Jamie E. Chaft, MD
The oncology community is eagerly awaiting the pivotal data from the phase III FLAURA trial, which will determine the benefit of osimertinib (Tagrisso) in the frontline setting for patients with EGFR
-mutated non–small cell lung cancer (NSCLC) who harbor the acquired resistance mutation T790M
Earlier findings from the phase I AURA trial, which investigated the agent in the first-line setting in 60 patients across 2 different dose cohorts, demonstrated a 77% objective response rate (95% CI, 0.64-0.87).1
Moreover, the median progression-free survival (PFS) was 19.3 months; 55% of patients remained progression-free at 18 months, and the median duration of response was non-calculable at the time of data cutoff.
The phase III findings would also follow the updated results of the phase III AURA3 trial, which showed that treatment with osimertinib reduced the risk of disease progression by 70% versus a chemotherapy doublet regimen for patients with EGFR
T790M-mutant NSCLC who progressed after first-line targeted therapy.2
The AURA3 results led to the recent conversion of the accelerated approval of osimertinib in this setting to a full approval.
Jamie E. Chaft, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, shared insight on the available EGFR TKIs in lung cancer during the 2017 OncLive®
State of the Science Summit on Advanced Non–Small Cell Lung Cancer. In an interview, she spoke to the effectiveness of osimertinib and what the future holds for patients with EGFR
OncLive: You lectured on EGFR TKIs at this meeting. How has this space evolved?
We currently have 4 EGFR TKIs that are FDA-approved for the treatment of NSCLC in the United States. There are 2 first-generation drugs, 1 second-generation drug, and a third-generation drug, osimertinib, which is the newest addition. The second-generation drugs are for newly diagnosed cancers, and osimertinib is indicated to be administered at the time of progression in patients whose tumors have a T790M
What are some of the most recent advances with TKIs in NSCLC?
The most recent advance is still osimertinib’s approval. It was approved in November 2015 for EGFR
-mutant lung cancer with a T790M
mutation. More recently, there was the publication of the AURA3 data, which really confirm osimertinib’s drastic superiority over chemotherapy in this setting.
An additional major advance has been the investment of the industry to have the ability to detect EGFR
mutations in the blood. This is both faster and safer than a re-biopsy, small biopsies, or insufficient tissue for tumor tissue analysis in many of our patients who are diagnosed with NSCLC.
It really does open up a line of therapy to a percentage of patients who would not have otherwise had it.
What are the current challenges we face with sequencing therapies, if any?
Today, there is not much of a challenge. The treatment algorithm is fairly obvious, in terms of approvals. The third-generation drug will follow either a first- or second-line agent.
At this meeting, we talked about the controversy over the superiority of first- versus second-generation drugs. My interpretation of the data is that the second-generation drug afatinib (Gilotrif) has more toxicity and does not have an obvious therapeutic advantage over the first-generation drugs.