A 50% improvement on the time patients could live without disease progression would typically be considered remarkable for a new drug. AstraZeneca’s Tagrisso just delivered an 84% improvement.
Tagrisso mounted that massive progression-free survival benefit when compared with placebo in unresectable stage 3 EGFR-mutated non-small cell lung cancer (NSCLC) after definitive chemoradiotherapy in the phase 3 LAURA trial. The trial’s results, when presented Sunday, June 2, during the plenary session at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, received a standing ovation from the audience.
“Starting as soon as this becomes available—the label gets expanded—this will be how patients are treated at wherever they can get access to this drug,” David Spiegel, M.D., an ASCO expert from the Sarah Cannon Research Institute, said about the LAURA data during a press conference Saturday.
The trial win in unresectable stage 3 disease adds to Tagrisso’s position as the leading EGFR inhibitor in metastatic NSCLC and as a postsurgical adjuvant therapy for resectable tumors.
The LAURA trial found that patients who received Tagrisso lived a median 39.1 months without disease progression versus 5.6 months for placebo. Two years after treatment, 6% of patients on Tagrisso developed brain metastases compared with 28% in the control group. The tumor progression benefit was seen across key subgroups, including in stage 3a and in stage 3b or 3c tumors, according to the full results published in The New England Journal of Medicine.
Data on patients’ life expectancy remain immature but already showed a favorable trend suggesting a preliminary 19% reduction in the risk of death for Tagrisso versus placebo. That’s despite 81% of patients in the placebo arm having received Tagrisso following disease progression. Investigators expect to report mature overall survival data in about 18 months to two years, Suresh Ramalingam, M.D., from Emory University and principal investigator of the trial, said during Saturday’s press briefing.
With an FDA approval now all but in AZ’s bag, Tagrisso can also fill a gap left by the company’s PD-L1 immunotherapy Imfinzi, which has been viewed as the standard of care in stage 3 NSCLC based on findings from the phase 3 PACIFIC trial. In a post hoc analysis of a small number of patients with EGFR mutations enrolled in that study, Imfinzi was only linked to a marginal 9% reduction in the risk of progression or death.
Imfinzi has its own positive data set—and a potential label expansion down the line—to celebrate at the ASCO conference.
Imfinzi reduced the risk of death by 27% compared with placebo in patients with limited-stage small cell lung cancer (LS-SCLC) following concurrent chemoradiotherapy, according to results from the phase 3 ADRIATIC study presented during the plenary session of the ASCO annual meeting.
The ADRIATIC trial hit that dual primary endpoint early during an interview analysis. The estimated median overall survival was 55.9 months for Imfinzi, versus 33.4 months for placebo.
On the other dual primary endpoint, Imfinzi also cut the risk of disease progression or death by 24% over placebo. Patients who got Imfinzi went a median 16.6 months without progression, versus 9.2 months for the placebo group.
LS-SCLC accounts for about 30% of SCLC cases but has not seen new treatment in about 40 years, Cristian Massacesi, M.D., AZ’s chief medical officer and oncology chief development officer, said during an interview with Fierce Pharma.
Industry watchers’ focus of the ADRIATIC readout is likely on the data that were not presented at ASCO. The study has a third arm evaluating Imfinzi alongside AZ’s CTLA4 inhibitor Imjudo. Although Imfinzi monotherapy has already read out positively, the Imfinzi-Imjudo combination arm has not, raising the question of Imjudo’s role in this disease setting.
The lack of an Imfinzi-Imjudo readout shouldn’t be viewed as a sign of weaker efficacy, Spiegel, who leads the ADRIATIC study, suggested during Saturday’s press conference.
The combo arm has simply not been analyzed, Spiegel said. The trial is designed to analyze the dual primary endpoints for Imfinzi versus placebo comparison, and then the combo-versus-placebo analysis as a secondary endpoint, according to Spiegel. He also noted that the trial was amended to expand the Imfinzi monotherapy comparison while shrinking the combo group.
Imjudo does not have the best track record in lung cancer and was so far only successful in the tumor type as part of a combination with Imfinzi and chemotherapy in first-line metastatic NSCLC. And its showing there was not competitive against other PD-1 inhibitors.
AZ’s Massacesi suggested that Imjudo may be able to add some longer-term benefit as its additive effect has been observed later in trials in other disease settings. But he declined to comment on what magnitude of benefit would AZ consider meaningful for Imjudo on top of Imfinzi in the ADRIATIC trial.