High Cost, Minimal Benefit for Bevacizumab in Metastatic CRC

Bevacizumab as first-line therapy for metastatic CRC equated to an incremental cost-effectiveness ratio of more than half a million dollars per QALY.

Use of bevacizumab as a first-line therapy for metastatic colorectal cancer equated to an incremental cost-effectiveness ratio (ICER) of more than half a million dollars per quality-adjusted life year (QALY), according to the results of a US cost-effectiveness analysis published in the Journal of Clinical Oncology. Use of the VEGF inhibitor beyond progression had a cost-effectiveness ratio of more than $350,000 per QALY, the study showed.

“The threshold of $50,000 to $100,000 per QALY is frequently justified as a definition for a cost-effective healthcare intervention based on the cost effectiveness of dialysis,” wrote researchers led by Daniel A. Goldstein, MD, of Winship Cancer Institute of Emory University, Atlanta. “The probabilistic sensitivity analyses revealed that 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.”

Goldstein and colleagues developed two models to compare the cost and effectiveness of fluorouracil, leucovorin and oxaliplatin with or without bevacizumab in first-line treatment of metastatic colorectal cancer, and subsequent fluorouracil, leucovorin, and irinotecan with or without bevacizumab in second-line treatment. The primary outputs of the models included total cost, life years (LYs), QALYs, and ICERs. Survival benefit assumptions were taken from the N01966 trial that showed a 1.4-month median overall survival benefit when bevacizumab was added to FOLFOX and XELOX.

Results of the analysis showed that the use of bevacizumab as first-line treatment provided an additional 0.10 QALYs at a cost of $59,361. This translated to an incremental cost-effectiveness ratio of $571,240 per QALY. When continued into second-line patients gained 0.11 QALYs at a cost of $39,209, which translated to an incremental cost-effectiveness ratio of $364,083 per QALY.

Goldstein and colleagues pointed out several limitations to their research including the fact that the models were based on data from a previously published study, that they used reimbursement rates from Medicare, which are generally lower than those of private insurers, and that the model was static and did not account for differences in drug acquisition costs over time.

In an editorial that accompanied this article, Leonard B. Saltz, MD, of the Memorial Sloan Kettering Cancer Center, discussed some of the overall flaws of the current healthcare system of the United States, including the fact that the FDA does not consider price in its approval process and that Medicare has no ability to negotiate prices of drugs or consider cost effectiveness information.

Looking at the data from Goldstein et al, he commented: “As noted, the potential limitations in methodology and in the published clinical data may give some cause for concern that these numbers may need to be considered as approximations. However, even if given a wide margin for error, the lower limit of whatever CIs we might reasonably choose to use is still going to represent a substantial expenditure for what all available data would indicate is a relatively modest incremental survival improvement.”

Saltz wrote that, in fact, cost-effectiveness research has become “an academic exercise of no meaningful consequence,” with the healthcare community agreeing that the cost of many new drugs are an issue, but doing little about it.

“Until we somehow manage to find the collective will to confront the data and acknowledge the limitations of some of our therapeutic advances and assign a realistic value to them accordingly, and to either demand a lower price for the intervention or not use it, we are consigned to a future that will ultimately show us just what unsustainable really means,” Saltz wrote.