AstraZeneca’s Tagrisso Improved Disease-Free Survival in NSCLC with EGFR Mutations by 89%

AstraZeneca released detailed data from the Phase III ADAURA clinical trial of Tagrisso (osimertinib) in early-stage epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer, demonstrating what they call “unprecedented disease-free survival.” The company is presenting the study during the plenary session of the American Society of Clinical Oncology ASCO20 Virtual Scientific Program on Sunday, May 31.

Specifically, the drug showed a statistically significant and clinically meaningful improvement in disease-free survival (DFS) in the adjuvant treatment of early-stage, meaning IB, II and IIIA, EGFRm NSCLC after complete tumor resection planned to cure. In the Stage II and IIIA group, Tagrisso decreased the risk of disease recurrence or death by 83%. In the overall trial population, Stage IB through IIIA, which was a key secondary endpoint, the drug showed a decrease in DFS of 79%.

The EGFR mutation has been identified in about 25% of lung cancer cases worldwide, but in Asia can exceed 40%.

After two years, 89% of the patients in the trial who received Tagrisso were alive and disease free compared to 53% in the placebo cohort. The DFS data were consistent across all subgroups, including surgical patients who received chemotherapy and patients who only received surgery. It was consistent in Asian and non-Asian patients.

“These data are transformative for patients with early-stage EGFR-mutated non-small cell lung cancer who face high rates of recurrence even after successful surgery and subsequent treatment with adjuvant chemotherapy,” said Roy S. Herbst, chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital in New Haven, Connecticut, and principal investigator in the ADAURA trial. “Tagrisso will provide a much-needed new treatment option that has the potential to change the practice of medicine and improve outcomes for patients in this setting.”

Tagrisso is a third-generation, irreversible EGFR-TKI with clinical activity against central nervous system (CNS) metastases. It has been approved in the U.S., Japan, China, Europe and other countries for first-line EGFRm advanced NSCLC. It is also being evaluated in the Stage III, unresectable setting in the LAURA trial, in combination with chemotherapy (FLAURA2) and in combination with new drugs to evaluate resistance to EGFR-TKIs in the SAVANNAH and ORCHARD trials.

Tagrisso is AstraZeneca’s best-selling drug, with sales in the first quarter of this year growing more than 50% to $982 million.

In April, an Independent Data Monitoring Committee recommended the ADAURA trial be unblinded two years ahead of scheduled based on the overwhelming efficacy observed. At the time of the data cut-off, the data for overall survival (OS) were not mature, so the trial will continue to evaluate OS as a secondary endpoint.

“The momentous results of the Phase III ADAURA trial for Tagrisso demonstrate for the first time in a global trial that an EGFR inhibitor can change the course of early-stage EGFR-mutated lung cancer and provide hope for a cure,” said José Baselga, AstraZeneca’s executive vice president, Oncology R&D. “We are discussing these outstanding data with regulatory authorities and look forward to bringing the benefits of Tagrisso to patients with early-stage disease.”

If approved for this indication, which seems very likely, about 60,000 more patients would be eligible for treatment. They would typically take the drug for two to three years after surgery.

In a note to clients, Sam Fazeli, an analyst with Bloomberg Intelligence, suggested that that most physicians will adopt Tagresso as standard of care for this group of patients instead of waiting for more data on OS.

Company shares jumped 3.4% at the news, which has been having a good year, with shares gaining about 50% over the last year.

In an interview with Bloomberg, Dave Fredrickson, AstraZeneca’s vice president of Global Oncology said the trial provides a “reason for more early screening to take place for lung cancer patients. The improved outcome that we’re seeking is cure.”