factors / Studies / Surgical Oncology / Survival / Survival Analysis / Treatment Outcome / Tumors