Tagrisso Approved for First-Line Tx of EGFR Mutation Positive Advanced NSCLC

The Food and Drug Administration (FDA) has approved Tagrisso^® (osimertinib) in combination with chemotherapy for the treatment of adults with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC).

The approval was based on data from the phase 3 FLAURA2 study (ClinicalTrials.gov Identifier: NCT04035486), which included 557 patients with EGFR exon 19 deletion or exon 21 L858R mutation-positive locally advanced or metastatic NSCLC, who had no prior systemic therapy for advanced disease. Study participants were randomly assigned 1:1 to receive osimertinib monotherapy or in combination with chemotherapy (pemetrexed) plus cisplatin or carboplatin every 3 weeks for 4 cycles, followed by osimertinib with pemetrexed maintenance every 3 weeks. The primary endpoint was progression free survival (PFS).

Results showed that treatment with osimertinib plus chemotherapy achieved a statistically significant improvement in PFS vs osimertinib monotherapy (hazard ratio [HR], 0.62 [95% CI, 0.49-0.79]; P <.0001). Median PFS was extended by 8.8 months in the combination arm vs monotherapy (25.5 months vs 16.7 months, by investigator assessment). Based on blinded independent central review, the combination extended median PFS by 9.5 months (HR, 0.62 [95% CI, 0.48-0.80]; P =.0002). While overall survival data were immature at the time of analysis, there was no trend towards a detriment observed.

Among patients with central nervous system metastases, the objective response rate (ORR) for osimertinib plus chemotherapy was 80% (95% CI, 64-91), with 48% having complete response and 33% having partial response vs 76% (95% CI, 60-89) for osimertinib monotherapy, with 16% having complete response and 61% having partial response.

The most common adverse reactions (incidence ≥20%) for osimertinib plus chemotherapy were leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased blood creatinine.

Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber Cancer Institute and principal investigator for the trial, said: “This approval based on the unprecedented data from FLAURA2 brings a critical new treatment option to patients with advanced EGFR-mutated non-small cell lung cancer. Now, with the choice of two highly effective osimertinib-based options, physicians can better tailor treatment to an individual’s needs and help ensure the best possible outcome for each patient.”

Tagrisso, a kinase inhibitor, is also indicated for the first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations; patients with metastatic EGFR T790M mutation-positive NSCLC who have progressed on or after EGFR tyrosine kinase inhibitor therapy; and adjuvant treatment after tumor resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations.

Tagrisso is available as 40mg and 80mg strength tablets in 30-count bottles.