Lecia V. Sequist, MD, associate professor of medicine, Harvard Medical School, Mary B. Saltonstall Chair, Oncology, Massachusetts General Hospital Center, discusses combination regimens for patients with 

-positive non—small cell lung cancer (NCSLC).

Sequist says that one of the unique benefits of the third-generation agents having fewer adverse events is that there are more possibilities for combination regimens. In the past, frequently used agents such as erlotinib (Tarceva) or afatinib (Gilotrif) in combination with other therapies caused high rates of toxicities.

Moving forward, Sequist says that she is looking out for new trials with third-generation agents. There is potential in combinations of 2 EGFR-targeting drugs, or combinations with MET, JAK, or BRAF inhibitors. These combination trials will be done in the resistance setting or possibly the frontline setting, Sequist adds.  

Videos

Lecia V. Sequist, MD, associate professor of medicine, Harvard Medical School, Mary B. Saltonstall Chair, Oncology, Massachusetts General Hospital Center, discusses combination regimens for patients with EGFR-positive non-small cell lung cancer (NCSLC).
 

Dr. Sequist Discusses Combination Regimens in EGFR+ NSCLC

Lecia V. Sequist, MD, associate professor of medicine, Harvard Medical School, Mary B. Saltonstall Chair, Oncology, Massachusetts General Hospital Center, discusses the tolerability of a new third-generation T790-specific inhibitor, osimertinib (Tagrisso).

Promising data from the FLAURA study, presented at the 2017 ESMO Congress, detailed a randomized trial looking at a new third-generation T790-specific inhibitor called osimertinib. Though this drug is typically given in the second-line setting after acquired resistance, the trial tested its efficacy in the frontline setting. It was also compared with standard regimens of erlotinib (Tarceva) or gefitinib (Iressa). Results showed the drug had almost double the median progression-free survival (PFS), suggesting a much more tolerable safety profile.

The difference between osimertinib and other third-generation drugs not yet approved is in their 

 wild-type activity level. Third-generation drugs have very little activity against 

 wild-type, whereas first- and second-generation drugs have some degree of inhibition of 

 wild-type. The inhibition of that wild-type is responsible for rashes and diarrhea in patients. Osimertinib has much less rash and diarrhea and greater tolerability in patients, Sequist confirms.

Dr. Sequist Distinguishes Osimertinib From Earlier NSCLC TKIs

Lecia V. Sequist, MD, medical oncologist, associate professor, Massachusetts General Hospital, Harvard Medical School, discusses the overall survival analysis of the LUX-Lung 3 and LUX-Lung 6 trials.

Over the past several years, 7 trials have examined erlotinib and gefitinib compared with chemotherapy for the treatment of lung cancer patients with 

 mutations. These studies have all shown progression-free survival (PFS) and objective response benefit with the EGFR inhibitors.

Sequist says the PFS data from LUX-Lung 3 and LUX-Lung 6 led to the approval of afatinib in many countries. Identical results were seen between the two studies — there was no survival advantage between afatinib and chemotherapy, though patients with different 

 mutations experienced varying degrees of benefit.

View more from the 2014 Multidisciplinary Symposium in Thoracic Oncology

Dr. Sequist Discusses the OS Analysis of LUX-Lung 3 and LUX-Lung 6

Lecia V. Sequist, MD, medical oncologist, associate professor, Massachusetts General Hospital, Harvard Medical School, discusses the efficacy of CO-1686 for the treatment of non-small cell lung cancer (NSCLC).

 mutations define a group of patients that respond well to EGFR TKIs. These patients, though, often face resistance due to an acquired T790M mutation that occurs after about a year of treatment. This has been a vexing problem, Sequist says.

Now, researchers and oncologists are seeing activity in this setting with several agents. In an ongoing phase I trial presented at the 2014 ASCO Annual Meeting, it was reported that a number of patients responded to CO-1686. In this study, 58% of patients experienced an overall response across all dose levels.

Lecia V. Sequist, MD, medical oncologist, associate professor, Massachusetts General Hospital, Harvard Medical School, discusses the efficacy of CO-1686 for the treatment of non-small cell lung cancer.

Dr. Sequist Discusses the Efficacy of CO-1686 for NSCLC

Lecia V. Sequist, MD, medical oncologist, associate professor, Massachusetts General Hospital, Harvard Medical School, discusses adverse events (AEs) associated with CO-1686 for patients with non-small cell lung cancer (NSCLC).

CO-1686 was well tolerated in a phase I study presented at the 2014 ASCO Annual Meeting – AEs associated with CO-1686 were infrequent and mild. Nausea and hyperglycemia were most commonly observed, Sequist says, two AEs that are not commonly seen with other EGFR-inhibiting drugs.

Sequist says the question remains as to why these AEs are occurring. Physicians can adequately monitor patients that experience these AEs and stay away from severe episodes by reducing the dose of the study medicine and adding blood sugar-lowering medicine such as metformin.

Lecia V. Sequist, MD, medical oncologist, associate professor, Massachusetts General Hospital, Harvard Medical School, discusses adverse events (AEs) associated with CO-1686 for patients with non-small cell lung cancer.

Lecia V. Sequist, MD

Articles

Dr. Sequist Discusses Combination Regimens in EGFR+ NSCLC

Dr. Sequist Distinguishes Osimertinib From Earlier NSCLC TKIs

Dr. Sequist Discusses the OS Analysis of LUX-Lung 3 and LUX-Lung 6

Dr. Sequist Discusses the Efficacy of CO-1686 for NSCLC

Dr. Sequist Discusses Adverse Events Associated With CO-1686