EU Approves Tagrisso Plus Chemotherapy for EGFR-Mutant Advanced Lung Cancer

AstraZeneca's Tagrisso, in combination with pemetrexed and platinum-based chemotherapy, has been granted approval by the European Union for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) that exhibit specific EGFR mutations. This decision, endorsed by the European Commission, is based on the positive opinion of the Committee for Medicinal Products for Human Use and data from the FLAURA2 Phase III trial, which demonstrated the benefits of the combination therapy in extending progression-free survival (PFS).

The FLAURA2 trial, published in The New England Journal of Medicine, provided compelling evidence that combining Tagrisso with chemotherapy significantly reduces the risk of disease progression or death by 38% compared to Tagrisso alone. The hazard ratio in this comparison was 0.62, with a 95% confidence interval of 0.49-0.79 and a p-value of less than 0.0001. Patients receiving the combination therapy experienced a median PFS of 25.5 months, marking an 8.8-month improvement over the 16.7 months seen with Tagrisso monotherapy. Blinded independent central review (BICR) results supported these findings, showing a median PFS of 29.4 months for the combination therapy versus 19.9 months for monotherapy, with a hazard ratio of 0.62 and a nominal p-value of 0.0002.

Notably, a prespecified exploratory analysis of patients with brain metastases at the trial's start indicated a 42% reduction in the risk of CNS disease progression or death with the combination therapy compared to Tagrisso alone. At the two-year follow-up mark, 74% of patients on the combination therapy had not experienced CNS disease progression or death, compared to 54% of those on monotherapy.

While the overall survival (OS) data remain immature at the second interim analysis, with 41% maturity, there is an observed trend favoring the combination treatment. The hazard ratio for OS was 0.75, with a 95% confidence interval of 0.57-0.97. These promising results continue to be evaluated, with OS being a key secondary endpoint of the trial.

Dr. David Planchard, a thoracic oncologist at Gustave Roussy Institute of Oncology and principal investigator of the trial, emphasized the significance of these findings for patients with EGFR-mutated lung cancer in Europe. He noted that the combination therapy provides a new first-line treatment option, building on the established efficacy of osimertinib monotherapy by offering a notable nine-month improvement in progression-free survival.

Dave Fredrickson, Executive Vice President of AstraZeneca's Oncology Business Unit, highlighted that this approval underscores Tagrisso's role as a foundational therapy for EGFR-mutated lung cancer, either as monotherapy or in combination with chemotherapy. This is especially crucial for patients with aggressive disease, including those with brain metastases and L858R mutations.

The safety profile of Tagrisso combined with chemotherapy aligns with the known profiles of the individual drugs. However, higher adverse event rates were observed in the combination therapy group, primarily due to chemotherapy-related adverse events. Discontinuation rates due to adverse events were 11% for the combination therapy and 6% for monotherapy.

Tagrisso is globally approved in over 110 countries, including the US, EU, China, and Japan, for various indications related to EGFR-mutated NSCLC. The combination therapy with chemotherapy is also approved in several countries for first-line treatment of advanced EGFR-mutated NSCLC. Additionally, Tagrisso is currently under review for treating unresectable Stage III EGFR-mutated NSCLC based on the LAURA Phase III trial.