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CHICAGO -- Newly unveiled survival data should put an end to the debate on whether to treat operable EGFR-positive non-small cell lung cancer (NSCLC) patients with osimertinib (Tagrisso) following surgery, experts said here.

Their conclusion stems from the final overall survival (OS) analysis of the ADAURA trial. In patients with completely resected stage II-IIIA disease, the 5-year OS rate improved from 73% in the placebo arm to 85% with the EGFR-targeted agent, reported Roy Herbst, MD, PhD, of Yale Cancer Center in New Haven, Connecticut, at the American Society of Clinical Oncology (ASCO) meeting.

That difference amounted to a 51% reduction in the risk for death (HR 0.49, 95% CI 0.33-0.73, P<0.001), and the OS benefit was generally consistent across disease stage in the full study population, which included stage IB patients as well.

Herbst said the findings reinforce "osimertinib as the standard of care in this group," and should sway clinicians previously sitting on the fence.

"Many surgeons, even some of my surgeon colleagues at Yale, do not recommend this," he said. "They were waiting to see, 'Does this improve survival?'"

Prior findings from the global phase III trial showed a significant improvement in disease-free survival (DFS) with osimertinib, which led to the drug's FDA approval in this patient population.

During a press briefing, ASCO-designated expert Nathan Pennell, MD, PhD, of the Cleveland Clinic Taussig Cancer Institute, noted that DFS improvements in prior trials of earlier-generation EGFR inhibitors .

Given that history, "not everyone adopted the use of osimertinib based on the disease-free survival improvement alone," he said.

But the OS data on osimertinib changes the calculus.

"It is hard for me to convey how important this finding is for the field of lung cancer, and how long it's taken to get here," said Pennell.

"We've now firmly put to rest the question about whether we should be using our most effective treatment in these people based upon biomarkers," he said. "And we should firmly close the door on one-size-fits-all treatment for people with non-small cell lung cancer."

For the past 2 decades, Pennell noted, advanced and metastatic NSCLC patients with EGFR mutations have been preferentially treated with EGFR inhibitors based on results from numerous phase III trials, he said. "People live longer and better with targeted treatment and not chemotherapy."

Yet until ADAURA, the standard of care in early-stage disease remained surgical resection followed by adjuvant chemotherapy when recommended.

In the U.S., roughly 10% to 15% of patients with NSCLC have EGFR mutations.

Subgroup analyses in the trial showed the OS advantage at 5 years favored the osimertinib arm across all stages of disease:

• Stage IB: 94% vs 88% with placebo (HR 0.44, 95% CI 0.17-1.02)
• Stage II: 85% vs 78% (HR 0.63, 95% CI 0.34-1.12)
• Stage IIIA: 85% vs 67% (HR 0.37, 95% CI 0.20-0.64)

And according to the study results, which were published simultaneously in the , the OS benefit was also consistent among patients who had received prior adjuvant chemotherapy and those who had not (HRs of 0.49 and 0.47, respectively).

From November 2015 to February 2019, the randomized 682 patients with completely resected stage IB-IIIA NSCLC to either osimertinib (80 mg per day) or placebo. Treatment was continued for 3 years or until disease recurrence or another discontinuation criteria was met. The primary endpoint was DFS, as assessed by investigators in stage II-IIIA patients, with DFS in the entire study group and OS being secondary endpoints.

In the primary study population (stage II-IIIA disease), 35 deaths in the osimertinib arm and 65 deaths in the placebo arm occurred at data-cutoff for the OS analysis. In the full population, there were 42 and 84 deaths, respectively, yielding an HR of 0.49 (95% CI 0.34-0.70, P<0.001).

As has been , patients in the study had a median age of about 63, 64% were Asian, and more than two-thirds were women. Most had a history of smoking. Participants were split roughly evenly between stages IA, II, and IIIA disease, and about 60% had received prior adjuvant chemotherapy.

During the study, more than half of patients in the placebo group went on to receive subsequent anticancer treatment, as compared with 22% in the osimertinib group. In more than 75% of cases, these were EGFR-directed agents (most commonly osimertinib).

Adverse events were consistent with the primary DFS analysis, with no new safety signals, said Herbst. One patient experienced COVID-19 pneumonia, though investigators deemed that to be unrelated to the study drug.

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