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Older Patients Left Behind in Progress Against Lung Cancer, Yale Study Shows

January 25, 2023

Although widespread use of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer has led to meaningful improvements in survival in younger patients, older patients have not experienced similar survival benefits, new research from Yale Cancer Center shows. The study was published in JAMA Oncology.

“There has been a great deal of excitement in the cancer community regarding the potential of immune checkpoint inhibitors to improve survival in patients with lung cancer,” said Teja Voruganti, MD, PhD, first author of the study. “The initial clinical trials that led to FDA approval for these treatments suggested impressive benefits. Now that these medications have been used in clinical practice for several years, it is critical to assess the survival benefits for patients in routine clinical practice, outside of the clinical trial setting.”

Prior work by senior author Cary Gross, MD, professor of medicine and of epidemiology (chronic diseases) at Yale, and his team, demonstrated that patients enrolled in initial clinical trials that led to FDA approval of ICIs are often younger and healthier than patients with cancer in “real world” clinical practice.

“It is unclear whether the substantial benefits that we see in pre-marketing trials of cancer therapies in fact bear out when the treatments are used in everyday practice,” Gross said. “That’s what patients care about — they’re not just asking ‘What did the initial study show?’ They want to know, ‘What happens when people like me take this treatment?’”

For the new study, the authors analyzed a large database of patients with advanced-stage lung cancer who were diagnosed from 2011 (which was prior to the discovery of ICI treatments) through 2019. They found that by the end of the study period, there was no difference in the use of ICIs between younger patients (age 55 and younger) and older patients (age 75 and older); Just under half of the patients in each group were receiving ICIs. But the effect on survival outcomes differed dramatically: After ICIs were approved in 2015, survival increased from 11.5 months to 16 months among younger patients in 2019. However, in older patients the median survival increased from 9.1 months to 10.2 months over the same time interval. Notably, this is below the 2-3 month threshold for clinical benefit that the American Society of Clinical Oncology has defined as a “clinically meaningful” survival improvement for lung cancer.

Not only have ICIs opened new avenues of treatment in many different cancers, but the side effects of ICIs are often more well-tolerated than traditional chemotherapy. However, Gross cautions, “Any cancer treatment has a cost. Estimates of the cost of Pembrolizumab, one of the ICIs used to treat advanced lung cancer, can be over $100,000 annually. Therefore, we need to critically look at the benefits of these treatments in our patients.”

"The use of immune checkpoint inhibitors has been touted as a 'game changer' in the treatment of lung cancer, but our findings show that the impact on older adults may not actually be clinically meaningful," Gross added. “This is a wake-up call for patients, researchers, and policy-makers: We need to determine which cancer treatments are effective in older patients, rather than relying on assumptions. These are life and death questions — we need evidence."

Other team members included: Pamela Soulos, MPH, associate director of the COPPER Center at Yale School of Medicine; Ronac Mamtani, MD, from the Abramson Cancer Center at the University of Pennsylvania; and Carolyn Presley, MD, at Ohio State University Comprehensive Cancer Center/James Cancer Hospital and Solove Research Institute.

Submitted by Emily Montemerlo on January 26, 2023