KEY TAKEAWAYS
- FLAURA2 is a phase III trial that assessed the effectiveness and safety of initial treatment with osimertinib in combination with platinum-pemetrexed chemotherapy.
- In the safety run-in, adult patients diagnosed with EGFR mutation-positive locally advanced or metastatic NSCLC were orally administered a daily dose of 80mg.
- The outcome of the safety run-in phase showed that the combination of osimertinib and chemotherapy exhibited a manageable safety and tolerability profile in patients with advanced or metastatic non-small cell lung cancer harboring EGFR mutations.
- The patient population consisted of 73% Asian individuals, 63% of whom were female, with a median age of 61.
- The safety run-in of FLAURA2 provides support for additional evaluation in the randomized phase III assessment of the effectiveness and safety of initial treatment with osimertinib
The FLAURA2 (NCT04035486) phase III trial assessed the effectiveness and safety of initial treatment with osimertinib in combination with platinum-pemetrexed chemotherapy compared to osimertinib alone in patients with advanced/metastatic non-small-cell lung cancer (NSCLC) who have a mutation in the epidermal growth factor receptor (EGFRm). The safety run-in, as documented, evaluated the safety and tolerability of osimertinib in conjunction with chemotherapy before the randomized phase III assessment. Adult patients diagnosed with epidermal growth factor receptor mutation-positive locally advanced or metastatic non-small cell lung cancer were orally administered 80mg of osimertinib daily. This was accompanied by intravenous cisplatin at a dose of 75mg/m2 or intravenous carboplatin with a target area under the curve of 5. Additionally, pemetrexed was administered at 500mg/m2 every three weeks for four cycles. The prescribed treatment regimen consisted of osimertinib at a dose of 80 mg once daily and pemetrexed at 500 mg/m2 once every three weeks until either progression or discontinuation of therapy. The principal aim was to assess the safety and tolerability of the osimertinib-chemotherapy amalgamation.
A total of 30 patients, with 15 in each group, were administered treatment. The patient population consisted of 73% Asian individuals, 63% of whom were female, with a median age of 61 years (range: 45-84 years). Twenty-seven patients (90%) reported experiencing adverse events (AEs). The incidence of AEs was 100% for osimertinib-carboplatin-pemetrexed and 80% for osimertinib-cisplatin-pemetrexed. The prevalent adverse events observed were constipation (60%) in the osimertinib-carboplatin-pemetrexed group and nausea (60%) in the osimertinib-cisplatin-pemetrexed group. In each cohort, 20% of subjects reported experiencing significant adverse events (AEs). There was no discernible pattern of adverse events resulting in dosage adjustments or cessation of treatment. A single patient discontinued all study treatments, including osimertinib, due to pneumonitis, which met the discontinuation criterion specific to the study. The hematologic toxicities observed were within the expected range and were effectively managed. The combination of osimertinib and chemotherapy exhibited a manageable safety and tolerability profile in patients with advanced or metastatic non-small cell lung cancer harboring EGFR mutations. These findings provide support for additional evaluation in the randomized phase of FLAURA2.
Source: https://pubmed.ncbi.nlm.nih.gov/34543864/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04035486
Planchard D, Feng PH, Karaseva N, Kim SW, Kim TM, Lee CK, Poltoratskiy A, Yanagitani N, Marshall R, Huang X, Howarth P, Jänne PA, Kobayashi K. Osimertinib plus platinum-pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study. ESMO Open. 2021 Oct;6(5):100271. doi: 10.1016/j.esmoop.2021.100271. Epub 2021 Sep 17. PMID: 34543864; PMCID: PMC8453202.
