Survival gains with checkpoint inhibitors differ ‘drastically’ between age groups in NSCLC
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Despite significantly extending survival for younger adults with advanced non-small cell lung cancer, immune checkpoint inhibitors have conferred only modest OS gains over time among patients aged older than 75 years, study results showed.
The increase of slightly more than a month in median OS among older adults who received immune checkpoint inhibitors since the FDA approved their use in 2011 does not meet the definition of a clinically meaningful benefit based on ASCO guidance, the investigators noted.
Adoption of immune checkpoint inhibitors following their commercial approval occurred at an equally rapid pace regardless of age strata among adults with NSCLC, according to Cary P. Gross, MD, professor of medicine and public health at Yale School of Medicine.
“But the improvement in survival over time was drastically different,” he told Healio.
“Considering the full sample of patients with lung cancer, there was a substantial improvement in survival over time in younger patients — you could say that the ‘immunotherapy era’ was associated with significant survival benefits,” Gross said. “But that wasn’t the case in the oldest patients, where overall changes in survival were minimal.”
Background
Older adults are more frequently diagnosed with cancer while often being excluded from clinical trials for new therapies, making evaluations of how these treatments perform in real-world practice essential to determining their value for older patients, Gross noted.
“Given that the older population is frequently underrepresented in clinical trials, we wanted to analyze what changes were occurring in lung cancer treatment over the past decade,” he said. “This was particularly important for lung cancer, because there have been so many exciting developments in new treatments over the past decade.”
Methodology
Gross and colleagues conducted a prospective cohort study to evaluate age-based temporal trends in immune checkpoint inhibitor use and survival among patients with advanced NSCLC.
The multicenter analysis included 53,719 patients (mean age, 68.5 ± 9.3 years; 52.8% men; 67.6% white) aged 18 years or older diagnosed with stage IIIB, stage IIIC or stage IV NSCLC between Jan. 1, 2011, and Dec. 31, 2019, at one of 280 community-based cancer clinics in the United States included in the nationwide Flatiron Health electronic health record-derived deidentified database.
Median OS and 2-year survival probability served as the study’s primary outcome measurements.
Key findings
The analysis found a significant increase in use of immune checkpoint inhibitors during the study period, ranging from 4.7% in 2015 after their first approved indication for NSCLC to 45.6% in 2019 (P < .001).
The investigators also noted similar rates of immune checkpoint inhibitor use among adults aged 55 years or younger and those aged 75 and older (45.2% vs. 43.8%).
Median OS in patients younger than 55 years increased from 11.5 months to 16 months from 2011 to 2018. Meanwhile, median OS increased from 9.1 months to 10.2 months among patients 75 years and older during the same timeframe.
Between 2011 and 2018, the predicted probability of 2-year survival significantly increased from 37.7% to 50.3% among adults aged younger than 55 years compared with a more modest increase from 30.6% to 36.2% among those 75 years or older (P < .001).
Clinical implications
Given the lack of a clinically meaningful survival benefit among older patients with NSCLC in his group’s study, Gross said more trials designed with a focus on these patients are needed.
“It is not clear whether treatments that work in the younger population are effective in older patients,” he told Healio, adding that patients should be made aware of this by their treating physicians.
“We are in unchartered territory when it comes to decision-making for our oldest patients,” Gross said. “There is so much uncertainty, and our patients are looking for help.”
The findings by Gross and colleagues are important because they suggest an inverse association between age group and survival among those who received immune checkpoint inhibitors for NSCLC, according to Marjory Charlot, MD, MPH, professor of medicine and medical oncologist at The University of North Carolina Lineberger Comprehensive Cancer Center, and Jhanelle E. Gray, MD, program leader and senior member for thoracic oncology at Moffitt Cancer Center.
The results are informative because the greatest gains in survival occurred among younger adults despite a median age of 71 years for those diagnosed with lung cancer, Charlot and Gray noted in an accompanying editorial.
“The findings ... may help inform shared decision-making discussions in clinical practice, particularly for the oldest adult age group with NSCLC. The inclusion of older and diverse patient populations in clinical trials is important to improve their access to cutting-edge treatments and to improve generalizability of study results,” Charlot and Gray wrote. “Although data on PD-L1 expression level and performance status were not included, this study still represents an important step in defining clinically meaningful benefits of [immune checkpoint inhibitors] in clinical practice across all age strata.”
References:
- Charlot M, et al. JAMA Oncol. 2023;doi:10.1001/jamaoncol.2022.6867.
- Voruganti T, et al. JAMA Oncol. 2023;doi:10.1001/jamaoncol.2022.6901.
For more information:
Cary P. Gross, MD, can be reached at Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale School of Medicine, 367 Cedar St., New Haven, CT 06520; email: cary.gross@yale.edu.
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