Health Canada Approves Osimertinib for Locally Advanced, Unresectable EGFR+ NSCLC After Chemoradiation

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Health Canada has approved osimertinib (Tagrisso) with conditions for the treatment of patients with locally advanced, unresectable stage III non–small cell lung cancer (NSCLC) whose tumors harbor EGFR exon 19 deletions or exon 21 L858R substitution mutations—either alone or with other EGFR mutations—and who did not experience disease progression during or after platinum-based chemoradiation.1 Of note, a validated test is necessary to determine EGFR mutation–positive status before a patient receives osimertinib.

The conditional approval of osimertinib was supported by data from the phase 3 LAURA trial (NCT03521154). Findings published in The New England Journal of Medicine revealed that osimertinib reduced the risk of disease progression or death by 84% vs placebo (HR, 0.16; 95% CI, 0.10-0.24; P < .001).2 The median progression-free survival (PFS) was 39.1 months compared with 5.6 months in the osimertinib and placebo arms, respectively, per blinded independent central review (BICR). Furthermore, the 12-month PFS rate was 74% (95% CI, 65%-80%) vs 22% (95% CI, 13%-32%) in the osimertinib and placebo arms, respectively. At 36 months, the overall survival (OS) rates were 84% (95% CI, 75%-89%) vs 74% (95% CI, 57%-85%) in the respective arms (HR, 0.81; 95% CI, 0.42-1.56; P = .53).

“With this approval, we’re now able to offer people living with stage III, EGFR-mutated NSCLC an oral targeted therapy,” Paul Wheatley-Price, MBChB, BSc, MD, associate professor of medicine at the University of Ottawa and medical oncologist at the Ottawa Hospital in Canada, stated in a news release.1 “The LAURA trial demonstrated that with [osimertinib], patients were able to live, on average, for more than 3 years without disease progression, which is an impressive result in this patient population.”

In September 2024, the FDA approved osimertinib for the treatment of adult patients with locally advanced, unresectable stage III NSCLC who have not experienced disease progression during or after concurrent or sequential platinum-based chemoradiation therapy and harbor EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.3 The regulatory decision was also based on data from the LAURA trial.

Regarding safety, the incidence of grade 3 or higher adverse effects (AEs) was 35% vs 12% in the osimertinib and placebo arms, respectively.2 Specifically, radiation pneumonitis was reported in 48% and 38%, respectively, of which the majority were grade 1 or 2. No new safety signals emerged. Additionally, the discontinuation rate for osimertinib due to AEs was 8.4%.1 The most common any-grade AEs occurring in at least 10% of patients included diarrhea (35.7%), rash (35.7%), paronychia (23.1%), dry skin (17.5%), stomatitis (15.4%), and pruritus (12.6%). The most common grade 3 or higher AEs caused by treatment were diarrhea (2.1%), radiation pneumonitis (2.1%), and interstitial lung disease (1.4%).

“With the approval of [osimertinib], we have a new approach of managing unresectable stage III NSCLC with EGFR mutations,” Nathalie Daaboul, MD, associate professor at the Centre intégré de cancérologie de la Montérégie at the University of Sherbrooke in Canada, stated in the news release. “The LAURA trial results reinforce the potential benefits of [osimertinib] after chemoradiation, offering hope for extended PFS and improved outcomes, which is good news for patients.”

The double-blind, placebo-controlled study enrolled patients 18 years of age or older with histologically documented NSCLC and predominantly nonsquamous pathology with locally advanced, unresectable stage III disease.4 Patients were randomly assigned to receive oral osimertinib at 80 mg or 40 mg, or placebo at the same dose levels. The primary end point was PFS by BICR; secondary end points included OS, objective response rate (ORR), duration of response, and disease control rate.

“We’re pleased to see that Health Canada has recognized the efficacy of [osimertinib] demonstrated in the LAURA study,” Shem Singh, executive director of Lung Cancer Canada, stated in the press release.1 “The ability for people with lung cancer to have more time living life without their cancer progressing is so important for their quality of life and that of their family, and this new treatment option will be welcome news for those with stage III EGFR-mutated NSCLC.”

References

1. Tagrisso approved (with conditions) in Canada for patients with unresectable, stage III EGFR-mutated non–small cell lung cancer (NSCLC). News release. BioSpace. May 21, 2025. Accessed May 22, 2025. https://www.biospace.com/press-releases/tagrisso-approved-with-conditions-in-canada-for-patients-with-unresectable-stage-iii-egfr-mutated-non-small-cell-lung-cancer-nsclc
2. Lu S, Kato T, Dong X, et al. Osimertinib after chemoradiotherapy in stage III EGFR-Mutated NSCLC. N Engl J Med. 2024;391(7):585-597. doi:10.1056/NEJMoa2402614
3. FDA approves osimertinib for locally advanced, unresectable (stage III) non–small cell lung cancer following chemoradiation therapy. FDA. September 25, 2024. Accessed May 22, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-locally-advanced-unresectable-stage-iii-non-small-cell-lung-cancer
4. A global study to assess the effects of osimertinib following chemoradiation in patients with stage III unresectable non–small cell lung cancer (LAURA). ClinicalTrials.gov. Updated April 3, 2025. Accessed May 22, 2025. https://clinicaltrials.gov/study/NCT03521154