AstraZeneca is confident that Tagrisso shows great promise of becoming the first line treatment for metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) following encouraging results during a recent Phase III trial.
Tagrisso is an irreversible EGFR inhibitor. The 80mg tablet is approved in Canada and the U.S. During the drug’s Phase III trial involving patients with locally-advanced or metastatic EGFR T790M mutation-positive NSCLC, Tagrisso reduced the risk of progression or death by more than half, with consistent benefit across all subgroups, including patients with and without brain metastases.
“The data are truly exciting. Until now, even with the therapeutic advances offered by the first- and second-generation EGFR inhibitors, less than 20 per cent of EGFR mutation-positive NSCLC patients survive for five years,” said Sean Bohen, executive Vice-president, global medicines development and chief medical officer at AstraZeneca. “The data suggest early and sustained benefit with Tagrisso that has the potential to significantly impact long-term patient outcomes and help address the considerable unmet need that remains.”
On average, 57 Canadians die from lung cancer every day. That amounts to more than 20,000 each year. More people die from lung cancer than breast cancer, colorectal cancer and prostate cancer combined.
NSCLC is the most common form of lung cancer and accounts for 85 to 90 per cent of all lung cancers in Canada. Often diagnosed in late stage, fewer than 17 per cent of patients diagnosed with NSCLC will live more than five years following diagnosis.Ethnicity can increase the risk for genetic mutations in NSCLC. In Caucasian populations, 10 to 15 per cent of all NSCLC diagnoses are EGFR mutation-positive, but this climbs to 30 to 40 per cent in people of Asian background with NSCLC. NSCLC patients with the EGFR T790M mutation are more likely to be female and to have never smoked
“Not only did the trial demonstrate a robust improvement in efficacy with osimertinib when compared to other commonly-used EGFR inhibitors, the side effects profile was also more favourable with osimertinib,” according to Dr Suresh S. Ramalingam, principal investigator of the Phase III trial, from the Winship Cancer Institute of Emory University, in Atlanta.
According to AstraZeneca, Tagrisso showed superior disease progression compared to other medications.
Additional highlights from the trial data include:
- Patients on Tagrisso had less than half the risk of progression or death compared with patients on erlotinib or gefitinib (hazard ratio [HR] 0.46; 95 per cent confidence interval [CI] 0.37-0.57; p<0.0001). The median PFS was 18.9 months for patients on Tagrisso vs.10.2 months for patients in the comparator arm.
- Clinically-meaningful preliminary overall survival (OS) data at 25 per cent maturity: The hazard ratio for OS was 0.63 (95 per cent CI: 0.45-0.88; p=0.0068) favouring Tagrisso. Overall survival data were 25 per cent mature at the time of the interim analysis (21 per cent of the patients on Tagrisso had died and 30 per cent of the patients on the comparator arm had died). The p-value of 0.0068 was not below the threshold of 0.0015 required for statistical significance at the current level of maturity. A final OS analysis is planned at a later maturity.
- PFS improvements consistent across subgroups: Improvements in PFS with Tagrisso were consistent across all pre-specified patient subgroups, with at least a 40 per cent reduction in the risk of progression or death, including in patients with/without central nervous system (CNS) metastases at study entry, Asian/non-Asian patients, patients with/without prior smoking history, and patients with exon 19 deletion/L858R.
- Patients treated with Tagrisso had more than double the median duration of response (DoR) than those in the comparator arm (17.2 months vs. 8.5 months), and an ORR (a measurement of tumour shrinkage) of 80 per cent vs. 76 per cent with the comparator arm (odds ratio 1.28 [0.85-1.93], p=0.2335).
“In Canada, Tagrisso is already approved for use in the second-line setting, yet patients do not have public access to this new medicine,” said says Dr Glenwood Goss, professor of medicine, University of Ottawa, and director of clinical and translational research at the Ottawa Hospital Cancer Centre. FLAURA data provides further evidence of the benefits of this targeted therapy, underscoring why patients need access as soon as possible.”
The trial data “provides further evidence of the benefits of this targeted therapy, underscoring why patients need access as soon as possible,” said Goss.