Alice Shaw, MD, PhD, is a world-class thoracic oncologist at Massachusetts General Hospital and Harvard Medical School who focuses her research and her clinical practice on improving outcomes for patients with lung cancer. Her work, which often involves clinical trials, has been instrumental in the FDA approval of three treatments for ALK-positive lung cancer: crizotinib, ceritinib, and alectinib. Dr. Shaw recently spoke with LUNGevity to share her advice for patients and offer her answers to the common questions surrounding clinical trials.
LUNGevity Foundation: What advice do you have for patients who are newly diagnosed with advanced-stage lung cancer?
Alice Shaw: I recommend that all newly diagnosed patients have biomarker testing for gene mutations that may be driving the growth of their cancer. At the minimum, lung cancer specimens should be tested for EGFR, ALK, and ROS1 biomarkers, for which we have validated targeted therapies. But ideally, specimens should undergo multiplex testing, in other words testing for mutations in many different potentially targetable genes. In addition to gene mutation testing, patients should undergo testing to determine the level of the PD-L1 marker. For those patients without EGFR, ALK, or ROS1, but with high levels of PD-L1, the immunotherapy drug pembrolizumab has been shown to be more effective than chemotherapy. While the initial workup and diagnosis can be very stressful and overwhelming, I often encourage newly diagnosed patients to consider both standard treatments (ones that their oncologist can prescribe) and clinical trials, as trials may provide them access to even more effective first-line treatments.
LF: Do patients sometimes hesitate about participating in a clinical trial? Why do you think that happens?
AS: Patients are not always open to the idea of clinical trials. Over the years, I have heard various reasons for their hesitation, including the worry that they will be “treated like a guinea pig” or that “they will be experimented upon.” But I feel this is the wrong way to look at clinical trials. Certainly, in clinical trials, we are testing experimental therapies, sometimes for the very first time in patients. The trials often initially focus on establishing safety and dosing of a new drug, but we are also always looking for signs of clinical activity. I often remind patients that these trials may be the best (and only) way to access some of our most promising therapies in development.
LF: Are there any other common misconceptions about clinical trials?
AS: Many patients are worried about getting the “placebo pill,” and not receiving any treatment for their cancer. Early-phase studies (phase 1 and most phase 2) involve all patients receiving the experimental therapy. More advanced phase 3 studies are designed to test whether the experimental therapy is better than the current standard of care, and often involve randomization of patients to either an experimental therapy group or a “control” group. Unless the standard of care is to receive no treatment, patients who are randomized to the “control” group will always receive at least standard of care treatment. These studies help establish the efficacy of the new drug as compared to what we currently use. Overall, these clinical trials are very important because they allow researchers to develop new and more effective treatments—new standards of care—for patients everywhere.
LF: How do scientists set up clinical trials without placebos?
AS: There are many different ways to design clinical trials. Early-phase studies typically involve testing different doses of an experimental therapy and observing side effects. All patients in these early-phase studies receive the same drug, albeit possibly at different doses or schedules. Many phase 2 studies are “single arm” studies, meaning that all patients receive the same drug and typically at the same dose. In these studies, the focus is both efficacy and safety of the new drug. Phase 3 clinical trials will typically have one set of patients who receive the current standard of care and another set of patients who receive the new treatment. This type of study allows us to determine whether the new therapy is better than the standard of care treatment. But no matter what type of clinical trial, the end goal is always the same: to find new treatments that help patients live longer, better lives.
Dr. Shaw is a member of LUNGevity Foundation’s Scientific Advisory Board. She is also Director of the Center for Thoracic Cancers at Massachusetts General Hospital and an Associate Professor of Medicine at Harvard Medical School.
Juhi Kunde, MA, is a science writer for LUNGevity.