Daniel Vilarim Araujo, Medical Oncologist at BC Cancer, shared on X:
”Proud to share work from our group at ASCO26 (Abstr 1500, oral). Shout-out to first author João Pedro Apolinário and Vladmir Cordeiro de Lima for co-leading this project!
The question
Do OS benefits in first-line RCTs partly reflect lack of access to effective subsequent therapies in the control arm – rather than the value of moving the drug earlier?
What we did
Cross-sectional analysis of 52 phase II–III RCTs (2010–2025, high-impact journals) of first-line targeted therapy (TT), immune checkpoint blockers (ICB), or hormone therapy in advanced lung, breast, or prostate cancer, where the investigational agent had a known OS benefit in later lines. We quantified the % of control-arm pts who later accessed the investigational drug (or similar class) and correlated this with the OS HR.
What we found
Across all trials, no overall correlation between post-progression access and OS HR. But in TT trials, higher control-arm access to effective subsequent therapies correlated with a smaller OS benefit (r = 0.44–0.46), with no such signal for ICB.. Post-progression access was lowest in breast, then prostate, then lung.
My take
The TT signal suggests that at least part of the OS benefit attributed to first-line TT may potentially reflect lack of access to effective drugs later in the control arm, rather than the value of giving the drug upfront.
Speculative, but the TT-vs-ICB divergence is intriguing – possibly related to TME changes after initial systemic therapy, supporting the idea that ICIs should be offered earlier in the disease course (DREAMseq in melanoma is consistent with that).
Globally, SOC access in later lines varies enormously by country and health system. We strongly advocate for broader access to SOC therapies in subsequent lines for pts with metastatic cancer – and for trials to standardize how they report it.
Looking forward to João Pedro presenting!”
Title: Impact of access to effective post-progression therapies on survival outcomes in first-line randomized oncology trials.
Author: Daniel Vilarim Araujo
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