Checking Out Emerging Approaches in Lung Cancer Treatment in Chicago

We recently traveled to Chicago, Illinois for a State of the Science Summit™ on Lung Cancer. At the meeting, faculty from the University of Chicago emphasized the impact of immunotherapy in non—small cell lung cancer, including the paradigm shift in the treatment of patients with stage III disease, promising combinations under exploration in stage IV nonsquamous disease, and key updates with the approach in stage IV squamous disease. Other topics included promising agents that are accelerating advances made in the treatment of patients with ALK- and ROS1-positive disease, updates with targeted therapies in patients with molecular aberrations, and game-changing management approaches that have emerged in small cell lung cancer.

First, we spoke with the chair of the meeting, Jyoti D. Patel, MD, FASCO, a professor of medicine and director of Thoracic Oncology at the University of Chicago Medicine. Patel told us that the use of immunotherapy in the frontline has led to tremendous benefit in patients with advanced nonsquamous NSCLC, but these therapeutics should only be given in the absence of a driver mutation. Determining whether a patient has a genotypic driver present up front will inform whether to proceed with immunotherapy or a targeted therapy, explained Patel. In our interview, Patel outlined what the current treatment paradigm looks like for patients with stage IV nonsquamous NSCLC, stressed the importance of genetic testing prior to the start of immunotherapy, and outlined key trials that have impacted the space.

Speaking to the updates reported with the use of immunotherapy in patients with stage IV squamous NSCLC was Christine Bestvina, MD, a thoracic oncologist from the University of Chicago. In our interview, Bestvina highlighted some of the new options available for the treatment of squamous cell carcinoma of the lung, particularly the involvement of immunotherapy into the frontline setting.

A new standard of care has emerged in the treatment of patients with locally advanced, unresectable NSCLC based on data from the randomized, phase III PACIFIC trial, Everett E. Vokes, MD, told us when he stopped by. Initial data showed a 32% reduction in the risk of death with durvalumab compared with placebo in patients who had not progressed following concurrent chemoradiation, which led to the February 2018 approval of durvalumab. Three-year overall survival data showed a 31% reduction in the risk of death versus placebo. Despite this paradigm shift, questions remain with regard to sequencing strategies, Vokes said. In our interview, Vokes, the John E. Ultmann Professor of Medicine and Radiation Oncology, and physician-in-chief and chair of the Department of Medicine at University of Chicago Medicine, explained how the treatment of stage III NSCLC has evolved over the years and delved a little deeper into the unanswered questions prompted by PACIFIC.

After delivering an interesting presentation on pathologic considerations in NSCLC and the role of molecular testing, Jeremy Segal, MD, PhD, director of the Genomic and Molecular Pathologic Unit and associate professor of pathology in the Department of Pathology at the University of Chicago, joined us to discuss the topic further. He told us that the future of molecular testing in NSCLC lies in combined large-scale DNA and RNA analysis. He added that expanded sequencing can increase the detection of targetable mutations or molecular signatures and can also help to avoid misdiagnosis. In our interview, Segal provided insight into the evolving role of molecular testing in NSCLC, the different methods being utilized in practice, and future directions for testing.

Long-awaited overall survival data have established osimertinib as the standard frontline agent for patients with EGFR-mutant NSCLC, Mary J. Fidler MD, told us when she stopped by. However, she added that there’s room to improve upon osimertinib, whether that’s through the addition of angiogenic agents, or even chemotherapy. Updated data from the phase III FLAURA trial showed that treatment with osimertinib led to a median OS of 38.6 months versus 31.8 months with erlotinib or gefitinib in patients with EGFR-mutated NSCLC. At 3 years of follow-up, 54% of patients who received osimertinib arm were alive compared with 44% of those who received one of the second-generation TKIs, despite crossover between arms. In our interview, Filder highlighted the findings from the FLAURA trial and the clinical implications of those data, explained how osimertinib differs from other available TKIs, and delved into other emerging approaches that are making waves in the paradigm.

Next, we sat down with Nisha A. Mohindra, MD, an assistant professor of medicine in the Hematology/Oncology Division of Northwestern University’s Feinberg School of Medicine, to discuss promising agents that have emerged in ALK- and ROS1-positive NSCLC. Due to the development of selective TKIs, it’s no longer a question of whether these diseases can be targeted, but rather how to choose which agent is optimal out of the arsenal of available treatments, Mohindra told us. In our interview, Mohindra walked us through the current treatment approaches being used for patients with NSCLC who harbor these aberrations and highlighted some of the next-generation inhibitors that may possess the potential to shift sequencing approaches.

We closed out the evening with Lawrence E. Feldman, MD, who told us that after decades of minimal progress, recent regulatory updates with checkpoint inhibitors have generated excitement in extensive-stage small cell lung cancer treatment. For example, an update of the phase III IMpower133 trial presented at the 2019 ESMO Congress showed that the median overall survival remained at 12.3 months with the addition of atezolizumab to carboplatin plus etoposide compared with 10.3 months with carboplatin/etoposide alone at a median follow-up of 22.9 months. Furthermore, the phase III CASPIAN trial showed a similar OS improvement with durvalumab plus carboplatin/etoposide versus carboplatin/etoposide alone; specifically, median OS was 13.0 months compared with 10.3 months, respectively. In our interview, Feldman, a professor of clinical medicine at the University of Illinois Cancer Center, explained what the current treatment of SCLC looks like and the impact of immunotherapy on the space.

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