Postprogression Access to Effective Targeted Therapy Tied to OS Benefit

According to results from a cross-sectional analysis of 52 phase 2/3 randomized trials, only 42% of control-arm patients across first-line oncology trials received an effective postprogression therapy. Higher postprogression access to such therapy was moderately associated with a smaller overall survival (OS) benefit in trials of targeted therapies but not in trials of immune checkpoint blockers (ICB).

Across the 52 included trials, published between 2010 and 2025 in high-impact journals, a mean of 66% (SD, 14%) of control-arm patients received any postprogression therapy, though only 42% (SD, 22%) received an effective agent from the same class as the drug under investigation—equivalent to 62.5% in relative terms. Postprogression access to effective therapy differed significantly by tumor type (P <.001), with the lowest rates observed in breast cancer, followed by prostate and lung cancer. The median proportion of patients enrolled outside the United States and Europe was 36%, and the overall median HR for OS across trials was 0.78.

Study Design

Investigators led by Daniel Araujo, MD, a genitourinary medical oncologist at the University of Florida, conducted a cross-sectional, proof-of-concept analysis of first-line phase 2/3 randomized trials in advanced lung, breast, and prostate cancer in which the experimental arm evaluated a targeted therapy, ICB, or hormone therapy that had already demonstrated an OS benefit in later lines of therapy. Postprogression access to effective therapy was defined 2 ways: the proportion of control-arm patients who went on to receive the investigational agent or a drug of the same class relative to all patients randomized to the control arm (Ratio_Effective/Control), and relative only to patients who received any subsequent treatment (Ratio_Effective/Therapy). Investigators then assessed the correlation between each ratio and each trial's reported HR for OS, with prespecified subgroup analyses by treatment class and tumor type.

"The way that we develop drugs in oncology, we typically test agents later down the line, after the second or third line, when not too many options are available, and once drugs are proven to be efficacious, we bring them to the first line. So when we're reading a first-line trial, we are truly looking at first line vs the standard of care. However, there's a caveat: Has the patient received the drug that's been tested or not? Because if not, it's truly testing first line vs never receiving [the drug] at all,” Araujo said in an interview with Targeted Oncology^TM.

Key Findings

Of the 52 trials meeting inclusion criteria, control-arm patients received any postprogression treatment in a mean 66% of cases—lower than investigators anticipated.

"That was a little striking, because we were expecting higher numbers for any treatment at all. When we look at efficacious subsequent treatment—the drug being tested in first line, or one of its kind—that number drops to 42%, so a significant proportion of patients do not receive access to the drug being tested, and obviously this has implications down the line,” Araujo said.

No global correlation was observed between the rate of postprogression access to effective therapy and the HR for OS across all 52 trials. In targeted trials specifically, however, higher postprogression access to effective treatments was moderately associated with a less pronounced OS benefit (r =.44; P =.056 for Ratio_Effective/Control; r =.46; P =.046 for Ratio_Effective/Therapy). No such association was observed in trials evaluating ICB, and the difference in correlation between targeted therapy and ICB trials reached statistical significance (P =.032). No correlation was observed between the ratio of effective therapies and either tumor type or enrollment outside the US and Europe.

“This suggests that some of the benefit we see in survival in these first-line trials is truly derived from the fact that patients in the control group don't receive that drug at all. It was interesting because this was class specific, so it also suggests that potentially for immunotherapy, it does make a difference to receive it sooner rather than later—though not so much for targeted therapies and hormone therapies. But obviously, this is hypothesis-generating only,” Araujo said.

Clinical Context and Limitations

Araujo noted that international trials complicate interpretation of first-line comparisons because standard-of-care access to a given drug class varies substantially by country, and a meaningful proportion of patients never receive it regardless of trial arm. Investigators characterized the analysis as a proof-of-concept study and plan to expand the data set to additional targeted therapy trials to validate the findings in a larger sample.

"With international trials, we know that standard of care varies by country, and a significant proportion of patients don't receive this standard drug at all. I think the key message is that this is crucial information that is not reported consistently in trials. As an oncology community, we should advocate for patients receiving that standard of care treatment, and that standard of care needs to be similar depending on the country, so we can truly assess if it makes sense to give the drug in the first line or if it's equivalent to receive the drug at any time point in their cancer trajectory,” Araujo said.

REFERENCE
1. Apolinário JP, Araujo DV, Nohmi RL, et al. Impact of access to effective post-progression therapies on survival outcomes in first-line randomized oncology trials. Presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL. Abstract 1500. Accessed August 12, 2026.