Advances in Treating Non-Small Cell Lung Cancer

In a session in the Oncology track, James R. Jett, MD, chief medical officer for Oncimmune LLC and coeditor of the Lung Cancer section of Up-to-Date, provided attendees with presentation titled Informed Decision Making in Advanced Non-Small Cell Lung Cancer.

He began with current clinical advances in cancer treatment. He said that 1.7 million people in the United States received a diagnosis of cancer in 2016; two out of three people with cancer live at least 5 years following the diagnosis. Between November 2015 and October 2016, the US FDA approved 20 therapies for 12 different types of cancer and in 2016 alone, the FDA approved immune therapies for advanced lung cancer, kidney cancer, bladder cancer, head and neck cancers, and Hodgkin lymphoma. Over the past 5 years, 15 indications for immune therapies have been granted approval from the FDA.

Changes in treatment for stage IV non-small cell lung cancer (NSCLC) include sensitizing somatic mutations in adenocarcinoma: epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS-1; EGFR (T790M) inhibitors (osimertinib is now considered frontline treatment), new frontline ALK inhibitors include alectinib and ceritinib. Recent changes include use of precision medicine, EGFR liquid biopsy, ALK translocations, and immune check point inhibitors, all leading to improved long-term survival. “Precision cancer medicine refers to treatment planning based on detection of driver mutations,” Dr. Jett said.

Another promising advancement is next-generation sequencing (NGS). In a recent study, 101 patients with advanced NSCLC underwent NGS testing following negative or inconclusive EGFR/ALK testing. NGS identified clinically actionable genomic alterations in 50% of the patients (EGFR, 18%; RET, 9%; ALK, 8%; MET, 6%; and ERBB-2, 5%). Fifteen patients had EGFR/ALK mutation after prior negative testing. Treatment strategy was changed in 43 patients. NGS uses less tissue than profiling with multiple non-NGS tests and identifies actionable genomic alterations that may be missed with non-NGS tests.

The session concluded with an overview of long-term survival for patients with stage IV NSCLC.  A retrospective review published in 2017 [Magnuson WJ et al. J Clin Oncol], included 351 patients from six centers with EGFR-sensitive brain metastases and no prior treatment with tyrosine kinase inhibitors (TKIs). Patients with stereotactic radiosurgery followed by treatment with TKIs had median survival of 46 months, compared with 30 months for patients who underwent whole brain radiation therapy or 25 months for patients who were treated with TKI alone.

In summary, Dr. Jett stressed the advances in the treatment of stage IV NSCLC over the past 5 years. “Osimertinib is likely to move to frontline treatment for EGFRm NSCLC, alectinib will move to frontline treatment of ALK-mutated NSCLC, and durvalumab is likely to be FDA approved for stage III NSCLC following chemotherapy and radiation therapy. Immunotherapy is likely to move to frontline therapy in selected NSCLC,” he said.

“Five-year survival with stage IV NCLSL is now being observed in selected cases,” he added.

James Jett, MD. Informed Decision-Making in Advanced Non-Small Cell Lung Cancer (NSCLC): Expert Strategies for Individualized Treatment. 2017 Fall Managed Care Forum. October 27, 2017.