#ESMO20: AstraZeneca burnishes Tagrisso's adjuvant NSCLC profile with 'unprecedented' reduction in brain mets. Can they win over skeptics?
When AstraZeneca trumpeted “momentous” and “transformative” results for Tagrisso earlier this year at ASCO, some practitioners threw cold water on the ADAURA fervor. Sure, the disease-free survival data look good, but overall survival is the endpoint that matters when it comes to choosing adjuvant therapy for non-small cell lung cancer patients, the experts said.
The OS data still aren’t here, but AstraZeneca is back at ESMO to bolster their case with a look at brain metastasis data.
EGFR-mutant NSCLC frequently goes to the brain, with a recurrence rate as high as 40% in some studies, cancer R&D chief José Baselga explained, and it’s “one of the most devastating complications” for this group of patients. While Tagrisso’s ability to cross the blood-brain barrier findings gave them hope that it could have an effect here, he noted the findings were “quite dramatic.”
Looking at patients who were diagnosed at an early stage and had surgery to resect their tumors, Tagrisso cut the risk of CNS recurrence or death by 82%, translating to a hazard ratio of 0.18 compared with placebo (p<0.0001).
At the three-year follow-up, Baselga added, 98% of patients in the Tagrisso arm are free of brain metastases.
“This is totally unprecedented,” he told Endpoints News in a preview.
While acknowledging that comments on the need for OS data are “absolutely appropriate,” he said what is already known should be sufficient to convince physicians to change their practice.
The ADAURA data presented at ASCO marked “the most positive study in the history of adjuvant therapy” in this particular space, he said.
“I mean — it’s incredibly compelling,” he said. “As a treating physician, I would not imagine how I can not offer this to a patient. I think this in my mind clearly reinforces that it’s a new standard of care in a very powerful way.”
AstraZeneca’s goal here has been to position Tagrisso as an alternative or addition to chemotherapy that can give patients more time, post-operation, living cancer-free.
At ASCO it showcased a win on disease-free survival among patients with Stage II and IIIA disease, the primary endpoint of ADAURA, which was big enough to warrant an early stop to the trial. It achieved a 83% reduction in risk of disease recurrence or death, investigators reported then. But without OS data, lung cancer expert Jack West cautioned, you can’t rule out the possibility that patients would do just as well getting treated at relapse rather than staying on Tagrisso the whole time.
Skeptics will still have questions, but the next big move lies with the FDA. Regulators granted breakthrough therapy designation in July, boosting AstraZeneca’s hopes of moving Tagrisso — currently approved as a frontline treatment — to an even earlier line.