How Genomic Profiling is Shifting the Treatment Paradigm for Rare Lung Cancers

Christine Ward, Oncology Precision & Translational Medicine, Takeda Oncology, Geoff Oxnard, Clinical Development, Foundation Medicine Inc.

As the discovery and treatment of cancer continues to evolve, comprehensive genomic profiling (CGP), using next-generation sequencing (NGS) technology, has emerged as a necessary and accessible tool for improving diagnosis. Coupled with advancements in lung cancer treatment, CGP has redefined how clinicians approach diagnosis and the guidance they are able to provide their patients.

To hear about the role of CGP in Oncology, Christine Ward, PhD, Head of Oncology Precision & Translational Medicine at Takeda Oncology, spoke with Geoff Oxnard, MD, Vice President and Head of Clinical Development at Foundation Medicine Inc. A leading company in molecular insights, Foundation Medicine is dedicated to transforming cancer care by providing oncologists with a deep understanding of the genomic changes that contribute to each patient's unique cancer to help inform treatment.

Christine Ward: Can you speak to the importance of CGP in Oncology?

Dr. Geoff Oxnard: We are living in a time where clinicians and patients can benefit from incredible therapeutic advances, whether that be targeted therapies, immunotherapy or clinical trials. While it is exciting to have so many new options, determining which treatment is best for each patient is becoming increasingly complex and often times, overwhelming. As such, it is critical that oncologists have tools to understand what is driving a patient’s cancer and which treatment option(s) will provide the most benefit; this is where CGP comes in. CGP provides physicians with more complete information about what is driving a patient’s cancer at the molecular level, so they can make more informed treatment decisions for their patients.

Dr. Ward: Can you explain the role CGP plays in the diagnosis of people with rare forms of cancer, such as epidermal growth factor receptor (EGFR) Exon20 insertion+ metastatic non-small cell lung cancer (mNSCLC)? How should physicians be approaching testing today?

Dr. Oxnard: There has been a fundamental shift in the treatment of cancer. Where we once took a “one-size-fits-all” approach to treatment, we are now able to individualize based on each patient’s biology. Over the past decade, lung cancer specifically has emerged as the poster child of precision oncology.  And, with advances in treatment, we’ve seen an important need for broader molecular testing to help physicians determine which treatment(s) will benefit their patient and conversely, which treatments will not.

The question today is, “What molecular testing is good enough for advanced lung cancer?” We have moved beyond the time where testing for single or a small group of biomarkers like EGFR, ALK or ROS using targeted gene panels that provide only “hotspot” coverage was the only option for informing patient care. These more limited testing approaches can miss rare mutations that may make patients eligible for certain targeted treatment options, including clinical trials. Today, there are therapies being investigated to treat rare subtypes of NSCLC, such as EGFR Exon20 or HER2, but patients may not be tested for them regularly.

Through the use of broad NGS testing, physicians are able to uncover more potential treatment options that stretch beyond those approved for a handful of more common biomarkers.

Dr. Ward: What limitations still exist in the diagnosis of rare forms of lung cancer, and how can physicians address them?

Dr. Oxnard: Historically, proper testing required a good biopsy specimen to be collected to enable NGS testing and provide an actionable result for physicians. We recognize that there is a significant portion of patients where tumor genotyping is not feasible because of limited tissue available or difficult-to-biopsy tumors – so what are the options for these patients? Previously, a physician would have to collect more tissue, which is still standard in many lung cancer practices. But today, we have more diagnostic options. Liquid biopsy NGS testing, which evaluates circulating tumor DNA in the patient’s bloodstream, is a compelling solution for many patients.

Dr. Ward: Despite these advanced testing tools, there is still a large percentage of patients who are not being tested for these rarer forms of cancer. Why do you think that is?

Dr. Oxnard: I often ask fellow clinicians if they have ever treated a case of mesothelioma, a cancer primarily caused by exposure to asbestos, and the majority will say yes. But if you ask them if they have ever treated a rare form of cancer like EGFR Exon20 insertion+ mNSCLC, only a few may be familiar with it. Interestingly, their relative prevalence is about the same. The reason physicians haven’t seen the latter as often is likely because they haven’t looked for it.

In order to help more patients benefit from precision cancer care, we need to ensure CGP is the standard of care for all advanced cancer patients. These rare genotypes are under our noses, but we need to test for them to find them and treat them.

Dr. Ward: How can we make CGP a standard practice, and what would this mean for patients diagnosed with cancer?

Dr. Oxnard: First, we need to educate clinicians on the diagnostic tools available to them and encourage them to use a combination of tissue and liquid NGS testing approaches as is clinically appropriate. If we can educate on the diagnostic paradigm, then we can ensure patients are receiving the right testing and therefore, an informed treatment plan. Secondly, we need to capture the spirit of optimism that emerges from proper testing and diagnosis, creating opportunities for clinicians and patients alike. Lastly, patients can be a powerful voice in their care. We need to tap into advocacy groups to educate patients and encourage them to speak up and demand CGP from their providers.

Dr. Ward: Why are partnerships, such as those with Takeda and Foundation Medicine, so important to help support and advance diagnosis of patients?

Dr. Oxnard: For patients to access the treatment options best suited for them, you need a combination of treatment availability and diagnostic availability. This requires a close and effective partnership between a drug developer, like Takeda, and a diagnostic company, like Foundation Medicine, to co-develop a drug and a diagnostic. We are constantly working to solidify this synergy with our partners, so we can work in parallel to maximize success throughout the development of the therapy and the matching assay, ultimately improving care for cancer patients globally.