Pivotal cancer clinical trial data may lack generalizability in older adults with Medicare, a study published online today in JAMA Network Open found.
Pivotal cancer clinical trial data may lack generalizability in older adults with Medicare, a study published online today in JAMA Network Open found.1 Results of the analysis suggest that newly approved drugs should be used with caution when treating older adults with cancer.
Clinical trials are an integral aspect of cancer drug development, giving researchers, regulatory bodies, and clinicians the safety and efficacy data necessary to make the best possible drugs available to patients. But it has long been known that disparities exist in cancer care overall and in clinical trial participation, including those related to racial, socioeconomic, and geographic factors.2
Investigators aimed to determine whether overall survival (OS), duration of treatment, and dose reduction trends in Medicare beneficiaries treated with FDA-approved oncology drugs for metastatic solid cancers aligned with the results seen in clinical trials. The retrospective cohort study encompassed data from 11,828 trial participants (56.8% male, 64.3% White) with a mean age of 61.8 years and 9178 Medicare beneficiaries in the Surveillance, Epidemiology, and End Results (SEER) database (52.3% male, 81.0% White) with a mean age of 72.7 years.
Cancer drug approvals for metastatic and locally advanced disease indications between 2008 and 2013 were assessed in the analysis, with 22 drugs for 29 indications included in the study. Data from patients whose disease matched the FDA indication and who received at least 1 dose of the intravenous or oral therapy were included in the analysis, and because the goal was to assess real-world use of the agents, the population was not further limited to those who would fit the clinical trial eligibility criteria.
Of the 29 total indications, 28 showed shorter OS in Medicare patients versus in the intervention arms of clinical trials, with the exception being afatinib in non–small cell lung cancer treatment. The median OS in Medicare beneficiaries was 59.9% of the OS in clinical trial patients receiving the same treatment for the same indication (median difference, -6.3 months; -28.7 to 2.7).
Medicare patients also had a shorter median duration of therapy than trial participants in 23 of the indications, with a median difference of 1.9 months (range, -12.4 to 1.4 months). Dose reductions or single prescriptions were also more common among Medicare patients in 8 of the 9 indications with dose reduction information in the package insert or trial publication.
The study authors present several factors that could potentially explain the differences between clinical trial outcomes and real-world results.
First, the mean age of Medicare patients in the analysis was 73 years versus 62 years in the clinical trial participants. Given the toxicity of cancer treatment and the prevalence of comorbidities with advanced age, this may contribute to earlier therapy discontinuation, interruptions in treatment, or suboptimal dosing, which can impact survival. Shorter durations of therapy in the Medicare population were likely due to factors in addition to age, “including comorbidities, performance status, tumor prognostic factors, access to care, racial disparities, systemic discrimination, and other socioeconomic factors that could lead to differential treatment and outcomes in the Medicare population compared with clinical trial participants,” the authors noted.
Only 6 of the drugs in the analysis included age-specific survival data in trial publications or FDA packaging, but those data showed similar survival in older and younger study participants, meaning age alone may not be an explanation for the findings in the analysis. Comorbidities or illness from more advanced or aggressive cancers may also factor in, given that patients with heavily pretreated or rapidly progressing disease are often excluded from trials, the authors suggest.
Overall, the findings indicate that pivotal trial data may not reflect real-world clinical practice outcomes in Medicare patients who undergo cancer treatment. This makes it more difficult for oncologists to assess the risks and benefits of a particular cancer treatment or determine optimal dosing strategies for patients in this population.
“These findings raise concerns regarding the generalizability of clinical trial data for treatment decision-making in Medicare patients,” the authors concluded. “Furthermore, prescribing patterns in Medicare patients require additional scrutiny to ensure optimal dosing to avoid overtreatment or undertreatment in this population. Pivotal trials can be improved, and regulatory requirements could emphasize the importance of generating data relevant to the older patients who constitute an increasing number of all patients with cancer in the U.S."
1. Green AK, Curry M, Trivedi N, Back PB, Mailankody S. Assessment of outcomes associated with the use of newly approved oncology drugs in Medicare beneficiaries. JAMA Netw Open. Published online February 24, 2021. doi:10.1001/jamanetworkopen.2021.0030
2. Melillo G. Pandemic brings racial, economic healthcare disparities into focus. Am J Manag Care. Published online April 6, 2020. Accessed February 24, 2021. https://www.ajmc.com/view/pandemic-brings-racial-economic-healthcare-disparities-into-focus