Findings from the ADAURA trial argue for starting treatment with the AstraZeneca drug early, says Yale’s Roy Herbst, M.D., Ph.D., the principal investigator.
Eagerly awaited “unprecedented” results from the ADAURA trial offer hope to some patients: One daily Tagrisso (osimertinib) pill cut the risk of death from lung cancer in half.
In staid, scientific language, the researchers reported that adjuvant therapy with AstraZeneca’s Tagrisso resulted in significantly longer disease-free survival for some patients with resected, epidermal-growth-factor receptor (EGFR)–mutated, stage 1B to 3A non–small-cell lung cancer, with or without previous adjuvant chemotherapy.
But in talking about it, the researchers were more effusive.
The study results are “thrilling,” said Roy Herbst, M.D., Ph.D., deputy director of the Yale Cancer Center, the co-lead author and principal investigator of the ADAURA trial, who presented the findings at the American Society of Clinical Oncology’s (ASCO) annual meeting in Chicago earlier this month.
“When we treat the cancer early, we prevent the cancer from spreading to the brain, to the liver, to the bones. In this trial, we took advantage of the efficacy of osimertinib, used it earlier, and it resulted in a really phenomenal impact on survival. That’s practice-changing, and it helps people live longer with lung cancer. I’m very excited to be part of this research.”
Payers may be concerned, however, about the cost of broader use of Tagrisso. It is currently priced — using the wholesale acquisition cost before any rebates or discounts — to cost about $193,000 a year. Patients may take the drug for many years.
The FDA approved Tagrisso for late-stage lung cancer in 2015. These latest findings, Herbst said, “really taking personalized therapy from advanced metastatic disease and moving it all the way to the earliest stages of lung cancer treatment.”
Preliminary findings, released in 2020, had demonstrated such “substantial” benefit that the independent data monitoring committee recommended early unblinding of the phase 3 trial. “We expected this would work,” Herbst said of the recent findings, “but not this well.”
In an interview with The Guardian, Nathan A. Pennell, M.D., Ph.D., associate professor and director of the Lung Cancer Medical Oncology Program at the Cleveland Clinic Taussig Cancer Institute, and ASCO expert, said, “It’s hard to convey how important this finding is and how long it’s taken to get here. This shows an unequivocal, highly significant improvement in survival.”
The international placebo-controlled study, which had a follow-up period of up to 6.8 years, involved 682 patients with an EGFR mutation called T790M. About 1 in 4 lung cancer cases have that mutation. The patients had undergone surgery; some had also completed chemotherapy. Half of the patients took 80 mg of Tagrisso once a day for three years (unless they had to discontinue it).
After five years, 88% of the patients in the Tagrisso group were alive compared with 78% of the placebo patients. Even more encouraging, 85% of the patients in the Tagrisso group who had stage 3 cancers survived compared with 67% of those randomized to receive the placebo. The survival benefit “was observed consistently” across all study subgroups and regardless of whether the patient had received chemotherapy.
In addition to improving disease-free survival, Tagrisso reduced the risk of local and distant metastases and improved central nervous system disease-free survival. Herbst said the results added “huge weight” to earlier findings that showed the pill also halves the risk of a recurrence.
Not everyone diagnosed with lung cancer is tested for the EGFR mutation, but Herbst told The Guardian, given the study’s findings, “this further reinforces the need to identify these patients with available biomarkers at the time of diagnosis and before treatment begins.”