Veterans often have characteristics and comorbidities that can make them less likely to be included in clinical trials.
Military veterans tend to be older, more frail, and have more comorbidities compared with the general population. Those characteristics and others mean it can be particularly difficult to treat veterans who have received an advanced lung cancer diagnosis.
In a new review article published in Seminars in Oncology, the authors describe the unique issues related to patient management of veterans with advanced lung cancers. They noted that the very factors that make veterans difficult to treat also make many clinical trials less applicable to this population, since many trials exclude patients with significant comorbidities or frailty. This puts the onus on physicians to take a very individualized approach to care.
Management starts with assessment of patient frailty, the authors said. However, there are multiple frailty indexes to choose from, and the lack of consensus on how to assess frailty can make it difficult to compare outcomes. The investigators said providers should seek out risk assessment tools that are suitable for their own particular situations and resources, as age alone is not a substitute for frailty. Better research is needed into frailty and its effects on patient outcomes, they emphasized.
“Studies focused on older frail individuals are needed to assess both tolerability and outcomes of modern therapeutics in this population, to better inform shared decision-making and cancer management,” they wrote.
The authors next evaluated types of systemic therapy. They said cytotoxic chemotherapy can be challenging for this patient population. Sometimes, the most effective therapy is not a good fit for frailer patients.
“For example, the addition of carboplatin to pemetrexed in older patients with performance status ECOG [Eastern Cooperative Oncology Group scores] of 0-2 improves survival but is associated with increased toxicity (including treatment-related deaths),” they noted.
For patients with higher levels of impairment, such as ECOG 3-4, best supportive care is likely the best option, they said.
Some targeted therapies appear to be tolerable and effective in older patients, although the investigators said there is a “paucity of data” on targeted treatments for older patients in the clinical literature. In addition, even though some of the existing data are positive, the investigators said many clinicians do not complete the genetic testing on older patients that would be required to prescribe targeted therapies.
They noted that in 2016, the Veterans Health Administration launched a program aimed at increasing next-generation sequencing (NGS) in veterans with cancer. Still, nearly one-third of the veterans in the program with non–small cell lung cancer did not end up receiving targeted therapies.
“The most common reasons were that patients did not have metastatic disease (33.3%), the treating provider did not comment on the NGS results (25%), or the provider felt that the patient could not tolerate therapy (19.4%),” the authors said.
As with targeted therapies, the investigators said data are lacking on the impact of immunotherapy on older patients with lung cancer. They noted that the landmark trials used to evaluate anti–programmed cell-death protein 1 and anti–programmed death-ligand therapies only included patients with excellent performance statuses. However, what research exists into older and frail patients indicates that patients with good performance statuses can safely and effectively be treated with immunotherapy.
“These findings suggest that patients should not be excluded from consideration of immunotherapy based on age alone,” they said.
The investigators said veterans with comorbidities should be carefully monitored during cancer treatment. They noted, for instance, that veterans are at a much higher risk of cardiovascular events during and after cancer treatment compared with age- and gender-matched controls. Liver, kidney, and pulmonary diseases are also common in this patient population and therefore pose a significant treatment challenge.
The authors closed with a discussion of the need for future research that more closely evaluates lung cancer therapies in older, more frail patients such as veterans. They noted that the Department of Veterans Affairs has launched a lung cancer precision oncology program, which they said provides a “unique opportunity” to generate studies of this population.
“We hope that the above discussion will stimulate a needed discourse on improving the evaluation and management of elderly and frail cancer patients through thoughtfully designed trials,” they wrote. “Results obtained in US veterans in these categories will also inform the care of the broader general population.”
Reference
Thomas T, Patel B, Mitchell J, Whitmer A, Knoche E, Gupta P. Treating advanced lung cancer in older veterans with comorbid conditions and frailty. Semin Oncol. Published online July 3, 2022. doi:10.1053/j.seminoncol.2022.06.004
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