Immunotherapy for NSCLC Safe in Elderly Patients, but More Research Needed

Immune checkpoint inhibitors (ICIs) are safe as first-line treatment for advanced non–small cell lung cancer (NSCLC) in elderly patients, according to a new review published in ESMO Open that also highlights a need for the inclusion of this patient population in clinical trials and real-world analyses.

Although the use of ICIs has become the standard of care in advanced NSCLC, clinical trials often exclude the elderly population. 

“Since eligibility for pivotal clinical trials of first-line ICIs in NSCLC was conditioned by platinum eligibility, the elderly population is not well represented here, with patients ≥75 years of age being almost 10% of the overall population,” the authors wrote. “In addition, the age cut-offs used were different among clinical trials and no information is available on specific subsets of elderly patients included.” In clinical practice, more than 40% of patients with lung cancer are 70 or older.

In the elderly population, main concerns include potential treatment toxicities and age-related immune system changes that may affect therapy response. Considering elderly patients make up a significant proportion of those who may be eligible for first-line ICI monotherapy or combination therapy, it is crucial to explore the safety and efficacy of these treatments specifically among elderly individuals.

The review follows an expert panel discussion that took place during the 14th International Experts Panel Meeting by the Italian Association of Thoracic Oncology (AIOT), which was held virtually in July 2022. The panel reviewed the limited available evidence on first-line ICI-based regimens in elderly patients with NSCLC to produce a position paper with clinical practice and research suggestions.

The panelists concluded that age itself is not necessarily a limitation for treatment selection, but it should be considered as a surrogate for potentially important factors that may be age related, such as Eastern Cooperative Oncology Group performance status or comorbidities.

They also agreed that the data reviewed support overall ICI efficacy in the elderly population and that single-agent immunotherapy appears safe in this population. Chemotherapy in combination with immunotherapy, however, may pose additional safety risks that are mostly due to chemotherapy toxicities. Thus, combined approaches should be individualized to mitigate toxicities, the panelists concluded.

Regarding clinical research, the panel considered real-world assessments including elderly patients treated with ICIs to be a top priority, considering their historical underrepresentation in clinical trials of ICI-based treatment regimens.

“More in depth, they advocate the adoption of better data quality from real-world databases to be able to assess all the subsets in the elderly population, including frailty; comorbidities, which may impact tumor response; treatment efficacy; and tolerability with ICI-based regimens,” the authors wrote.

Considering the available data, ICIs were found to be effective in the elderly population, and single-agent immunotherapy was not found to have new safety signals in the review. The concerns surrounding combination regimens were particularly applicable to octogenarians, the authors noted.

“In this line, the panel experts agreed on the need to expand clinical research with robust real-world studies, and investigate alternative combination strategies with less toxic potential in the elderly patients with advanced NSCLC,” the authors wrote.

Reference

Gridelli C, Peters S, Velcheti V, Attili I, de Marinis F. Immunotherapy in the first-line treatment of elderly patients with advanced non-small-cell lung cancer: results of an International Experts Panel Meeting by the Italian Association of Thoracic Oncology (AIOT). ESMO Open. Pubished online March 23, 2023. doi:10.1016/j.esmoop.2023.101192