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Results from AZENT Trial have been just published on European Journal of Cancer

We are happy to announce that the results from the AZENT trial are now available in the European Journal of Cancer. AZENT is a MEDSIR’s sponsored trial, designed and scientifically led by Dr. Rafael Rosell from Institut Català d’Oncologia (ICO) and Institut d’Investigació en Ciències de la Salut Germans Trias I Pujol (IGTP). This study investigated the efficacy and safety of first-line osimertinib in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC) harboring a coexisting low allelic fraction of EGFR Thr790Met mutation.

NSCLC represents an epithelial tumor accounting for 85% of all lung malignancies. NSCLCs are characterized by a low sensitivity to chemotherapy, but the identification of activating mutations in the gene encoding the EGFR tyrosine kinase (TK) led to the development of targeted therapy with small-molecule EGFR tyrosine kinase inhibitors (TKIs) that revolutionized the treatment landscape of these tumors. In fact, somatic, activating mutations in the TK domain of EGFR are present in about 15% of Caucasian and nearly 50% of Asian patients with advanced NSCLC.

First generation of TKIs showed great results compared to platinum-based chemotherapy, however the majority of patients ended up developing resistance to the treatment and experiencing progressive disease. Since the most common resistance mechanism resulted from the development of EGFR T790M mutation in exon 20, third generation of TKIs have been specifically designed to overcome this mechanism.

Osimertinib is a third generation TKI that selectively targets sensitizing EGFR mutations, as well as the T790M resistance mutation. Although EGFR T790M has been considered an acquired mutation, Dr. Rosell’s team, as well as other groups, have been able to identify that T790M can also pre-exist in some patients before the administration of any TKIs, diminishing the effects of other EGFR inhibitors not targeting this specific mutation. Considering this background, the AZENT study focused on all those patients harboring sensitizing EGFR coexisting with T790M mutations, with the final aim of customizing treatment with T790M-specific inhibitors.

AZENT was a multicentric, single arm, open label, phase II study, designed with a Simon’s two stage optimal design. Through this trial design we could assesses if the rate of responses during the first stage is sufficiently high to recommend the drug to go to the next stage with a greater sample size. A total of 22 patients with advanced NSCLC with centrally confirmed EGFR mutation and with a coexisting

low allelic fraction of Thr790Met were accrued from 6 different sites in Spain during the first stage. Patients received osimertinib 80mg/day on a continuous dosing schedule, until disease progression, death, intolerable toxicity, or withdrawal of consent.

When the preliminary data were assessed, 50% of patients were still on treatment, being the median duration of osimertinib treatment of 18.2 months. Objective responses were achieved on 17 out of 22 patients (77.3%) including 4 out of 22 patients with complete response, meeting the efficacy criteria to move towards the next stage. Progression free survival (PFS) was also promising with a median PFS of 23.1 months in the general population, compared to 18.9 months reported in the FLAURA study, which supported the approval of osimertinib in advanced NSCLC patients. Osimertinib also demonstrated an excellent safety profile with grade 3–4 adverse events that occurred in only 4 out of 22 patients. However, since early study termination prevented full recruitment, the above findings cannot be conclusive.

Results from the AZENT trial can be considered encouraging, despite their observational nature. The significant benefit and long-lasting response attained compared with prior studies of first-line or second-line osimertinib treatment would support this regimen for EGFR-mutant NSCLC with Thr790Met mut ations, confirming the importance of molecular screening in order to administer the most adequate treatment to each patient” said Dr. Rosell, senior author of this manuscript.

The AZENT trial was run thanks to the financial support of AstraZeneca.

Don’t hesitate to contact us for further information about this trial or any of our ongoing trials.

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