Cost‐effectiveness of immune checkpoint inhibitors for microsatellite instability–high/mismatch repair–deficient metastatic colorectal cancer

• Published in: Cancer 2019-01, Vol.125 (2), p.278-289
• Main Authors: Chu, Jacqueline N., Choi, Jin, Ostvar, Sassan, Torchia, James A., Reynolds, Kerry Lynn, Tramontano, Angela, Gainor, Justin F., Chung, Daniel C., Clark, Jeffrey W., Hur, Chin
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antineoplastic Agents, Immunological - economics; Antineoplastic Agents, Immunological - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - economics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer; Cancer therapies; Chemotherapy; Clinical trials; Colorectal cancer; Colorectal carcinoma; colorectal neoplasms; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - economics; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Computer simulation; Cost analysis; Cost-Benefit Analysis; Decision analysis; DNA Mismatch Repair; Drug Costs; Economic analysis; Economic impact; Economic models; Female; Fluorouracil - economics; Fluorouracil - therapeutic use; Humans; Immune checkpoint; Immunotherapy; Impact analysis; Inhibitors; ipilimumab; Ipilimumab - administration & dosage; Ipilimumab - economics; Leucovorin - economics; Leucovorin - therapeutic use; Leukemia; Male; Mathematical models; Medical research; Medical treatment; Metastases; Metastasis; Microsatellite Instability; Middle Aged; Mismatch repair; Monoclonal antibodies; nivolumab; Nivolumab - administration & dosage; Nivolumab - economics; Oncology; Organoplatinum Compounds - economics; Organoplatinum Compounds - therapeutic use; Patients; Quality-Adjusted Life Years; Repair; Stability; Survival; Targeted cancer therapy; Toxic diseases; Toxicity
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.31795

Background Patients with microsatellite instability–high (MSI‐H)/mismatch repair–deficient (dMMR) metastatic colorectal cancer (mCRC) show a significant response to checkpoint inhibitor therapies, but the economic impact of these therapies is unknown. A decision analytic model was used to explore the effectiveness and cost burden of MSI‐H/dMMR mCRC treatment. Methods The treatment of hypothetical patients with MSI‐H/dMMR mCRC was simulated in 2 treatment scenarios: a third‐line treatment and an exploratory first‐line treatment. The treatments compared were nivolumab, ipilimumab and nivolumab, trifluridine and tipiracil (third‐line treatment), and mFOLFOX6 and cetuximab (first‐line treatment). Disease progression, drug toxicity, and survival rates were based on the CheckMate 142, study of TAS‐102 in patients with metastatic colorectal cancer refractory to standard chemotherapies (RECOURSE), and Cancer and Leukemia Group B/Southwest Oncology Group 80405 trials. The analyzed outcomes included survival (life‐years), quality‐adjusted life‐years (QALYs), and incremental cost‐effectiveness ratios (ICERs). Results Ipilimumab with nivolumab was the most effective strategy (10.69 life‐years and 9.25 QALYs for the third line; 10.69 life‐years and 9.44 QALYs for the first line) in comparison with nivolumab (8.21 life‐years and 6.76 QALYs for the third line; 8.21 life‐years and 7.00 QALYs for the first line), trifluridine and tipiracil (0.74 life‐years and 0.07 QALYs), and mFOLFOX6 and cetuximab (2.72 life‐years and 1.63 QALYs). However, neither checkpoint inhibitor therapy was cost‐effective in comparison with trifluridine and tipiracil (nivolumab ICER, $153,000; ipilimumab and nivolumab ICER, $162,700) or mFOLFOX6 and cetuximab (nivolumab ICER, $150,700; ipilimumab and nivolumab ICER, $158,700). Conclusions This modeling analysis found that both single and dual checkpoint blockade could be significantly more effective for MSI‐H/dMMR mCRC than chemotherapy, but they were not cost‐effective, largely because of drug costs. Decreases in drug pricing and/or the duration of maintenance nivolumab could make ipilimumab and nivolumab cost‐effective. Prospective clinical trials should be performed to explore the optimal duration of maintenance nivolumab. Patients with microsatellite instability–high/mismatch repair–deficient metastatic colorectal cancer show a significant response to checkpoint inhibitor therapies, but the economic impact of these therapies is unknown. This mo