OBJECTIVES: To review and compare clinically meaningful differences in terms of clinical benefits (Ellis et al. J Clin Oncol 2014; 32(12): 1277-80.) and incremental costs of adding a single agent to an existing regimen (including the addition of bevacizumab to trifluridine/tipiracil [FTD/TPI+BEV]) for advanced gastrointestinal cancers (aGIC) in the United States (US).

METHODS: Benchmarking of incremental benefits/costs was based on published Phase III trial data for qualifying regimens that included ≥1 branded agent, were approved for the treatment of aGIC in the US, and comprised combination therapies for which a single agent was added to an existing regimen. Clinical benefits were summarized based on overall survival (OS) and progression-free survival (PFS); costs (2024US$) included drugs and administration. Drug costs were based on projected utilization (median treatment duration) and price/unit; administration costs were based on published fee schedules. Adverse events (AEs) and treatment discontinuation were also summarized.

RESULTS: Eight regimens—FTD/TPI+BEV, paclitaxel+ramucirumab, fluorouracil+irinotecan+leucovorin (FOLFIRI)+ziv-aflibercept, FOLFIRI+ramucirumab, durvalumab+tremelimumab, durvalumab+ gemcitabine+cisplatin, and nivolumab+chemotherapy (two)—qualified for inclusion after targeted literature review. Addition of BEV to FTD/TPI yielded greatest improvements in clinical benefits versus single agents added to comparator regimens: increase in OS (median), 3.3 vs. 1.3 – 2.6 months; increase in PFS (median), 3.2 vs. -0.2 – 2.2 months. Differences in AEs and treatment discontinuation were generally favorable/comparable for FTD/TPI + BEV. Incremental cost of adding BEV to FTD/TPI was lower than addition of single agents to other regimens: absolute increment, $26,441 vs. $64,730 – $332,705; percentage increment, 32% vs. 150% – 6,080%.

CONCLUSIONS: Combination of BEV and FTD/TPI (vs. FTD/TPI) for the treatment of metastatic colorectal cancer yielded greater clinically meaningful benefits related to OS/PFS, and incremental costs of adding BEV to FTD/TPI were lower than addition of single agents to other regimens for aGIC that are currently used in US clinical practice.