Abstract
The BEACON trial showed that combination therapy with encorafenib (BRAF inhibitor) and cetuximab (EGFR inhibitor) was associated with prolonged overall survival compared with standard chemotherapy in patients with metastatic BRAF variant colorectal cancer. However, the cost-effectiveness of using these agents in this clinical setting is unknown. To create a cost-effectiveness model to compare doublet therapy (encorafenib plus cetuximab) with standard chemotherapy (cetuximab plus irinotecan or cetuximab plus folinic acid, fluorouracil, and irinotecan) in treating patients with metastatic BRAF variant colorectal cancer. This economic evaluation constructed a Markov model to compare the lifetime cost and utility of doublet therapy and standard chemotherapy. Parametric survival modeling was used to extrapolate the effectiveness of each line of therapy from large clinical trials. One-way and probabilistic sensitivity analyses assessed the uncertainty in the model. Patients mirrored the cohorts in the BEACON trial: they had metastatic BRAF variant colorectal cancer and were followed up as they progressed through multiple lines of therapy, best supportive care, and death. Data collection and data analysis were performed from November 15, 2019, to July 14, 2020. The main outcome was the incremental cost-effectiveness ratio, which was calculated using the cumulative cost and effectiveness in quality-adjusted life years (QALYs), of doublet therapy compared with standard chemotherapy. The model patient cohort had a mean age of 61 years, and 53% of the patients were women, 66% had 1 previous line of therapy, and 8% had high microsatellite instability. Doublet therapy was associated with an improvement of 0.15 QALYs compared with standard chemotherapy. However, the incremental cost of doublet therapy was $78 233, leading to an incremental cost-effectiveness ratio of $523 374 per QALY gained. Concomitant decreases in the price of encorafenib and cetuximab are needed to achieve cost-effectiveness at a willingness-to-pay threshold of $150 000 per QALY gained. This study found that doublet therapy for metastatic BRAF variant colorectal cancer was unlikely to be cost-effective under current pricing. Cost-effectiveness needs to be considered in clinical trial design, particularly when combining new therapies with non-cost-effective treatments that are coadministered without a fixed duration.
Highlights
Colorectal cancer is the third most common cancer and is a leading cause of cancer death in the United States.[1]
This study found that doublet therapy for metastatic BRAF variant colorectal cancer was unlikely to be cost-effective under current pricing
The incremental costeffectiveness ratio (ICER) for doublet therapy was $523 374 per quality-adjusted life year (QALY) gained compared with the strategy of using standard chemotherapy with cetuximab plus irinotecan or cetuximab plus FOLFIRI
Summary
Colorectal cancer is the third most common cancer and is a leading cause of cancer death in the United States.[1]. In clinical studies that have combined BRAF inhibitors with monoclonal antibodies against EGFR or mitogen-activated protein kinase kinase (MEK), BRAF inhibitors with monoclonal antibodies were shown to have improved response compared with BRAF inhibition alone.[8,9] More recently, in a large phase 3 study (BEACON CRC [A Multicenter, Randomized, Open-Label, 3-Arm Phase 3 Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer]), patients with BRAF variant colorectal cancer were randomized to triplet therapy with encorafenib (BRAF inhibitor), binimetinib (MEK inhibitor), and cetuximab (EGFR inhibitor); doublet therapy with encorafenib and cetuximab; or standard chemotherapy with cetuximab plus irinotecan hydrochloride or cetuximab plus folinic acid, fluorouracil, and irinotecan (FOLFIRI).[2] The BEACON study demonstrated improved outcomes with triplet and doublet therapy, with a median overall survival of 9.3 months for both regimens vs 5.9 months for standard chemotherapy.[10] Based on these results, doublet therapy was approved by the US Food and Drug Administration for use in BRAF variant colorectal cancer
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