Sequential treatment equals long-term survival for EGFR+ NSCLC

From Targeted Oncology

Sequential afatinib (Gilotrif) followed by osimertinib (Tagrisso) has demonstrated a long-term overall survival (OS) of close to 4 years in patients with non–small cell lung cancer (NSCLC) who have EGFR deletion 19 (del19)–positive tumors and acquired T790M mutations, according to interim results released from the real-world GioTag study and published in Future Oncology.

Overall Survival Rates

Among all patients who received sequential EGFR tyrosine kinase inhibition (TKI) with afatinib followed by osimertinib and acquired an EGFRT790M mutation, after a median follow-up of 30.3 months, the median overall survival was 41.3 months. In patients with EGFR del19 tumors specifically, the median overall survival was 45.7 months.

“As many patients with this type of lung cancer eventually acquire resistance to EGFR TKIs, it’s important to consider the order of these therapies to provide patients with as many future treatment options as possible. The updated GioTag study findings provide supportive evidence that afatinib followed by osimertinib is a viable treatment sequence option for patients with EGFR mutation–positive NSCLC,” Maximilian J. Hochmair, MD, a medical pulmonologist in the Department of Internal Medicine and Pneumology of the Krankenhaus Nord – Klinik Floridsdorf in Vienna, Austria, and a coordinating investigator in the GioTag study, said in a statement.

About the GioTag Study

GioTag is an observational, retrospective, global study that assessed 204 patients with EGFR-mutant NSCLC in a real-world clinical setting. The study was conducted across 10 countries in adult patients who received frontline afatinib and acquired a T790M when they progressed on afatinib and then went on to initiate treatment with osimertinib. Data were collected from medical chart reviews and electronic health records.

The study group reflected a broad population of patients with EGFR-mutant NSCLC treated in a real-world clinical setting; 15.2% of patients had an ECOG performance status of ≥2 and 10.3% had central nervous system metastases. As of the start of afatinib treatment, 73.5% of patients had a del19 mutation, 26.0% had an L858R mutation, and one patient had both.

Afatinib was started at the standard FDA-approved initial dose of 40 mg/day in 83.7% and 98.0% started osimertinib at the approved dose of 80 mg/day.

As of data cutoff in April 2019, 41.9% of patients had died, 12.8% were lost to follow-up, and 45.3% were still alive including 31.0% who were still on treatment with osimertinib.

The median time to treatment failure (TTF) for sequential afatinib and osimertinib was 28.1 months. Among patients with del19-positive tumors, the median time to treatment failure was 30.6 months. With osimertinib treatment, the median time to treatment failure was 15.6 months in all patients and 16.4 months in patients with del19 mutations.

At 2 years, the overall survival rate was 80% in the overall population and 82% in patients with del19 mutations.
In patients who received the approved starting dose of 40 mg/day of afatinib, the median overall survival was 45.3 months , the 2-year overall survival rate was 82%, and the median time to treatment failure was 28.1 months.

Optimal Sequence of Treatment

“The continued clinical development of new EGFR TKIs provides additional treatment options for patients with EGFR-mutant NSCLC, and raises questions about their optimal sequence. Given that, as yet, no established targeted treatment options are available following failure of osimertinib, there is an argument for reserving osimertinib for second-line use after second-generation EGFR TKIs. Real-world data from the GioTag study supports the argument for sequential use of afatinib and osimertinib for patients with EGFR-mutant NSCLC who are del19-positive,” Victoria Zazulina, MD, corporate vice president and global head of oncology, medicine, at Boehringer Ingelheim, the company developing afatinib, said in a statement.
The final analysis of the GioTag study is expected in early 2020, which will include updated data from Asian and European countries.