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Developments Expanding Frontline NSCLC Treatment

Danielle Bucco
Published: Friday, Apr 13, 2018

Thomas Eldridge Stinchcombe, MD
Thomas Eldridge Stinchcombe, MD
Osimertinib (Tagrisso) and alectinib (Alecensa) are 2 new frontline therapies for patients with non–small cell lung cancer (NSCLC) that have demonstrated tremendous advancements for targeted therapy, said Thomas E. Stinchcombe, MD.

In the phase III FLAURA study, osimertinib reduced the risk of progression or death by 54% versus standard tyrosine kinase inhibitor (TKI) therapy of erlotinib (Tarceva) or gefitinib (Iressa) in patients with EGFR-mutant NSCLC. In this trial, 556 treatment-naïve patients with EGFR-positive, locally advanced or metastatic NSCLC were randomly assigned to osimertinib or standard TKI therapy. The median progression-free survival (PFS) was 10.2 months (95% CI, 9.6-11.1) for standard therapy and 18.9 months (95% CI, 12.5-21.4) with osimertinib (HR, 0.46; 95% CI, 0.37-0.57; P <.0001). Osimertinib is currently under priority review as a frontline treatment option for this patient population.1 The objective response rate (ORR) with osimertinib was 80% compared with 76% for erlotinib and gefitinib (OR, 1.28; 95% CI, 0.85- 1.93; P = .2335). The median duration of response with osimertinib was 17.2 months versus 8.5 months in the comparator arm.

Representinng another targeted therapy win, the FDA approved alectinib in November 2017 for the treatment of patients with ALK-positive metastatic NSCLC. The frontline approval of alectinib is based on the phase III ALEX study, findings of which demonstrated a 47% improvement in PFS (HR, 0.53; 95% CI, 0.38- 0.73; P <.0001) compared with crizotinib (Xalkori).2

In this international trial, the median PFS, as determined by an independent review committee, was 25.7 months (95% CI, 19.9-not reached) in the alectinib arm versus 10.4 months (95% CI, 7.7-14.6) in the crizotinib arm. The ORR with alectinib was 79% (95% CI, 72%-85%) versus 72% (95% CI, 64%-79%) with crizotinib (= .1652). The complete response rates were 13% and 6%, respectively, and the partial response rate was 66% in both arms.

In an interview during the 2018 OncLive® State of the Science Summit™ on Non–Small Cell Lung Cancer, Stinchcombe, a professor in the Division of Medical Oncology at Duke University and member of Duke Cancer Institute, discussed existing and emerging first-line regimens coming through the pipeline for the treatment of patients with NSCLC.

OncLive®: What are your thoughts on osimertinib and alectinib as first-line treatments for patients with NSCLC?

Stinchcombe: There have been tremendous advances with targeted therapy in the last year. A phase III trial compared osimertinib with erlotinib and gefitinib. This revealed an improved PFS with a median of 18.9 months [with osimertinib], which also demonstrated lower grade 3/4 toxicities.

This is a trial that has immediately changed practice.  For patients with ALK-rearranged NSCLC, there are 2 trials. Both trials compared alectinib with the previous standard of crizotinib and demonstrated a significant improvement in PFS, with the median being 25 months in the alectinib arm.


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Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: Oncology Best Practice™: Choosing Therapies for Patients with EGFR-mutant Lung Cancers: More Options... More Decisions... Better OutcomesApr 27, 20182.0
Community Practice Connections™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations Across Lung, Head and Neck, and Bladder CancersApr 28, 20182.0
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