Bevacizumab costly with limited incremental benefit in CRC study

Reuters Health Information: Bevacizumab costly with limited incremental benefit in CRC study

Bevacizumab costly with limited incremental benefit in CRC study

Last Updated: 2015-02-19

By Megan Brooks

NEW YORK (Reuters Health) - A new study questions the cost-effectiveness of bevacizumab in both the first- and second-line settings of metastatic colorectal cancer (mCRC) treatment.

"Our study demonstrates the high cost of the drug, with limited incremental benefit," Dr. Daniel Goldstein, of the Winship Cancer Institute of Emory University in Atlanta, told Reuters Health by email.

Adding bevacizumab to fluorouracil-based chemotherapy is a standard of care for previously untreated mCRC. It's also acceptable to continue bevacizumab following disease progression based on a greater than one month increase in median overall survival seen in a randomized trial. Yet no U.S.-based cost-effectiveness study on use of bevacizumab in mCRC had been done, until now.

Dr. Goldstein and colleagues developed two cost-effectiveness models comparing fluorouracil, leucovorin, and oxaliplatin with or without bevacizumab in the first-line treatment of mCRC, and fluorouracil, leucovorin, and irinotecan with or without bevacizumab in the second-line treatment of the disease.

In both scenarios, bevacizumab provided only modest incremental benefit at high incremental cost per quality-adjusted life-year (QALY), they found.

In both the first- and second-line models, adding bevacizumab prolonged the median overall survival by just six weeks and increased costs by $60,000 and $40,000, respectively, they report. Bevacizumab proved more cost-effective in the second-line setting because it's used for a shorter period of time, they say.

Still, the researchers say in the "best-case scenario" the incremental cost-effectiveness ratio (ICER) remained higher than $200,000 per QALY. In a probabilistic sensitivity analysis, the probability of bevacizumab being cost-effective was 0% in the first- and second-line settings for a willingness-to-pay threshold of $100,000 per QALY, they report. This suggests a "high likelihood that bevacizumab exceeds the usually accepted values for cost-effective incremental costs of care."

Other studies outside the U.S. have analyzed the cost-effectiveness of bevacizumab in mCRC. A British study found that adding bevacizumab to FOLFIRI in first-line treatment cost 62,857 pounds (US$102,000) per QALY. A Canadian study found that adding bevacizumab yielded an ICER of Canadian $131,600 (US$120,000) per QALY, whereas in Japan, it was 13.5 million yen (US$113,000) per QALY.

Dr. Goldstein told Reuters Health, "If an effective biomarker were available to select the patients most likely to benefit, the drug would have greater value. This study demonstrates the need for oncology drugs entering the U.S. marketplace to have a cost relative to their benefit."

The researchers note that they used reimbursement rates provided by Medicare, which are generally lower than reimbursement rates for private insurers. Also, the model was static and assumed no differences in drug acquisition costs over time, which may have led to an overestimation of the cost of bevacizumab when it goes off patent.

They conclude, "In the era of personalized medicine, the needs of patients with mCRC or other malignancies warrant the development of new therapeutic technologies, but with the dramatic rises in drug prices over the last decades, the use of new treatments should be tailored to the patients who are most likely to benefit."

"In the current environment, costly drugs face few barriers to coverage and adoption by physicians," they continue. "However, the process for new drug approval and the incorporation of drugs into treatment formularies and guidelines may eventually force physicians and policymakers to confront tradeoffs between cost and benefit more explicitly. Data from this study and others like it provide a starting point for such discussions."

The study was published online February 17 in Journal of Clinical Oncology.

Also in this issue of JCO are results of the LEA trial, the first phase 3 study investigating the value of adding bevacizumab (15 mg/kg every three weeks) to endocrine therapy (letrozole or fulvestrant) in the first-line treatment of hormone receptor-positive/HER2-negative locally recurrent or metastatic breast cancer.

On the basis of prior studies, the LEA study protocol assumed a median progression-free survival (PFS) for the control arm (endocrine therapy only) of nine months, and required a median PFS of at least 13 months for the bevacizumab arm to show efficacy, defined as a hazard ratio of 0.692 corresponding to the four-month increase in median PFS.

In this study involving 380 women, adding bevacizumab to endocrine therapy failed to provide a statistically significant increase in PFS or overall survival, and therefore "should not be recommended," report Dr. Miguel Martin of the Universidad Complutense in Madrid and colleagues.

"Forthcoming results from a similar trial with 400 patients run by the Cancer and Leukemia Group B (ClinicalTrials. gov identifier: NCT00601900) will provide additional insights into the value of ET-B in patients with hormone receptor-positive metastatic breast cancer," they point out.

The cost-effectiveness study had no commercial funding. The LEA trial was supported by F. Hoffman-LaRoche, which also provided bevacizumab. Complete disclosure information for study authors is available at


J Clin Oncol 2015.

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