Spotlighting New Standards in Lung Cancer in Salt Lake City

We recently traveled to Salt Lake City, Utah for a State of the Science Summit™ on Non­—Small Cell Lung Cancer. At the meeting, faculty from the University of Utah and Intermountain Healthcare, delved into biomarker discoveries, research regarding the heredity of lung cancer, emerging treatment modalities, and practice-changing trials that have impacted the paradigm. Other topics included the role of immunotherapy and exciting combinations that are generating excitement in this space as well as novel drugs that are revolutionizing the treatment of patients with non–small cell lung cancer (NSCLC) whose tumors harbor ROS1 or ALK mutations.

First, we spoke with the chair of the meeting, Wallace L. Akerley, MD, a professor of internal medicine and director the Lung Cancer Disease Center of Excellence at Huntsman Cancer Institute of the University of Utah. Akerley told us that patients should undergo broad molecular profiling in order to determine whether they stand to benefit from the increasing array of targeted therapies that are showing remarkable responses. The emergence of these biomarkers has completely changed the way patients with lung cancer are treated, said Akerley. In our interview, Akerley shed light on targeted approaches available for patients with NSCLC who harbor MET, RET, or HER2 alterations.

Afterward, William T. Sause, MD, stopped by to explain how the treatment for patients with stage III NSCLC has evolved over the past few decades to include modalities such as chemoradiation and immunotherapy. According to Sause, one of the biggest improvements that have been made is in patient selection. Another key area of advancement has been the introduction of immunotherapy into the paradigm, he added. In our interview, Sause provided a historical perspective on the optimal management of patients with stage III NSCLC.

Next, Trudy G. Oliver, BSc, PhD, stopped by to discuss her research with mouse models in lung cancer. When she sat down with us, she expanded on the rationale for using mouse models in lung cancer, some of the work being done with these models, how this work is contributing to a better understanding of lung cancer subtypes, and the novel targets that have been identified via this research.

After delivering an intriguing presentation on the heredity of lung cancer, Lisa A. Cannon-Albright, PhD, an adjunct professor of Family and Preventative Medicine and a professor of Internal Medicine at the University of Utah School of Medicine, joined us to discuss the topic further. She told us that by tracing Utah’s genealogy back to its founders, her team has been able to identify the subset of family pedigrees with the greatest predisposition to lung cancer, thus arming investigators with the potential to uncover genetic components of the disease and inform prophylactic measures. According to Cannon-Albright, who is also chief of Genetic Epidemiology at the University of Utah, family history is key to understanding heredity in lung cancer. Specifically, the presence of a positive family history for lung cancer is indicative of increased risk for the disease. In our interview, Cannon-Albright shared some of her research and shed light on histologic subgroups at increased risk of lung cancer.

Overall survival data from the phase III FLAURA trial presented at the 2019 ESMO Congress have solidified osimertinib as the new frontline standard for patients with EGFR-mutated NSCLC, Clarke A. Low, MD, told us when he stopped by. The third-generation TKI was found to improve median OS by 6.8 months when compared with the second-generation TKIs erlotinib or gefitinib in this patient population, despite crossover between arms. Specifically, Low told us that the median OS was 38.6 months versus 31.8 months in the osimertinib and comparator arms, respectively, which translated to a 20% reduction in the risk of death. In our interview, Low, director of thoracic oncology at Intermountain Healthcare, provided insight on the role of osimertinib in EGFR-mutated disease and shared next steps for research in this space.

Another practice-changing trial was the phase III PACIFIC trial, in which the PD-L1 inhibitor durvalumab improved survival in patients with stage III NSCLC, said Anna Chalmers, MD. Findings from the initial analysis of the trial showed a 32% reduction in the risk of death versus placebo, which led to the FDA approval of the immunotherapy drug for use in this patient population. Three-year follow-up data from a posthoc overall survival analysis continued to show a benefit with the agent. These data changed the standard of care for this patient population and opened the door for potential concurrent chemoradiation and immunotherapy combinations. In our interview, Chalmers, a clinical instructor in the Division of Oncology and an investigator at Huntsman Cancer Institute of the University of Utah, discussed the implications of the PACIFIC trial on the treatment of those with stage III disease.

Sonam Puri, MD, an assistant professor in medical oncology at Huntsman Cancer Institute of the University of Utah, then stopped by to elaborate on the various novel immunotherapy combinations that have emerged in the treatment of patients with metastatic nonsquamous NSCLC, a field that has seen quite a lot of growth over the past couple of years. Combinations of immunotherapy with HDAC or VEGF inhibitors are of particular interest and are the focus of several ongoing trials in the pipeline, according to Puri. In our interview, Puri discussed key developments in metastatic nonsquamous disease, the impact of immunotherapy, and some of the pivotal trials that have impacted treatment decisions.

In the stage IV squamous NSCLC setting, immunotherapy has emerged as the preferred frontline treatment, according to Shiven B. Patel, MD, MBA, FACP. However, the question of which subsets benefit most from using it in combination with chemotherapy is still unanswered. To improve on the benefit seen with pembrolizumab monotherapy, the agent was then examined in combination with chemotherapy in the KEYNOTE-407 trial. After a median follow-up of 7.8 months, the median OS was 15.9 months with chemoimmunotherapy versus 11.3 months in the placebo arm. These data led to the October 2018 approval of the PD-1 inhibitor in combination with carboplatin and either paclitaxel of nab-paclitaxel for the treatment of patients with metastatic squamous disease. Also, the addition of atezolizumab to carboplatin and nab-paclitaxel led to a clinical OS benefit among a subset of patients with advanced squamous disease, according to data from the phase III IMpower131 trial. In our interview, Patel delved deeper into pivotal trials examining chemoimmunotherapy in NSCLC and provided insight into how to apply these data to practice.

We closed out the evening with Katie Kerrigan, MD, who told us that following the 2016 FDA approval of crizotinib agents designed to target ROS1-mutated advanced NSCLC have been rapidly emerging and showing impressive signals of activity. One such agent was entrectinib, which demonstrated a 79.2% objective response rate in this patient subgroup. According to Kerrigan, a hematology/oncology fellow at the University of Utah School of Medicine, the approval of crizotinib revolutionized the treatment of this disease. The ALK-positive NSCLC space has also experienced growth with agents in the first-line setting like alectinib and ceritinib and lorlatinib and brigatinib in the second-line space. In our interview, Kerrigan provided insight into the novel agents that have emerged in the treatment of patients with ROS1- and ALK-mutated NSCLC and the sequencing challenges that remain.

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