Afatinib Followed by Osimertinib Achieves Nearly 4-Year OS in EGFR T790M+ Non–Small Cell Lung Cancer

Sequential afatinib followed by osimertinib led to a median overall survival of 47.6 months in patients with EGFR T790M–positive non–small cell lung cancer, according to results from the real-world study, GioTag.

Sequential afatinib (Gilotrif) followed by osimertinib (Tagrisso) led to a median overall survival (OS) of 47.6 months in patients with EGFR T790M–positive non–small cell lung cancer (NSCLC), according to results from the real-world study, GioTag (NCT03370770).1 This OS result is consistent with the prior global primary analysis of the GioTag and an interim analysis conducted in the United States.

“Developing resistance to EGFR TKIs is, unfortunately, an expected outcome for many people with this specific lung cancer, and strategies for sequencing treatments continue to evolve with the use of TKIs in clinical practice,” said Balazs Halmos, MD, chief of thoracic/head and neck oncology at Montefiore Medical Center. “These real-world data provide further insight into the overall survival associated with afatinib and subsequent osimertinib treatment and reinforce that previous findings may have application in the US treatment setting for patients with T790M acquired resistance.”

In addition to demonstrating good OS data, GioTag also showed a combined median time to treatment failure (TTF) of 28.4 months with afatinib plus osimertinib. Across the subgroups evaluated in the study, TTF was consistent with the overall population. Specifically, patients with EGFR deletion 19 (del19) alterations had a median TTF of 30.3 months, those with ECOG performance status of 0 to 1 had a median TTF of 32.7 months, and patients aged 65 years or older had a median TTF of 34.1 months.

According to the most recent information on the study, patients received afatinib for a median of 11.3 months (90% CI, 10.3-12.0) and received osimertinib for a median of 15.0 months (90% CI, 13.4-16.4).

In the prior US analysis, the 2-year OS rate observed with patients who started afatinib was 82% and the median OS was 45.3 months (90% CI, 37.6-47.6). The OS benefit was carried into the subgroup of patients with del19-positive disease (45.7 months [90% CI, 45.3-47.6]). The median TTF in this analysis was 28.1 months (90% CI, 27.6-33.8) for patients with del19-positive tumors.2

“These real-world data offer additional evidence that afatinib prior to osimertinib may be an important consideration for patients with EGFR mutation-positive NSCLC. Cancer can take away so much and understanding strategies such as treatment sequencing is one way Boehringer Ingelheim is taking cancer on,” said Bjoern Rueter, MD, Therapeutic Area Head Oncology, at Boehringer Ingelheim, in a statement.

GioTag is a real-world retrospective, observational study looking at initial treatment with afatinib followed by osimertinib in patients with del19 and L858R EGFR-mutated NSCLC who have acquired T790M mutations. The study is evaluating TTF as the primary end point, and type and proportion of acquired resistance mutation after osimertinib as the secondary end point.

To be eligible, patients were required to have EGFR-mutant NSCLC that harbors del19 or L858R at the start of frontline therapy, a T790M mutation at the start of second-line therapy, have started treatment with osimertinib, and be at least 18 years of age.


1. Additional analysis of real-world data confirms sequential Gilotrif® followed by osimertinib provided a median overall survival of nearly four years in U.S.-treated patients with EGFR mutation-positive NSCLC. News release. Boehringer Ingelheim. August 10, 2020. Accessed August 10, 2020.

2. Hochmair M, Morabito A, Hao D, et al. Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: updated analysis of the observational GioTag study. Future Oncol. 2019; 15(25):2905-2914. doi:10.2217/fon-2019-0346