Postprogression Therapy Access May Confound OS Benefit in Trials

In an interview, Daniel Araujo, MD, of the University of Florida, discussed a cross-sectional analysis examining whether inconsistent control-arm access to effective postprogression therapies may be confounding overall survival (OS) results in first-line oncology trials.

Araujo explained that the study was prompted by a structural quirk in oncology drug development: agents are typically proven effective in later lines before being tested in the first-line setting. When a first-line trial is read at face value, he noted, it is not always clear whether the control arm ultimately received that same agent—an issue complicated by international trials, where standard-of-care access varies by country.

The analysis, a proof-of-concept cross-sectional study, screened top-tier journals for 52 phase 2/3 randomized trials of first-line targeted therapy (TT), immune checkpoint blockade (ICB), or hormone therapy in advanced lung, breast, or prostate cancer, restricted to agents with established OS benefit in later lines.

Only 65% of control-arm patients received any subsequent therapy at all, Araujo said, a figure he called lower than expected. That proportion dropped to 42% when limited to the investigational agent or a similar-class drug. No overall correlation emerged between post-progression access and OS hazard ratio across all trials. However, a subgroup analysis showed a positive correlation specifically within TT trials, suggesting that some of the survival benefit attributed to first-line use may instead reflect control-arm patients never receiving the agent at all. No such association appeared in ICB trials, hinting that timing of immunotherapy access may matter more than it does for targeted or hormone therapy—though Araujo cautioned this remains hypothesis generating.

Looking ahead, Araujo said the group plans to expand the dataset to additional TT trials to validate these findings. He emphasized that trials should report post-progression access consistently, and that the oncology community should advocate for standardized access to standard-of-care therapies to better assess whether first-line timing truly matters.

REFERENCE

Apolinário et al. Impact of access to effective post-progression therapies on survival outcomes in first-line randomized oncology trials. J Clin Oncol. 44, 1500-1500(2026). doi:10.1200/JCO.2026.44.16_suppl.1500