Tagrisso (osimertinib) demonstrates superiority over chemotherapy in EGFR T790M mutation-positive non-small cell lung cancer.
AstraZeneca presented data from the AURA3 trial that is supportive of Tagrisso (osimertinib) potentially becoming the new standard of care for second-line treatment of patients with epidermal growth factor receptor (EGFR) T790M mutation-positive metastatic non-small cell lung cancer (NSCLC).
The first randomized Phase III data showed that Tagrisso second-line therapy improved progression-free survival (PFS) by 5.7 months compared with standard platinum-based doublet chemotherapy (hazard ratio [HR]=0.30; 95% confidence interval (CI): 0.23, 0.41; p<0.001).
The results were presented at the 17th World Conference on Lung Cancer (WCLC) in Vienna, Austria, hosted by the International Association for the Study of Lung Cancer, and published simultaneously online in The New England Journal of Medicine.
“The confirmatory Phase III data suggest the potential for Tagrisso to replace chemotherapy as the standard of care for patients who have progressed following EGFR tyrosine kinase inhibitor treatment,” Sean Bohen, executive vice president, global medicines development and chief medical officer at AstraZeneca, said. “As lung cancer is the most common type of cancer to spread to the brain, it is also encouraging to see the activity of Tagrisso in patients with central nervous system metastases whose prognosis is often particularly poor.”
AURA3 data showed Tagrisso offered a statistically significant improvement in PFS versus standard platinum-based doublet chemotherapy (10.1 months vs 4.4 months, hazard ratio [HR] 0.30; 95% confidence interval (CI): 0.23, 0.41; p<0.001). In an investigator-assessed, pre-specified exploratory subgroup analysis of 34% of patients with central nervous system (CNS) metastases at baseline, PFS was 8.5 months with Tagrisso versus 4.2 months with platinum-pemetrexed chemotherapy (HR 0.32; 95% CI: 0.21, 0.49).
“The results of AURA3 are not only statistically significant, but clinically meaningful because it is the first time a targeted medicine like Tagrisso has shown improvement in progression-free survival over standard platinum-pemetrexed chemotherapy,” Dr. Vassiliki A Papadimitrakopoulou of the University of Texas MD Anderson Cancer Center said. “It’s very rewarding to be able to give this type of news to patients, as it highlights the major advances we are making in targeted lung cancer treatments.”
According to Professor Tony Mok of the Chinese University of Hong Kong, “The superiority of Tagrisso in progression free survival and response rate over platinum-pemetrexed chemotherapy suggests we may be moving towards a new standard of care for patients with resistance to EGFR TKI. With the publication of the AURA3 data, clinicians should perform T790M mutation testing to ensure Tagrisso be given to patients who are most likely to benefit.”
The AURA3 safety data for Tagrisso were in line with previous experience. Grade ≥3 drug-related adverse events (AEs) were reported in 6% of patients (n=16) treated with Tagrisso and 34% (n=46) treated with platinum-based doublet chemotherapy. The most common drug-related AEs in the Tagrisso group, were diarrhea (29% overall; 1% Grade ≥3) and rash (28% overall; <1% Grade ≥3) and, in the chemotherapy group, they were nausea (47% overall; 3% Grade ≥3) and decreased appetite (32% overall; 3% Grade ≥3).
The data for AURA3 are consistent with those previously presented in the Phase II trials, AURA2 and AURA extension. This consistency extends to testing of tissue and plasma samples for the detection of the EGFR T790M resistance mutation. In AURA3, approximately half of patients with T790M in tumor tissue also had the T790M mutation detected in plasma. Clinical benefits were reported with Tagrisso compared to platinum-based doublet chemotherapy, irrespective of whether the T790M mutation was identified by plasma ctDNA or tissue testing. Plasma testing for the presence of the mutation is recommended only when a tumor biopsy cannot be obtained. If this mutation is not detected in a plasma specimen, re-evaluate the feasibility of biopsy for tumor tissue testing.
Tagrisso was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in November 2015 for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, who have progressed on or after EGFR TKI therapy. In the EU, Tagrisso was granted conditional marketing authorization for adult patients with locally advanced or metastatic EGFR T790M NSCLC, irrespective of previous EGFR TKI treatment by the European Medicines Agency (EMA) in February 2016.
In addition, Tagrisso received approval in Japan in March 2016 for the treatment of patients with EGFR T790M mutation-positive inoperable or recurrent NSCLC that is resistant to EGFR TKI therapy, and it is currently under fast track review in China, where nearly half of lung cancer patients are thought to have the EGFR mutation.
(Source: Business Wire)
Filed Under: Drug Discovery