Real-World Data Show Long-Term Survival With Sequential Afatinib and Osimertinib in EGFR+ NSCLC

Sequential afatinib followed by osimertinib has demonstrated a long-term overall survival of close to 4 years in patients with non&ndash;small cell lung cancer who have <em>EGFR </em>deletion 19&ndash;positive tumors and acquired T790M mutations, according to interim results released from the real-world GioTag study.

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 haveEGFRdeletion 19 (del19)—positive tumors and acquired T790M mutations, according to interim results released from the real-world GioTag study and published inFuture Oncology.1,2

Among all patients (n = 203) who received sequential EGFR tyrosine kinase inhibition (TKI) with afatinib followed by osimertinib and acquired anEGFRT790M mutation, after a median follow-up of 30.3 months (range, 24.0-36.8), the median OS was 41.3 months (90% CI, 36.8-46.3). In patients withEGFRdel19 tumors specifically (n = 149), the median OS was 45.7 months (90% CI, 45.3-51.5).

“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 withEGFRmutation—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.

GioTag is an observational, retrospective, global study that assessed 204 patients withEGFR-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 withEGFR-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 (90% CI, 26.8-30.3). Among patients with del19-positive tumors, the median TTF was 30.6 months (90% CI, 27.6-32.0). With osimertinib treatment, the median TTF was 15.6 months (90% CI, 13.8-17.1) in all patients and 16.4 months (90% CI, 14.9-17.9) in patients with del19 mutations.

At 2 years, the OS 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 OS was 45.3 months (90% CI, 37.6-47.6), the 2-year OS rate was 82%, and the median TTF was 28.1 months.

“The continued clinical development of new EGFR TKIs provides additional treatment options for patients withEGFR-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 withEGFR-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.


  1. Updated real-world data shows Giotrif&reg;/Gilotrif&reg; (afatinib) followed by osimertinib provided a median overall survival of up to almost four years in patients with EGFR Del19 and T790M mutation-positive NSCLC [news release]. Ingelheim, Germany: Boehringer Ingelheim; August 2, 2019. Accessed August 2, 2019.
  2. Hochmair MJ, Morabito A, Hao D, et al. Sequential afatinib and osimertinib in patients withEGFRmutation-positive non-small-cell lung cancer: updated analysis of the observational GioTag study [published online August 2, 2019].Future Oncol.doi: 10.2217/fon-2019-0346.