AstraZeneca’s Tagrisso Keeps Most Lung Cancer Patients With Mutation Alive Two Years After Surgery

Tagrisso, the targeted therapy made by AstraZeneca, could become the treatment of choice for the majority of lung cancer patients with mutations in a certain gene who are treated after surgery, based on results presented this weekend at the American Society of Clinical Oncology (ASCO) annual meeting.

Tagrisso (osimertinib), a third-generation EGFR tyrosine kinase inhibitor, is already the first choice to treat patients with EGFR-mutated, non-small cell lung cancer (NSCLC) at an advanced stage. Results from the ADAURA trial (NCT02511106) presented at the oncologists’ meeting suggest it could become the first choice for NSCLC patients whose cancer was diagnosed at an earlier stage. The trial was unblinded in April after a review board saw a clear benefit.

According to a 2015 article in Translational Lung Cancer Research, rates of EGFR overexpression vary by subtype of NSCLC; they can fall between 40% and 89%, with the highest rates seen in squamous tumors. Rates are highest among patients with NSCLC who have never smoked.

Related: Anna Lee Shares ASCO Study on Changes in Cancer Mortality Rates (VIDEO)

Lead study author Roy S. Herbst, M.D., Ph.D., of the Yale Cancer Center, called the results from the phase 3 trial a “home run” and said the results clearly point to treating early-stage lung cancer patients whose cancers have the EGFR mutations Tagrisso.  He noted that half the patients with stage IB NSCLC who have been treated with surgery see their cancer return and that recurrence rates climb for those diagnosed at later stages.

But in the ADADURA trial,  90% of the patients with cancers more at a more advanced stage-either stage II or stage IIIA-who were treated Tagrisso were alive two years after surgery and without  cancer recurrence compared with 44% of those who received placebo, according to results that were released late last week and presented by Herbst during Sunday’s plenary session, a high-profile event at the meeting reserved for finding that organizers believe are most important. The ASCO meeting is usually held in Chicago but this year it moved to an online format because of COVID-19

Herbst and his colleague also reported that the stage II or stage IIIA  patients treated with Tagrisso were 83% less like likely to have died or had their cancer recur than the patients in the placebo group.   

“Collectively, these data support the use of osimertinib as an appropriate treatment in the long-term adjuvant setting,” Herbst said during the plenary session.  The drug’s safety and tolerability are key factors, given an anticipated 3-year treatment course. Going forward, Herbst said researchers would examine whether patients taking the therapy see cancer return elsewhere in the body, including the brain, and how the drugs affects quality of life.

For the entire study population of 682 patients, whose cancers ranged from stage IB to IIIA, treatment with Tagrisso cut the risk of death or cancer recurrence by 79% compared with placebo. Overall, disease-free survival at the two-year mark was 89% for patients randomized to receive Tagrisso compared with 53% of those in the placebo group. 

Of note, Herbst pointed to data that showed patients who had adjuvant chemotherapy along with osimertinib fared about the same as those who did not have chemotherapy. Data for overall survival (OS) are not yet mature, and both Herbst and a discussant acknowledged this might be challenging to evaluate going forward now that the trial has been unblinded.

Discussant David Spigel, M.D., chief scientific officer of the Sarah Cannon Research Institute in Nashville, said if asked the question he hears in the clinic-which treatment would he give his family-he would choose osimertinib. He noted the drug also performed well across different population groups.

The results have important implications for managed care. Besides high rates of recurrence, health system leaders may now have a more compelling reason to screen patients for early stage EGFR-mutated NSCLC tumors.

Adrian Kilcoyne, M.D., MBA, M.P.H., vice president for U.S. medical affairs and health economics outcomes research in oncology for AstraZeneca, said the results should shift the treatment paradigm. “What we’ve been able to demonstrate is compelling,” Kilcoyne said. “One, it’s telling us that if you hit it early, you can have very compelling results in lung cancer. “Second, in some of these patients, while they all had surgery, not all of them had adjuvant chemotherapy-half didn’t-and regardless of that you’re seeing a significant benefit.”

With results showing that early treatment brings a clear benefit if a person’s EGFR mutation is caught early, Kilcoyne was asked if this would reopen debate about who should be screened for lung cancer. He replied, “You’ve asked the million-dollar question.”

Current guidelines from the U.S. Preventive Services Task Force are based on a person’s age, smoking history, and how long ago a person quit smoking. A recent CDC study found that even under today’s restricted criteria, screening rates are poor.