Osimertinib after surgery reduces risk for death by 51% in resected EGFR-mutant NSCLC
Click Here to Manage Email Alerts
Key takeaways:
- Patients with stage IB to IIIA non-small cell lung cancer that received osimertinib after surgery had a 51% lower risk of death compared to placebo.
- OS benefit observed across all predefined subgroups treated with adjuvant osimertinib.
CHICAGO — Adjuvant osimertinib conferred a significant OS benefit vs. placebo among patients with resected, EGFR-mutant, stage IB to IIIA non-small cell lung cancer, according to results of the ADAURA trial presented at ASCO Annual Meeting.
The findings, set to be published in The New England Journal of Medicine, provided further evidence that the addition of osimertinib (Tagrisso, AstraZeneca) to standard treatment of surgery, with and without chemotherapy, should remain the current standard of care for this patient population, according to researchers.
“I was hoping that there would be a certain positive survival benefit; the HR for DFS presented at ASCO 3 years ago was 0.17, for an 83% improvement, but we have a 51% decreased risk for death with this data here,” Roy S. Herbst, MD, PhD, deputy director of Yale Cancer Center and assistant dean for translational research at Yale School of Medicine, told Healio. “The drug has already been approved and it’s being used in the adjuvant setting now. As investigators, we were all quite pleased with the data and it’s the biggest thrill for me to present it this year.”
Background and methodology
Previous data from ADAURA showed adjuvant osimertinib resulted in longer DFS among patients with resected, EGFR-mutated, stage IB to IIIA NSCLC with or without adjuvant chemotherapy. At ASCO, Herbst reported results of a final analysis of OS.
The study included 682 patients randomly assigned in a 1:1 ratio to 80 mg osimertinib once daily (n = 339) or placebo (n = 343). Treatment continued until disease recurrence, treatment completion at 3 years or discontinuation criterion was met.
The groups had a similar average patient age (64 years osimertinib vs. 62 years placebo).
Investigator-assessed DFS among patients with stage II to stage IIIA disease served as the primary endpoint. DFS among the overall study population, OS and safety served as secondary endpoints.
Median follow-up for OS was 61.7 months for the osimertinib group and 60.4 months for the placebo group among patients with stage II to stage IIIA disease and 61.5 months for both groups among the overall population.
Results
Researchers reported 5-year OS rates among patients with stage II to stage IIIA disease of 85% in the osimertinib group and 73% in the placebo group (HR = 0.49; 95.03% CI, 0.33-0.73).
In the overall population, researchers reported 5-year OS rates of 88% in the osimertinib group and 78% in the placebo group (HR = 0.49; 95% CI, 0.34-0.7). The OS results favored osimertinib across subgroups.
Approximately 66% of patients in the osimertinib group and 41% of patients in the placebo group completed the planned treatment duration of 3 years.
Adverse events led to treatment discontinuation for 13% of patients in the osimertinib group and 3% of patients in the placebo group.
Researchers reported a safety profile for adjuvant osimertinib consistent with that observed in the primary analysis. No new adverse events of special interest occurred, Herbst said.
Next steps
Researchers plan to build off this data with additional studies assessing the efficacy and effectiveness of osimertinib in various other settings and stages for this patient population, according to Herbst.
“We are already doing NeoADAURA, with there being a lot of push to do therapy in the neoadjuvant setting,” Herbst told Healio. “There’s also LAURA, which is looking at the drug after chemoradiation, and ADAURA 2, where we’re trying to move it to smaller tumors, and we’re also expanding to looking at 5 years of the drug.
“I really hope policymakers will see this and approve the drug, physicians will see this and discuss it in their multimodality tumor boards so that they can use the drug early, and that patients will see it, as well,” he added.
References:
- Herbst RS, et al. Abstract LBA3. Presented at: ASCO Annual Meeting 2023; June 2-6, 2023; Chicago.
- Osimertinib after surgery significantly improves survival in patients with resected EGFR-mutated non-small cell lung cancer(ASCO press release). Available at: https://old-prod.asco.org/about-asco/press-center/news-releases/osimertinib-after-surgery-significantly-improves-survival. Accessed June 4, 2023. Published June 4, 2023.
Perspective
Back to Top
Joshua K. Sabari, MD
Targeted therapies have revolutionized solid tumor oncology with multiple FDA approved therapies in the metastatic front-line setting leading to improvement in overall survival and quality of life for our patients. Osimertinib, a 3rd generation EGFR tyrosine kinase inhibitor is approved in the front-line metastatic setting in patients with activating EGFR mutations leading to clinically meaningful improvement in progression free survival and overall survival. As we improve care for patients in the stage IV setting, we are now looking at how these therapeutics may improve cure rates in patients with early-stage disease. Early-stage lung cancer, stage IB-IIIA is common, and patients are typically treated with resection followed by adjuvant chemotherapy with minimal improvements in recurrence free survival. Utilizing biomarker selected treatment strategies in this patient population is critical to drive better outcomes.
The ADUARA trial, a randomized phase III study of adjuvant osimertinib vs placebo in patients with resected stage IB-IIIA Lung adenocarcinoma post adjuvant chemotherapy changed practice for patients with early-stage disease demonstrating clear improvement in disease free survival and CNS recurrence. The recent presentation by Dr. Herbst, solidifies the role for osimertinib in the adjuvant setting with a clinically significant improvement in overall survival as well as central nervous system recurrence of disease. This study highlights the importance of broad molecular testing in patients with early-stage non-small cell lung cancer in an effort to match patients to targeted therapies that lead to improvement in survival.
Perspective
Back to Top
These are pretty awesome results. The OS data are incredibly compelling, and that is tremendously important for the population of patients with EGFR-positive disease. In the United States, this probably is practice confirming. In other countries, where regulatory agencies require OS data before a drug is reimbursed, I believe this will be practice changing.
Beyond that, ADAURA signals to the scientific community the importance of conducting these bold studies and the tremendous impact they can have.
In terms of where we go from here, the role of osimertinib in the neoadjuvant setting already is being studied. For patients with smaller tumors — let’s say stage IA — the question will be whether the addition of osimertinib can really move the needle. When you look at the recurrence rates across ADAURA, the smaller the tumor, the less chance of the tumor coming back. So I'm not sure we need to think about evaluating this for patients with smaller tumors. Instead, we should be asking if we can spare those patients an additional treatment.
We have made tremendous progress in lung cancer, but one area where progress has been lacking is patient prognostication — specifically, which patients need more therapy and which patients may not need as much. This is one question still out from ADAURA. If this were in the neoadjuvant setting, where a patient finishes a finite course of treatment and proceeds to surgery, it’d be a different conversation. But with ADAURA, the important question is whether the benefit of osimertinib in the entire intent-to-treat population is equal, and we know it is not. There is a sufficient group of patients who do not benefit from osimertinib. There also is a group who would’ve done well without osimertinib, and the same likely goes for adjuvant chemotherapy. In the adjuvant setting, how can we prognosticate better to identify patients for whom we need to intensify treatment? Just as important, can we identify those who can be spared an adjuvant therapy that won’t provide benefit, along with the financial toxicity and potential side effect toxicity?
Collapse
Herbst RS, et al. Abstract LBA3. Presented at: ASCO Annual Meeting 2023; June 2-6, 2023: Chicago.
Click Here to Manage Email Alerts