Gender Representation and Global Applicability of the HARMONi-6 Findings

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, to examine two of the most frequently discussed aspects of the HARMONi-6 trial: the overwhelmingly male study population and the fact that enrollment was limited to patients in China. As the panel evaluated the implications of the positive phase 3 results for ivonescimab plus chemotherapy in advanced squamous NSCLC, they emphasized the importance of determining whether the findings can be generalized to broader patient populations worldwide.

The panel largely agreed that the predominance of male patients should not be viewed as a major limitation of the study because it reflects the epidemiology of squamous NSCLC itself. Dr. Naidoo noted that although diversity and equitable representation remain important goals in clinical research, the gender distribution observed in HARMONi-6 closely mirrors the demographics commonly seen in patients with smoking-related squamous lung cancer globally. Dr. Wang echoed this perspective, describing the enrollment pattern as a feature of the disease rather than a flaw in the trial design. While both acknowledged that additional data in female patients would be valuable, neither identified a compelling biological rationale suggesting that treatment efficacy would differ substantially based on sex.

The panel devoted more extensive discussion to the study’s China-only enrollment and the broader question of whether the efficacy signal would translate to global populations. Dr. Naidoo emphasized that while regional differences in clinical trial conduct, toxicity reporting, and patient management may influence study outcomes, there is currently little evidence to suggest that squamous NSCLC behaves fundamentally differently across geographic regions. 

Dr. Wang similarly noted that the underlying biology of smoking-related squamous lung cancer is likely comparable worldwide, making it unlikely that major efficacy differences would emerge solely based on geography. At the same time, both panelists agreed that the ongoing global HARMONi-3 trial will be essential for confirming the generalizability of the HARMONI-6 findings and determining how the therapy performs across diverse patient populations and healthcare settings.