HARMONi-6 / NSCLC 06/21/2026

Age-Related Findings and Subgroup Analyses From the HARMONi-6 Trial

A smiling oncologist in a white lab coat with a blue and purple striped tie, sitting in a clinical laboratory environment, representing cancer research and treatment. Benjamin Levy, MD Confident professional woman smiling with arms crossed in modern office environment, representing leadership and success in the workplace. Jarushka Naidoo, MB, BCh, MHS Young professional man in a dark suit and glasses smiling outdoors with a blurred green background, representing confidence and professionalism. Bo Wang, MD

Key Points

  • The exclusion of patients older than 75 years was identified as an important consideration, but the panel viewed it as a question for future study rather than a major limitation of HARMONi-6.
  • Experts cautioned against overinterpreting the apparent lack of overall survival (OS) benefit among patients aged 65 years and older, noting that subgroup analyses are not powered to provide definitive conclusions.
  • The strongest subgroup signal appeared among patients with PD-L1–negative disease, reinforcing the potential value of dual PD-1 and VEGF inhibition across a broad range of patients with squamous non-small cell lung cancer (NSCLC).

Benjamin P. Levy, MD, of Johns Hopkins Sidney Kimmel Cancer Center, was joined by Jarushka Naidoo, MB, BCh, MHS, of Beaumont RCSI Cancer Centre, and Bo Wang, MD, of Willamette Valley Cancer Institute and Research Center, for a discussion of several important subgroup analyses from the phase 3 HARMONi-6 study. The conversation focused on the implications of excluding patients older than 75 years, the interpretation of age-related efficacy findings, and what can realistically be learned from subgroup analyses evaluating outcomes with ivonescimab plus chemotherapy in advanced squamous NSCLC.

The panel agreed that the exclusion of patients older than 75 years represents a limitation that should be considered when interpreting the data, although they noted that age restrictions of this type are more common in certain regions, including China. Dr. Naidoo emphasized that concerns regarding treatment efficacy or toxicity in older patients have frequently emerged during the development of new oncology therapies, only to become less significant as larger datasets and real-world experience accumulate. 

Dr. Wang further noted that ivonescimab has already been used extensively in China, creating an opportunity for future real-world evidence to help address unanswered questions regarding outcomes in elderly patients. Both panelists viewed age as an area requiring further study rather than a major concern that diminishes the overall positive findings of the trial.

The discussion also explored the subgroup analysis showing less apparent OS benefit among patients aged 65 years and older. Both Dr. Wang and Dr. Naidoo cautioned against overinterpreting these findings, emphasizing that the study was not powered to detect differences within individual subgroups and that factors such as disease burden, treatment exposure, comorbidities, and toxicity may have influenced outcomes. 

In contrast, the panel highlighted the consistent efficacy signals observed across most other patient subsets, particularly among patients with PD-L1–negative disease, where the magnitude of benefit appeared especially compelling.