Certain early-stage lung cancer patients who take the drug Tagrisso (osimertinib) after surgery may dramatically boost their survival odds, study results suggest, with those in a recent trial showing a 51% lower risk of death after three years on the medication.
The trial included 682 patients with non-small-cell lung cancer (NSCLC), the most common type of lung cancer, whose tumours had mutations in the epidermal growth factor receptor (EGFR) gene. This gene can cause rapid cell growth and help cancer spread more quickly, reports Everyday Health.
All of the patients underwent cancer surgery, then were randomly assigned to take a daily pill with either a placebo or an 80mg dose of AstraZeneca’s Tagrisso, a targeted therapy that’s designed to treat tumours with mutated EGFR genes.
After three years, the patients who took Tagrisso had a 51% lower risk of death from early-stage lung cancer, showed the results, published in the New England Journal of Medicine and presented at the annual meeting of the American Society of Clinical Oncology.
The five-year overall survival rate was 88% for patients who received Tagrisso, compared with 78% on a placebo. There were too few deaths in the study to determine exactly how long the survival benefit might ultimately extend.
While Tagrisso is already FDA-approved for the patients who took it in the study, the results offer fresh evidence that the drug can work even for patients with smaller, less advanced tumours, said Dr Roy Herbst, the principal investigator on the study and the deputy director of the Yale Cancer Centre in New Haven, Connecticut.
“The results are impressive. We’re moving this effective drug therapy into the earliest stages of disease,” he said.
Tagrisso was first approved in 2018 as an initial treatment for patients with advanced lung cancer whose tumours had EGFR mutations. The US Food and Drug Administration (FDA) expanded the approval in 2020, clearing the drug for use as an adjuvant, or follow-up, therapy for earlier-stage lung cancer patients with EGFR mutations.
“With this approval, patients may be treated with this targeted therapy in an earlier and potentially more curative stage of non-small-cell lung cancer,” said Dr Richard Pazdur, director of the FDA’s Oncology Centre of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Centre for Drug Evaluation and Research,
Oncologists, take note
Beyond this, the findings may also encourage any oncologist – who was on the fence about using Tagrisso for early-stage tumours – to move in this direction, said Dr Nathan Pennell, a professor and the director of the lung cancer medical oncology programme at the Cleveland Clinic Taussig Cancer Institute in Ohio.
That’s because the FDA-approval of Tagrisso for early-stage lung cancer patients wasn’t based on overall survival rates. It was based instead on what’s known as disease-free survival (DFS), or how long patients live without cancer coming back after initial treatment. Tagrisso reduced cancer recurrence by 80% in data reviewed by the FDA to approve the drug for early-stage lung cancer.
“For many oncologists. this will simply affirm what they were already doing in offering adjuvant Tagrisso based on the prior DFS benefit,” Pennell added. “But there were some who waited for the overall survival results, and this should change their practice.”
Study details
Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC
Masahiro Tsuboi, Roy Herbst, Thomas John, Terufumi Kato, Margarita Majem, Christian Grohé, Jie Wang, Jonathan Goldman, Shun Lu, Wu-Chou Su, Filippo de Marinis, Frances Shepherd, et al.,for the ADAURA Investigators*
Published in the New England Journal of Medicine on 4 June 2023
Abstract
Background
Among patients with resected, epidermal growth factor receptor (EGFR)–mutated, stage IB to IIIA non–small-cell lung cancer (NSCLC), adjuvant osimertinib therapy, with or without previous adjuvant chemotherapy, resulted in significantly longer disease-free survival than placebo in the ADAURA trial. We report the results of the planned final analysis of overall survival.
Methods
In this phase 3, double-blind trial, we randomly assigned eligible patients in a 1:1 ratio to receive osimertinib (80 mg once daily) or placebo until disease recurrence was observed, the trial regimen was completed (3 years), or a discontinuation criterion was met. The primary end point was investigator-assessed disease-free survival among patients with stage II to IIIA disease. Secondary end points included disease-free survival among patients with stage IB to IIIA disease, overall survival, and safety.
Results
Of 682 patients who underwent randomisation, 339 received osimertinib and 343 received placebo. Among patients with stage II to IIIA disease, the 5-year overall survival was 85% in the osimertinib group and 73% in the placebo group (overall hazard ratio for death, 0.49; 95.03% confidence interval [CI], 0.33 to 0.73; P<0.001). In the overall population (patients with stage IB to IIIA disease), the 5-year overall survival was 88% in the osimertinib group and 78% in the placebo group (overall hazard ratio for death, 0.49; 95.03% CI, 0.34 to 0.70; P<0.001). One new serious adverse event, pneumonia related to coronavirus disease 2019, was reported after the previously published data-cutoff date (the event was not considered by the investigator to be related to the trial regimen, and the patient fully recovered). Adjuvant osimertinib had a safety profile consistent with that in the primary analysis.
Conclusions
Adjuvant osimertinib provided a significant overall survival benefit among patients with completely resected, EGFR-mutated, stage IB to IIIA NSCLC.
Everyday Health article – Lung Cancer Pill Cuts Death Risk by Half in New Study (Open access)
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