• 03 OCT 18
    • 0

    Changing Lung Cancer Clinical Trial Design in the Era of Precision Medicine and Immunotherapy

    Chemotherapy has been the standard treatment for advanced non-small cell lung cancer, or NSCLC, for a long time. But with recent advances in molecular and genomic techniques, tremendous progress has been made in the treatment of the cancer. Discovery of immune checkpoint inhibitors has helped to release the power of the body’s immune system to attack and fight the lung cancer, while the discovery of driver gene alterations has ensured a more targeted cancer treatment in many patients.

    “In the era of precision medicine and immunotherapy, cancer therapy has benefited tremendously from leveraging advances in other areas to improve outcomes,” said Dr. Steven E. Finkelstein, director at Bay Regional Cancer Center. “As oncologists, we can now harness the best of these technologies to deliver the best care possible to our patients.”

    Impacts on the design of clinical trials

    These developments also have had a huge impact on how clinical trials for cancer are designed and executed. While it was previously possible to compare minor cytotoxic changes in larger chemotherapy clinical trials for NSCLC, that’s no longer possible. Instead, a clinical trial now must be designed with a clear partitioning of cancer patients into narrower, more precise and selective populations.

    “Clinical trials have had to evolve speedily in order to deliver useful outcomes in this exciting era of immunotherapy,” said Dr. Finkelstein. “Each has to identify a unique population to work with and must go beyond the formerly common approach of working with randomized populations in every trial.”

    The randomized clinical trial (RCT) has been the gold standard for a long time and has been trusted to effectively evaluate new cancer treatments. However, because it relies primarily on disease-specific survival and overall survival after treatment as core indicators for efficacy of a new treatment, RCT may provide positive results in larger studies not because of a treatment’s clinical impact but only because the treatment has a statistical impact.

    Another weakness of RCT is that it can miss its targeted endpoint due to lack of a definite molecular profile for the necessary response in patients with the tumors under investigations. And even if such molecular profiles are available, their large number implies a need for greater technical stratifications, which can make clinical trials too costly and impractical.

    What should new lung cancer clinical trials include in their design?

    “New lung cancer trials should include surrogate endpoints in order to reduce dependence on patient survival as the only endpoint,” said Dr. Finkelstein. “For instance, biomarkers can be used as alternatives to the standard RCTs. With the use of biomarkers, evaluation of new therapies can be quicker and more certain, which may help with the approval of any relevant new targeted agents.”

    Studies with known immediate endpoints should be used to optimize patient selection, hasten molecular stratification for every trial and overcome the obstacles of randomized trials. Likewise, it is easier to know the number of patients to include in studies with improved endpoints. Such studies can deliver results quickly, help reduce the adverse events linked to larger and lengthier RCTs, diminish patient suffering, produce new treatments faster and identify efficacious treatments better than randomized studies.

    How has the use of immune checkpoints improved clinical trials for lung cancer?

    Immune checkpoint inhibitors have improved the treatment of several cancers, including NSCLC. Many such immune checkpoint inhibitors are now available as second-line treatment for advanced NSCLC, while pembrolizumab is available as a frontline treatment for advanced NSCLC with 50 percent PD-L1 expression or higher and lack ALK or EGFR mutations. For this reason, the testing of PD-L1 expression has become routine at diagnosis for advanced NSCLC patients.

    “Several clinical trials now include targeted therapy and molecular testing in their design as treatment options for unique groups become available,” said Dr. Finkelstein. “In fact, various clinical trials are now using ALK or EGFR inhibitors or nivolumab for patients having resected early-stage NSCLC.”

    Several basket trials have tested various targeted therapies using different designs and achieved positive outcomes. One such clinical trial design involves testing a single targeted drug tested across several types of tumors. For example, the clinical trials of the drug vemurafemb has been tested across multiple non-melanoma cancers with BRAF mutations.

    “During these trials vemurafemb showed a histiocytic activity and was confirmed effective in BRAF-mutated NSCLC, resulting in the approval of BRAF inhibitors for treatment of advanced NSCLC,” said Dr. Finkelstein.

    Several drugs were applied across many different types of tumors in two other basket trials. These large trials used a multi-drug, targeted screening methodology to match patients in a single multiple trial and to substitute and investigate different drugs in one trial. The outcomes were positive and quick, indicating the need for more clinical trials to adopt immune checkpoints.

    At Bay Regional Cancer Center, we are engaged in continuous research to improve the treatments we offer to our patients. That’s why we are incorporating immune checkpoints in our clinical trials to ensure that we get reliable outcomes faster and are able to apply the latest treatments in caring for our patients. So when treated at BRCC, you can be sure that you’ll have access to the most advanced treatments for your condition. For more information on cancer treatment and our latest clinical trials, visit the “Bay Regional Cancer Center” site.