ASCO: To adjuvant Tagrisso doubters—AstraZeneca's EGFR med extends survival in early lung cancer

After a massive tumor progression showing, AstraZeneca hopes new life extension data could expel whatever doubt that remains for using Tagrisso early in non-small cell lung cancer (NSCLC).

Using Tagrisso after surgery in the adjuvant setting lowered the risk of death by 51% in patients with completely resected, EGFR-mutated stage 1b to 3a NSCLC, according to an update of the phase 3 ADAURA trial presented at the 2023 American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

At five years, 88% of Tagrisso takers were still alive, versus 78% for placebo.

Given that adjuvant Tagrisso “unequivocally improves survival,” it should be the new standard of care for EGFR-mutated NSCLC, Nathan Pennell, M.D., Ph.D., from Cleveland Clinic, an invited ASCO expert, said in a statement.

Before the latest overall survival readout, post-surgical Tagrisso was already approved in early-stage NSCLC. That approval came in late 2020 based on data showing the EGFR inhibitor could cut the risk of disease recurrence or death by a whopping 83% compared with placebo in patients with stage 2 to 3a cancer. An update last year found the drug’s disease-free survival edge remained strong at 77% in stages 2 to 3a disease, or 73% in the overall stage 1 to 3a population.

Despite the massive recurrence prevention showing, some doctors remained reluctant to use Tagrisso for early-stage patients partly because the drug works so well in the metastatic setting, Mohit Manrao, AstraZeneca’s head of U.S. oncology, explained in an interview with Fierce Pharma. These doctors wanted to see whether Tagrisso could extend patients’ lives to confirm that using the drug early doesn’t undermine the well-established survival benefit that patients could enjoy if their cancers progress to an advanced stage.

The new data largely answered that question. In the ADAURA trial, nearly 90% of patients in the placebo arm who recurred got an EGFR inhibitor. Among them, about half ended up getting Tagrisso—which is widely viewed as the most powerful EGFR agent so far—at some point in their disease course, Roy Herbst, M.D., Ph.D., from Yale Cancer Center, told reporters during a press briefing.

“I happen to believe that you give your best drugs early,” Herbst said. “Why wait for a patient to have a severe side effect?”

Before the ADAURA readout, no adjuvant market existed for early-stage EGFR NSCLC, as reflected in the use of placebo in the study’s control arm. AZ’s commercial team has done most of the heavy lifting, including pushing for EGFR testing and driving referrals from surgeons to oncologists, Mohit said.

Referral rates for EGFR-mutant NSCLC have now reached nearly 90%, and 60% of those referred are getting on an adjuvant therapy. And within those treated patients, Tagrisso has a 70% share, Mohit said.

“[Overall survival] is the icing on the cake that this is the right strategy,” Mohit said.

As AZ’s top-selling drug, Tagrisso delivered $1.4 billion in sales in the first quarter of this year, a 15% increase at constant exchange rates partly thanks to increased uptake in the adjuvant setting.

AZ is also trying to move Tagrisso before surgery in the neoadjuvant setting. The NeoADAURA trial testing that approach in stage 2 or 3 EGFR-mutant NSCLC could read out next year. In addition, the phase 3 LAURA trial is expected to report data later this year on whether Tagrisso works in unresectable stage 3 disease.

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