ASCO 2020: Adjuvant Osimertinib Therapy Dramatically Improves Outcomes in Non–Small Cell Lung Cancer
Disease-free survival was so much greater among patients who took the drug for up to 3 years that the study was unblinded early
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May 29, 2020—Adjuvant therapy with the tyrosine-kinase inhibitor osimertinib significantly improved disease-free survival in patients with mid- to late-stage epidermal growth factor receptor (EGFR) mutation positive non–small lung cancer, according to an interim analysis of the ADAURA trial. The results were presented virtually as part of the 2020 International Conference of the American Society of Clinical Oncology. The conference, scheduled to take place in Chicago from May 29 to June 2, was shifted to an online platform due to the COVID-19 pandemic.
“Lung cancer is the leading cause of cancer death worldwide, accounting for more than 1.7 million deaths annually,” lead author Roy S. Herbst, MD, of the Yale Cancer Center in New Haven, told Elsevier’s PracticeUpdate. “This study represents a new paradigm because it takes a third-generation, EGFR-targeted therapy, osimertinib, and moves it from the advanced setting to the early setting for patients with lung cancer who have had the disease removed with surgery. Basically, it is taking the best of both worlds. We needed to do this study because even after patients have had surgery for lung cancer, many of them will still recur.”
A total of 682 patients were included in the phase III ADAURA trial, all with a diagnosis of primary non-squamous stage IB/II/IIIA non–small cell lung cancer with confirmed EGFR mutations. All patients had undergone complete resection of their cancer, with full recovery. Post-operative chemotherapy was used if patients were deemed to be candidates, and this was delivered before patients initiated the study drug.
Patients were randomized 1:1 to receive either oral osimertinib 80 mg once daily (n = 339) or placebo (n = 343) for 3 years or until disease recurrence. They were stratified based on cancer stage, mutation type, and race. The primary endpoint was disease-free survival in stage II to IIIA patients. Secondary endpoints were disease-free survival in the total study population as well as overall survival and safety.
The study results were unblinded early because of the unexpectedly positive results, as determined by an independent data monitoring committee. The data cut-off date was January 17, 2020.
For patients with stage II to IIIA disease, 2-year disease-free survival was 90% for osimertinib patients and 44% for placebo. The hazard ratio for disease-free survival was 0.17 (95% confidence interval 0.12–0.23; P < .0001).
Among the entire patient population, 2-year disease-free survival was 89% for the osimertinib arm and 53% for the placebo arm. The hazard ratio for disease-free survival 0.21 (95% confidence interval 0.16–0.28; P < .0001).
Osimertinib was associated with improved disease-free survival among most subgroups of patients examined, including when analyses were conducted by sex, age, smoking status, EGFR mutations, and use of adjuvant chemotherapy.
Overall survival data were immature (4% maturity), with a total of 29 deaths (n = 9 for osimertinib; n = 20 for placebo) as of the data cut-off date.
The median duration of exposure for osimertinib was 22.3 months, compared with 18.4 months for placebo. Osimertinib was well-tolerated, with a safety profile consistent with previous reports. Most toxicities were low-grade. All causality adverse events occurring in ≥ 10% of patients included diarrhea (46% on osimertinib vs 19% on placebo), paronychia (25% vs 1%), dry skin (23% vs 6%), pruritis (19% vs 9%), and cough (18% vs 17%). There was only a 3% incidence of interstitial lung disease associated with osimertinib, and all cases were low-grade.
“We now have a practice-changing regimen,” said Dr. Herbst. “If you are a [lung cancer] patient with an EGFR mutation, and you have had surgery and have decided whether or not you will have adjuvant therapy, rather than just going home and waiting, we now have this drug that when taken for 3 years can reduce the chance of recurrence.”
“As someone who has treated lung cancer for 25 years, when these patients come back, the disease is in the brain, it is in the bone or the other lung. If we can prevent this, it [has the potential to] really help patients,” he continued. “This gives them more therapy that they can take to live with their lung cancer.”
The ADAURA trial was sponsored by AstraZeneca.
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