Osimertinib Shows Significant OS Benefit in Patients With Resected, EGFRm NSCLC

Adjuvant osimertinib with or without chemotherapy substantially improved overall survival (OS) vs placebo among patients with resected EGFR-mutated (EGFRm) non–small cell lung cancer (NSCLC) in the phase 3 ADAURA study. Results of the final OS analysis are being presented during the plenary session Sunday at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

Osimertinib (Tagrisso, AstraZeneca) demonstrated improved disease-free survival (DFS)—the main study end point—in the primary analysis of ADAURA, which was featured in the plenary session at the 2020 ASCO Annual Meeting. In addition to OS improvement, the updated data show sustained DFS and central nervous system (CNS) DFS at 2 additional years of follow-up.

The third-generation EGFR-tyrosine kinase inhibitor was the first targeted agent to be FDA approved for adjuvant treatment of resected EGFR-mutated NSCLC in 2020. But the lack of OS data at that time was a sticking point for some, lead study author Roy S. Herbst, MD, PhD, deputy director of Yale Cancer Center and assistant dean for translational research at Yale School of Medicine, explained during a press briefing ahead of the 2023 plenary session.

“Despite the fact that we had these [DFS] data and this drug is approved in the US and many countries, overall survival is considered the main gold standard for treatment efficacy, and everyone was keenly awaiting these data,” Herbst said. “There are some places that have not approved it yet. There are some physicians, many surgeons—even some of my surgeon colleagues at Yale—[who] do not recommend this, because they're waiting to see, does this improve survival?”

Osimertinib demonstrated unprecedented and highly statistically significant OS with or without chemotherapy in the updated analysis, and the findings were consistent across patient subgroups. A tolerable safety profile in line with previous reports was also seen over the course of the extended follow-up. These findings are poised to broaden access to osimertinib in this patient population.

"Now, with the unequivocal, highly clinically significant improvement in overall survival at 5 years, with 3 years of osimertinib across stage I, II, and IIIA, we've now firmly put to rest of the question about whether we should be using our most effective treatment in these people based upon biomarkers," said ASCO expert Nathan Pennell, MD, PhD, FASCO. "And we should firmly close the door on one-size-fits all treatment for people with non–small cell lung cancer."

In the ADAURA trial, a total of 682 patients with stage IB-IIIA EGFRm NSCLC were randomized to receive either osimertinib (n = 339) or a placebo (n = 343) once daily until disease recurrence, treatment completion at 3 years, or until treatment discontinuation due to meeting discontinuation criteria.

In the overall population, the HR for OS was 0.49 (95% CI, 0.34, 0.70; P < .0001; 124/682 events, 18% maturity), a finding mirrored in patients with stage II-IIIA disease (HR, 0.49; 95% CI, 0.33-0.73; P = .0004; 100/470 events, 21% maturity).

In the overall population, the 5-year OS rates in the osimertinib and placebo cohorts were 88% and 78%, respectively. Median follow-up for OS was 60.4 months in the osimertinib cohort and 59.4 months in the placebo cohort. In patients with II-IIIA disease, the 5-year OS rate was 85% in the osimertinib cohort, compared with 73% in the placebo cohort at median follow-ups of 59.9 months and 56.2 months, respectively.

“It's the first global phase 3 study to demonstrate statistically significant and clinically meaningful DFS and OS benefit with targeted therapy in this patient population, reinforcing osimertinib as the standard of care in this group,” Herbst said.

Approximately 12%-25% of lung cancers in the United States and 30%-40% of lung cancers in Asia have EGFR mutations, but patients who could benefit from targeted therapies, including osimertinib, must first be identified, Herbst said. Therefore, spreading awareness of the importance of genomic testing for targetable mutations and minimizing socioeconomic barriers to testing is crucial.

“One of the things we're hoping will come out from these data is that we have new therapies that we can offer to patients. If we screen, if we find these mutations, we can make a difference—but only if we find those patients,” Herbst said.


Reference

Herbst RS, Tsuboi M, John T, et al. Overall survival analysis from the ADAURA trial of adjuvant osimertinib in patients with resected EGFR mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC). Presented at: American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, IL. Accessed June 4, 2023. Abstract LBA3.