Osimertinib Compared Docetaxel-bevacizumab as Third-line Treatment in EGFR T790M Mutated Non-Small-Cell Lung Cancer
Mené sur 147 patients atteints d'un cancer du poumon non à petites cellules de stade avancé et présentant la mutation T790 M du gène EGFR, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'osimertinib et d'un traitement combinant docétaxel et bévacizumab en traitement de troisième ligne
Objective : To compare the efficacy and toxicity of osimertinib versus docetaxel-bevacizumab as third-line treatment in EGFR T790 M mutated NSCLC. Methods : In this phase 3, open-label, three-center study, we randomly assigned (1:1) previously treated with TKI-chemotherapy or chemotherapy-TKI recurrent or metastatic advanced non-squamous lung cancer patients into two groups. These patients had acquired EGFR T790 M resistance mutation confirmed by tumor tissues or serum. One group received oral osimertinib (80 mg/day) and the other group received intravenous infusion docetaxel (75 mg/m2) and bevacizumab (7.5 mg/kg) every 21 days until disease progression, unacceptable toxic effects or patient death. The primary endpoint of this study was progression-free survival (PFS) and the secondary endpoints were response rates, toxicities and overall survival (OS). This trial was registered with ClinicalTrials.gov, number NCT02959749. Results : A total of 147 patients were treated. Among them, 74 were enrolled in the osimertinib group and 73 were in the docetaxel-bevacizumab group. The median progression-free survival was 10.20 months in the osimertinib group versus 2.95 months in the docetaxel-bevacizumab group (hazard ratio 0.23; 95% confidence interval [CI], 0.12–0.38; P < 0.001). The overall response rate in the osimertinib group was significantly better than in the docetaxel-bevacizumab group (61.6%; 95% CI, 55.5–67.7 versus 8.3%; 95% CI, 1.3–15.3; p < 0.001). Because all the progressed patients in the docetaxel-bevacizumab group crossed over to the osimertinib group, there was no significant difference in the median OS between two groups at the time of last follow-up (hazard ratio 0.79; 95% CI, 0.38–1.16; P = 0.551). The main grade 3 or 4 toxic effects were diarrhea (2.7%) and interstitial lung disease (1.4%) in the osimertinib group and alopecia (15.3%), anorexia (12.5%), neutropenia (9.7%) and nausea (8.3%) in the docetaxel-bevacizumab group. Conclusions : Osimertinib had higher response rate, longer PFS and milder side effects than docetaxel-bevacizumab in third-line therapy in patients with EGFR T790 M positive advanced NSCLC.
Lung Cancer 2018