Transforming Cancer Care Through Patient-Centered Research

ACT: How can we transform cancer care through more patient-centered research and treatment analysis?

Buyse: Just building on what Sebastien just mentioned, the fact that by looking at the benefit-risk of a treatment, rather than just the benefit, and then looking at the risk as a secondary type of endpoint, we look at the benefit-risk again as a holistic view of the treatment. That really changes the way we look at cancer treatments, especially as viewed from the patient perspective, because the patient will worry both about the efficacy of the treatment, of course; does it improve my outcome? Does it prolong my survival? Does it make my quality of life better? But also, about the side effects and in oncology, as we know, the side effects sometimes are really, really bothersome to the patients, to the extent that many patients actually stop taking their treatments simply because the side effects are too bothersome. And in advanced disease, it's even worse, sometimes patients in advanced disease prefer not to be treated at all, because they know that their prospect in terms of duration of survival cannot be improved very much, and they prefer to live a shorter time, but in very good quality of life, rather than being submitted to long, prolonged treatments that have horrible toxicities. So it's a difficult trade off, but it's the patient view. And to come back to the choice of the dose of a treatment, for too long, the paradigm in oncology was to give the maximum tolerated dose. So when cytotoxic drugs were developed, the idea was to push the dose up to reach toxicity, and then toxicity was used as a surrogate for efficacy. A patient who had toxicity was a patient who might benefit from the treatment, because the anti-tumor effect was really very strong in that patient. Now, that has given very good results, but it has also resulted in a lot of toxicities being imposed on patients, when in fact, a lower dose might have had a very similar efficacy, but much less toxicity, and that has been acknowledged by the agencies, especially by the FDA. The FDA, as you may know, has a project called Project Optimus, and the goal of Project Optimus is to try to better identify the dose that has the best benefit-risk ratio. So, exactly using the approach that we advocate, which is to look at the benefit-risk ratio instead of focusing only on the efficacy of a drug. So we believe again, that the generalized pay wise comparison, which is the technical name of the method we use, that approach, has a lot of potential to compare different doses of the same drug in terms of the benefit-risk of these different doses. And that's what matters, not just the efficacy, not just the safety, but the combination of both.