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Optimal Sequencing and Patient Selection Investigated in NSCLC

Danielle Bucco
Published: Monday, Dec 04, 2017

Frank E. Mott, MD
Frank E. Mott, MD
As novel agents, such as checkpoint inhibitors and targeted therapies, continue to emerge for the treatment of patients with non–small cell lung cancer (NSCLC), the sequencing of these agents is a new challenge for physicians.

This is particularly relevant for patients with EGFR mutations, as recent pivotal trial findings are likely to affect frontline therapy. For example, the phase III FLAURA study demonstrated an improved progression-free survival (PFS) when osimertinib (Tagrisso) was moved to the first-line setting for patients with EGFR-mutant NSCLC.

In the double-blind study, the median PFS was 10.2 months (95% CI, 9.6-11.1) for standard therapy, which was a first-generation EGFR inhibitor (erlotinib [Tarceva] or gefitinib [Iressa], and 18.9 months (95% CI, 15.2-21.4) with osimertinib (HR, 0.46; 95% CI, 0.37-0.57; P <.0001).

“This is traditionally used for patients with T790M acquired-resistant EGFR-positive disease. However, there are some data demonstrating that using it earlier in the first-line setting may have benefit,” explained Frank E. Mott, MD.

In an interview during the 2017 OncLive State of the Science SummitTM on Advanced Non–Small Cell Lung Cancer, Mott, an associate professor in the Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discussed optimal treatment selection strategies for patients with NSCLC.

OncLive: Can you discuss molecular profiling for patients with adenocarcinoma of the lung?

Mott: Adenocarcinoma of the lung has come a long way in the last decade in terms of new treatment options based on molecular targets. It is now standard of care to analyze the tumor for the presence of targets such as EGFR, ALK/ROS1, and PD-L1. There are some newer targets that have approved therapies; these include the MET exon 14 skipping mutation and BRAF mutations. 

What immunotherapy and targeted therapies are showing excitement right now?

In ALK-positive tumors, which only represent 2% to 4% of patients with NSCLC, we have new data suggesting that targeted therapies demonstrate a better response than chemotherapy. Also, some newer agents, such as alectinib (Alecensa), are demonstrating good penetration for patients with central nervous system metastases. Those patients are responding well with good durable responses in PFS. We are seeing changing patterns of care with some of these drugs.

The immunotherapy area is also very exciting. There are many ongoing studies, but we have had at lease 3 immunotherapy drugs to prove the benefit for patients with advanced adenocarcinoma or squamous cell carcinoma of the lung. This has been an exciting era and there is a lot of work still ongoing. 

What ongoing trials are showing promise in the pipeline?

I highlighted a study that we are doing at The University of Texas MD Anderson Cancer Center investigating EGFR mutations with the exon 20 insertion mutations. This is a rare mutation seen in about 1% to 2% of patients. Up until now, these patients did not have a good response to the standard first-line tyrosine kinase inhibitors (TKIs). We are looking at a drug called poziotinib; early data have shown a response rate of 74% to 75% in a disease that previously did not have good [available] treatment. Hopefully, this is something exciting.

We have the data for immunotherapy used in the first- and second-line settings in advanced disease. We are now starting to look at these agents earlier on, even in the neoadjuvant setting. There are several trials investigating this, as well. We think that is the next era of use for these agents. 

How do you determine the sequencing of these agents and when to give 1 regimen over another?

That is a difficult decision. There are many factors that go into that, such as the histology and the profile of the tumor—as well as the patient, their comorbidities, and so forth. For example, immunotherapy indications are based on PD-L1 levels, which influences the choice of giving PD-1/PD-L1 inhibitors early on. 

[For patients with driver mutations], the decision of which TKI to use first is somewhat similar. The ALEX study suggests using alectinib for patients with ALK-positive tumors as it has supplanted crizotinib (Xalkori) as the first-line therapy.

There was another study presented at the 2017 ESMO Congress, which looked at osimertinib in the first-line setting. There is a movement focused on moving osimertinib further up the ladder. 


View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: Working Group to Optimize Outcomes in EGFR-mutated Lung Cancers: Evolving Concepts for Nurses to Facilitate and Improve Patient CareJun 30, 20181.5
Community Practice Connections™: 4th Annual Miami Lung Cancer Conference®Jun 30, 20187.0
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