Study: Spending Increasing for Cancer Therapies Without Evidence of Overall Survival

Spending on oral therapies that treat patients with cancer without a documented overall survival benefit has increased and even surpassed spending on therapies with such clinical data, according to a recent study published in JAMA Internal Medicine.

Investigators assessed 44 new oral targeted drugs dispensed between 2011 and 2018. Most patients (97%) received drugs for which evidence of overall survival from randomized clinical trials existed. But investigators found that a growing share of patients received drugs without such data: from 12.7% in 2011 to 58.8% in 2018. Cumulative spending on drugs without overall survival data was $1.8 billion and surpassed that of drugs with documented overall survival benefit of $1.7 billion by the end of 2018.

Anita Wagner, Pharm.D., Dr.PH.

“The results we describe in our study — increasing use of and spending on cancer drugs without documented overall survival benefit — reflect characteristics of the U.S. cancer drug ecosystem, which includes drug development, regulation, pricing, advertising, and reimbursement,” lead author Anita Wagner, Pharm.D., Dr.PH., associate professor of population medicine at Harvard Medical School and Harvard Pilgrim Health Care Institute, said in an email to Formulary Watch. She is also director of the ethics program at Point32Health, the parent company of Harvard Pilgrim Health Care and Tufts Health Plan.

Of the 44 drugs investigators analyzed, 34 (77.3%) were supported by at least one randomized clinical trial for at least one indication; 10 drugs (22.7%) were approved on the basis of single-arm studies or noncomparative trials alone. Only 11 drugs (25%) had documented, statistically significant overall survival benefit for at least one indication in FDA-approved labels by the end of 2018, and four those had overall survival as primary end point.

The investigators suggested that the increased spending on cancer drugs without overall survival data is a result of several factors, including: increasingly lenient FDA approvals, drugs advertised directly to consumers, no price regulation, fragmented purchasing and reimbursement systems, coverage mandates, and limited ability by payers to negotiate prices.

Given the U.S cancer drug ecosystem, payers have limited options to address the challenges posed by expensive drugs with uncertain benefits, Wagner said. “Nevertheless, as key actors in a complex system, payers can play a role in member and clinician education about evidence of benefits and risks. They can target drug coverage according to evidence, seek risk sharing contracts with pharmaceutical companies, and they can publicly advocate for better evidence.”

The authors suggested in the paper that value-based pricing might reduce the cost of some drugs with high spending amounts. They point to Nerlynx (neratinib), which was ranked 11th in this study in terms of spending. Developed by Puma Biotech, this therapy was approved in 2017 as adjuvant treatment of adult patients with early stage HER2-positive breast cancer. One study suggested Nerlynx’s price would need to be reduced by 85% for it to be cost-effective at a willingness-to-pay threshold of $150,000 per quality-adjusted life-year gained.

Wagner said policy changes in this complex ecosystem likely need to be multi-pronged. “They are likely challenging and controversial as most require cooperation of stakeholders with different priorities,” she said. “They include, for example, validated surrogate end points with pre-defined thresholds predictive of clinically meaningful benefit.”

But she indicated that some changes may be more readily feasible than others. Among those may be FDA efforts to make explicit and easily accessible for patients, their clinicians, and others what is known and what is not known about the clinical benefits of newly approved highly priced cancer drugs.

“Such efforts could start with consistent documentation of overall survival information in FDA-approved labeling as we have suggested based on another recent study and clear visual alerts in labels of limited evidence underlying accelerated approvals akin to black box warnings as colleagues at Institute for Clinical and Economic Review have suggested.”