AstraZeneca is raising its defenses against Johnson & Johnson in a fierce competition in EGFR-mutated non-small cell lung cancer.
Following an FDA approval last year based on a tumor progression benefit, AZ said Monday that its Tagrisso combination with chemotherapy extended patients’ lives compared with Tagrisso alone in first-line advanced EGFR-mutated NSCLC.
The readout came from the final overall survival analysis of the phase 3 Flaura2 trial, which had previously shown that the Tagrisso-chemo combo reduced the risk of disease progression or death by 38% versus Tagrisso monotherapy. The latest update found that the combo’s overall survival improvement was statistically significant and clinically meaningful, AZ said.
The detailed results remain under wraps, but AZ said the survival benefit was consistent with that from an interim analysis. At 41% data maturity, Tagrisso plus chemo pared down the risk of death by 25%, which, at the time, did not reach statistical significance. At that interim look, the Tagrisso-chemo regimen’s overall survival advantage appeared to be narrowing after 39 months.
“These exciting overall survival results add to the extensive evidence supporting Tagrisso as the backbone therapy in EGFR-mutated lung cancer,” AZ’s oncology R&D chief, Susan Galbraith, Ph.D., said in a July 21 statement. “With its strong survival benefit and tolerable safety profile, this combination has the potential to help patients live longer while maintaining their quality of life on treatment.”
Adding chemotherapy is one way for AZ to bolster Tagrisso as J&J challenges the longtime EGFR king with its combination of Rybrevant and Lazcluze.
Earlier this year, J&J showed that Rybrevant plus Lazcluze can significantly extend overall survival versus Tagrisso in first-line EGFR-mutated NSCLC. The death risk reduction coincidentally also mounted to 25%, according to data from the phase 3 Mariposa trial.
Despite Rybrevant and Lazcluze’s better efficacy showing, the regimen’s added toxicity and Tagrisso’s convenience as a pill are expected to be hurdles on J&J’s quest.
Even after the Tagrisso-chemo cocktail's overall survival win, the Flaura2 trial’s principal investigator, Pasi Jänne, M.D., Ph.D., from the Dana-Farber Cancer Institute, said the updated results support Tagrisso, “either as monotherapy or in combination with chemotherapy, as standard of care” in the first-line setting, according to AZ’s July 21 release.
In the first six months of 2025, sales from the J&J combo reached $320 million, compared with $116 million during the same period last year.
AZ has not reported its second-quarter financial results. In the first quarter, Tagrisso’s worldwide sales increased 5% to $1.68 billion, partly thanks to increased demand in stage 3 unresectable EGFR-mutated NSCLC.
As to the competition between Rybrevant-Lazcluze and Tagrisso-chemo, J&J has argued that chemotherapies, thanks to their toxicity, should be reserved for subsequent treatment rather than upfront in the first-line setting.
Flaura2 did not impose any restrictions on the choice of subsequent treatment after disease progression, Jänne noted.