Dr. Melissa Johnson, Associate Director of Lung Cancer Research at Sarah Cannon Research Institute, shares exciting developments in the research and treatment of non-small cell lung cancer (NSCLC).
Advances in immunotherapy
There have been exciting developments recently in immunotherapy research for NSCLC. Specifically, there were many important front-line immunotherapy trials reported at the American Society of Clinical Oncology (ASCO®) Annual Meeting in June 2018.
One of the most eagerly awaited trials was the KEYNOTE-042 clinical trial, which demonstrated improved survival for NSCLC patients who are treated with immunotherapy rather than chemotherapy. Another practice-changing research trial presented was KEYNOTE-407, which showed that combining immunotherapy with chemotherapy also prolonged survival in patients with squamous lung cancer. As a result, the National Comprehensive Cancer Network (NCCN) voted to expand their recommendation for front-line immunotherapy to the squamous patient population. Additionally, the KEYNOTE-189 clinical trial, published at the American Association for Cancer Research Annual Meeting in April 2018, showed similar benefit of chemotherapy and immunotherapy for patients with non-squamous lung cancer.
Previously, immunotherapy was used specifically for the treatments of patients with refractory lung cancer. These research advancements have resulted in a paradigm shift where patients who may have only received immunotherapy after other treatment options are now receiving it as front-line treatment. This means that any patients with front-line lung cancer can at least expect to discuss immunotherapy or immunotherapy in combination with chemotherapy with their oncologist.
While KEYNOTE-042 enrolled NSCLC patients whose tumors expressed a protein called Programmed Death Receptor Ligand-1 (PD-L1) at levels of at least 1%, a third first-line trial presented at ASCO® called CheckMate 227, showed that patients whose tumors with low PD-L1 scores (PD-L1 <1%) do well by combining two immunotherapy agents - nivolumab and ipilimumab.
Advances in next generation sequencing (NGS)
Still other NSCLC patients have better survival when treated with oral targeted therapies rather than chemotherapy or immunotherapy (typically given by intravenous infusion). Oral therapies such as LOXO-292 and larotrectinib have emphasized the importance of early molecular profiling for all cancer patients to identify patients whose tumors harbor driver-oncogenes that can be treated with targeted therapies. Many targeted therapies are available in clinical trials being conducted at Sarah Cannon clinics.
Also presented at this year’s ASCO® was an abstract showing next-generation sequencing (NGS) for NSCLC patients was more cost effective than sequential mutation testing, resulting in $1.4-$2.1 million dollars in cost savings for the Center for Medicare and Medicaid Services (CMS).
NGS is an approach that allows simultaneous, parallel testing of DNA for hundreds of genes associated with cancer development from a single piece of tumor tissue. By choosing to order NGS testing rather than tests for individual mutations, one test at a time, doctors can gain much more information using far less tissue, time and expense.
One additional piece of information that an NGS profile approach offers is the tumor mutation burden, a quantification of the neo-antigen burden, which are mutations that exists in a particular tumor. The higher the tumor mutation burden, the more the patient is likely to respond to immunotherapy. This is an emerging biomarker that is part of a molecular profiling report that helps explain how well a patient will respond to immunotherapy.
Finally, data at ASCO® showed that patients who have oncogene drivers in their cancer, like EGFR and ALK1, do not have the same benefit from immunotherapy early in their treatment, but can be treated with targeted therapies. NCCN recommends upfront molecular profiling for EGFR, ALK1 and BRAF at the same time, which provides more information initially and a better first shot of treatment of effective therapies.
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