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Does stronger initial response to cancer treatment predict longer overall survival?

August 14, 2017

Robert C. Doebele, MD, PhD
It seems like such a simple question: Do patients whose tumors shrink more in response to targeted treatment go on to have better outcomes than patients whose tumors shrink less? Actually, the answer seems simple too. In short, the answer is yes – a deeper initial response leads to a longer overall response. But the implications of a recent study demonstrating this relationship are anything but simple and could influence both the design of future clinical trials and the goals of oncologists treating cancer.

In the context of clinical trials, the good news is that better medicines are leading to longer survival. But a byproduct of longer survival is more time needed to complete trials. It makes sense: The longer that patients live, the longer trial designers must wait to see how long patients will live. One adaptation to this fortunate reality is that rather than using overall survival (OS) as the measure of a drug’s success, many clinical trials now use a kind of midpoint, namely progression-free survival (PFS) – the time that it takes for a tumor controlled by the trial’s medicine to restart its growth.

However, with newer drugs even PFS may require a long wait. For example, the drug crizotinib approved to treat ALK-positive lung cancer, showed a PFS of 10.9 months. Now the next-generation ALK-inhibitor, alectinib, shows PFS of nearly 25 months. Waiting for PFS may slow the availability of important new medicines to treat the condition.

“For someone to go up against alectinib, it would be nice to know earlier if there might be an improvement,” says Robert C. Doebele, MD, PhD, investigator at the University of Colorado Cancer Center and associate professor of Medical Oncology at the CU School of Medicine.

The current study suggests that just as PFS can be used as a proxy for OS, depth of response may be a proxy for PFS. In other words, if depth of response hints at overall survival, then maybe depth of response could be an early sign that an investigational drug is working.

In addition to offering early evidence of a drug’s effectiveness, if depth of response predicts patient outcomes, then, Doebele says, depth of response may be a useful goal of treatment.

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