Expanding Options for Individualized Treatment of Advanced NSCLC

James R. Jett, MD, gave an overview of the advances in diagnosis and treatment of non—small cell lung cancer (NSCLC) during a session at the National Association of Managed Care Physicians Fall Managed Care Forum 2017.

Jett, who is chief medical officer of Oncimmune, LLC, explained that when he began his oncology career in 1980, patients with advanced NSCLC were offered supportive care and were expected to live just 4 to 5 months. In the decades since, the discovery of new tumor mutations and treatment options such as immune checkpoint inhibitors have extended the median survival to 30 months, as two-thirds of patients diagnosed with NSCLC now will be alive at 5 years.

“What you learned about cancer 5 years ago is way out of date,” Jett warned the audience.

His presentation focused on 6 recent areas of development that have changed the diagnosis and treatment landscape for this cancer. The first, precision medicine, has led oncologists to plan treatment based on detection of sensitizing mutations, ending the era when all cancers were treated the same. In a study of next-generation sequencing (NGS) in 101 patients with NSCLC, 50% had an actionable mutation, and treatment strategies changed for 43 patients.

“If I get a cancer, you can bet I want next-gen sequencing,” Jett said.

He also highlighted the benefits of testing for epidermal growth factor receptor (EGFR)—sensitizing mutations, which can help identify patients who are more likely to respond to drugs such as osimertinib. As second-line therapy in patients with EGFR-mutated NSCLC, it produced better progression-free survival (PFS) than platinum­–pemetrexed and was also better tolerated. Based on the results of a recent trial, Jett predicted that it would be approved by the FDA as a frontline therapy within the next year or sooner.

The next exciting development he mentioned was the use of liquid biopsies to examine tumor circulating DNA through a simple blood draw. This is an especially appealing option for patients with NSCLC who may experience a pneumothorax from having a biopsy needle in their chest. The sensitivity of these tests to genetic and epigenetic changes has improved dramatically in recent years, yet another example of how “technology is rapidly changing and the field is changing,” Jett said.

Next in the discussion was anaplastic lymphoma kinase (ALK) translocations, which make patients better candidates for drugs like crizotinib instead of chemotherapy. Jett showed a slide of a patient’s tumor before, and 2 weeks after, crizotinib therapy, with the tumor noticeably smaller in the second scan, indicating what he called a “gee whiz improvement.”

Another promising option for patients with ALK translocations has been the research into alectinib, which demonstrated longer PFS and fewer patients experiencing disease progression or death compared with crizotinib in a recent trial. Jett predicted that it would be approved by the FDA very quickly, although many clinicians are using it as frontline therapy already.

He called the results “really dramatic, if you’re as old as I am and saw how poorly they did in the ‘80s with chemotherapy.”

Immune checkpoint inhibitors represent another treatment option with potentially dramatic benefits. There are 3 currently approved for NSCLC, and Jett anticipated that durvalumab would soon be approved as maintenance therapy. He highlighted several studies showing the performance of checkpoint inhibitors like pembrolizumab, and mentioned that the FDA’s site-agnostic approval of pembrolizumab in the presence of certain biomarkers was a “game changer in the treatment of cancer.”

While immunotherapies can result in some toxicities not seen with chemotherapy, Jett explained that the American Society of Clinical Oncology and the National Comprehensive Cancer Network will release guidelines later this year on how to manage these toxicities. Regardless, the research surrounding immuno-oncology makes for “exciting times,” he said, especially with the knowledge that tumor mutational burden and PD-L1 staining are the strongest predictors of response.

The prognosis for patients with brain metastases from NSCLC has improved as well, due to research on drugs like alectinib, which has demonstrated better central nervous system (CNS) penetration in patients with ALK-positive NSCLC, resulting in higher response rates, longer duration of response, and lower rates of CNS progression compared with crizotinib.

Finally, Jett discussed the odds of long-term survival with advanced NSCLC, which are growing more positive with the discovery of new treatment regimen options and the adoption of NGS as the standard of care worldwide.

“Five-year survival was unheard of early in my career,” Jett said, “but maybe that discussion can change.”