Researchers analyze efficacy and toxicity of ICIs in older patients with NSCLC

Older adults with advanced non-small cell lung cancer (NSCLC) may be particularly vulnerable to adverse events, therapy discontinuation, glucocorticoid rescue, and hospitalization during treatment with immune checkpoint inhibitors (ICIs), according to a recent study published in the Journal of the American Geriatrics Society.

“NSCLC is predominantly a disease of older adults; 50% of all lung cancer diagnoses and NSCLC-related deaths occur in patients older than 70 years,” wrote Eugene Muchnik, MD, James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, and colleagues.

In recent years, ICIs have changed the landscape of cancer treatment, yet surprisingly little is known about their effects in the elderly due to a general underrepresentation of this population in clinical trials.

“Patients older than 65 years made up 31.7% to 41.0% of clinical trial participants, despite the fact that 60.6% to 64.0% of patients with NSCLC receiving ICIs in clinical practice are older than 65 years. In the CheckMate 017 and 057 trials, for example, only about 30% of the study population was aged 64 to 75 years, and 8% were older than 75 years. In addition, older adults who are enrolled in clinical trials are typically fitter than the general geriatric oncology population seen in routine clinical practice,” the researchers added.

Of particular concern is the possibility that ICIs may be less effective in the elderly due to naturally occurring immunosenescence.

Dr. Muchnik and colleagues, therefore, undertook this retrospective, real-world study to determine the efficacy as well as toxicity of ICIs in 75 older patients (aged ≥ 70 years) with advanced NSCLC who were seen in routine clinical practice. Most patients were treated with nivolumab (87%), and most received ICI treatment in the second-line setting (69%), with treatment initiation at a mean age of 74 years.

In all, 53% of patients had a Charlson Comorbidity Index (CCI) score of ≥ 3 (mean CCI: 2.7), and 49% had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of ≥ 2.

Roughly 8 months into follow-up, a full 71% of patients had died. Median overall survival was 8.2 months, and was longer in patients with an ECOG PS score of 0-1 compared with a score of ≥ 2 (13.7 vs 3.8 months, respectively; P < 0.01). One-year survival was significantly higher in patients with an ECOG PS score of 0-1 as well (60% vs 21%). Finally, median time to treatment failure was 4.2 months, and again, was higher in those with an ECOG PS score of 0-1, compared with ≥ 2 (5.6 vs 2.0 months; P=0.02).

No patients exhibited a complete response to treatment, while 36% achieved partial response.

A full 37% of patients experienced immune-related adverse events (irAEs) of any grade, for a total of 37 events. Of these, 8% were ≥ grade 3. No deaths related to ICIs occurred. Among patients with irAEs, 64% required systemic glucocorticoid treatment.

Sixty-four patients discontinued ICI treatment (85%), with 15% due to irAEs and 60% due to disease progression. Dose delays or interruptions were recorded in 47% of patients. A full 72% of patients were hospitalized during ICI treatment.

 “Outcomes in our cohort were driven by ECOG PS rather than chronological age or comorbidities. The relatively high rates of ICI discontinuation, use of glucocorticoids, and hospitalization during ICI treatment in our study highlight the vulnerability of older adults with advanced NSCLC even in the immunotherapy era,” noted Dr. Muchnik and colleagues.

“Given the established utility of the geriatric assessment (GA) and the increased risk of toxicity as demonstrated by our study as well as others, further study on GA in the setting of ICIs is needed to identify patients with low physiologic reserve who are at risk of experiencing functional decline and death from ICIs,” they concluded.

This study was funded by the Wilmot Cancer Institute Geriatric Oncology philanthropy fund and a Wilmot Cancer Institute Fellowship.