Results from the Phase 3 AURA study show that Tagrisso (osimertinib) is clinically superior to the combination of Alimta (pemetrexed) plus platinum-based chemotherapy in the treatment of certain patients with non-small-cell lung cancer (NSCLC).
Those patients had T790M-positive advanced NSCLC whose disease progressed after treatment with first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).
The U.S. FDA granted accelerated approval of Tagrisso in November 2015 for patients with this specific type of NSCLC. This Phase 3 trial confirmed the results of earlier studies.
The study with the results, “Osimertinib or Platinum–Pemetrexed in EGFR T790M-Positive Lung Cancer,” was published in the New England Journal of Medicine.
Tagrisso is an oral, irreversible EGFR-TKI developed by AstraZeneca for cancers with EGFR mutations. The drug is selective for both EGFR and T790M resistance mutations with activity in the central nervous system (CNS).
To assess the effectiveness of Tagrisso in patients with confirmed T790M-positive advanced NSCLC after first-line EGFR-TKI therapy, Tony S. Mok, MD, from the Chinese University of Hong Kong, and colleagues conducted the Phase 3 confirmatory, randomized, open-label, international, AURA3 trial (NCT02151981).
The study enrolled 419 participants who were randomly assigned to oral Tagrisso (80 mg once daily) or intravenous Alimta (500 mg per square meter of body surface area) plus Paraplatin (carboplatin) or Platinol (cisplatin; 75 mg per square meter of body-surface area) every three weeks for up to six cycles.
The primary effectiveness endpoint was progression-free survival (PFS) as determined by the investigator according to RECIST 1.1 (Response Evaluation Criteria in Solid Tumours). Secondary endpoints included objective response rate, response duration, disease control rate, tumor shrinkage, overall survival, patient-reported outcomes, and profiles of safety and side effects.
The researchers found that median PFS was significantly longer in the Tagrisso group compared to those receiving platinum-based chemo plus Alimta (10.1 months versus 4.4 months, respectively).
Similarly, objective response rate (ORR) was also significantly higher in the Tagrisso group (71%) compared to the control group (31%).
The researchers found that among the 144 patients who had metastases in the CNS, Tagrisso more than doubled patients’ median PFS compared to that seen in the control group (8.5 months versus 4.2 months, respectively).
Adverse events occurred in 273 of 279 patients assigned Tagrisso and in 135 of 136 in the platinum–Alimta combo group. In the Tagrisso group, the most commonly reported adverse events were diarrhea, rash, dry skin, and nail disease, while in the platinum–Alimta group they included mostly nausea, reduced appetite, constipation, and anemia.
“[Tagrisso] had significantly greater efficacy than platinum therapy plus pemetrexed in patients with T790M-positive advanced non-small-cell lung cancer (including those with CNS metastases), in whom disease had progressed during first-line EGFR-TKI therapy,” the researchers wrote.