Drug Combination Leads to 4-Year Survival in Patients with Lung Cancer

Article

A regimen of afatinib as a first-line treatment followed by osimertinib in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer was found to significantly improve overall survival.

The results of an interim analysis from the GioTag study has shown that initiating a regimen of afatinib (Gilotif) followed by osimertinib led to an overall survival (OS) of nearly 4 years in patients with non-small cell lung cancer with epidermal growth factor receptor (EGFR) Del19 and T790M positive tumors.

The observational and unblinded study, which previously reported 2 and 2.5 year OS rates, examined the impact of treatment with afatinib followed by osimertinib in patients with Del19/L858R EGFR mutation-positive (EGFR M+) non-small cell lung cancer (NSCLC) with acquired T790M mutations. These mutations are the most common mechanism of resistance to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs).

“It’s important to consider sequencing of therapies to provide patients with as many future treatment options given that many of them with this type of lung cancer eventually acquire resistance to EGFR TKIs,” said Balazs Halmos, MD, chief of Thoracic/Head and Neck Oncology at Montefiore Medical Center.

The study included 94 of the initial 126 participants, all of whom had available electronic health records. Researchers began by using electronic data to facilitate rapid analysis. After a median follow-up of 30.3 months, median OS was approximately 3.5 years (41.3 months) in patients with acquired EGFR T790M-positive NSCLC treated in a real-world clinical setting. The updated 2-year overall survival was 80%.

The OS was particularly promising in patients with Del19-positive tumors at the onset of afatinib treatment. In these patients, median OS was 45.7 months and the 2-year OS rate was 82%.

Updated median time on treatment for sequential afatinib and osimertinib was 28.1 months overall and 30.6 months in patients with Del19-positive tumors. Median time on osimertinib treatment following an afatinib regimen was 15.6 months and 16.4 months for Del19 mutations.

“Real-world data continue to inform the use and sequencing of cancer treatments,” Halmos said. “The updated GioTag study findings add to a growing body of evidence that afatinib followed by osimertinib is a viable treatment sequence and associated with prolonged overall survival for patients.”

The study authors concluded by noting that the continued clinical development of new EGFR TKIs provides additional treatment options for patients with EGFR M+ NSCLC and raises questions about their optimal sequence. As osimertinib failed as a first-line treatment, the authors noted that there may be reason to reserve osimertinib for second-line use after second-generation EGFR TKIs.

This interim analysis is the first of a 2-step process and a final analysis is planned for early 2020, which will include updated information from Asian and European countries.

Reference

  • Hochmair J, Maximilian, et. al. Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: updated analysis of the observational GioTag study. August 2, 2019. https://doi.org/10.2217/fon-2019-0346. Accessed August 4, 2019.

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