GioTag Update: Final OS Promising for Sequential Afatinib Following Osimertinib in EGFR+ NSCLC

Sequential afatinib (Gilotrif) followed by osimertinib (Tagrisso) led to encouraging outcomes in patients with deletion 19 (del19) or L858R epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC), according to the final analysis results from the real-world study, GioTag.¹

“The real-world data reported here represent the most mature analysis of overall survival (OS) with sequential afatinib and osimertinib to date. The final GioTag results support the results of our previous analyses, that sequential afatinib and osimertinib treatment could be a feasible and effective therapeutic strategy in a broad, real-world population of patients with EGFR mutation-positive NSCLC who acquire T790M,” said Maximilian J. Hochmair, MD, medical oncologist, Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute

The analysis included 204 patients who were required to have EGFR-mutant disease 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. The study included 15.2% with ECOG performance status of 2 or more and 10.3% central nervous systems metastases, which are 2 groups unlikely to be evaluated in clinical trial settings. The study population was predominantly Caucasian (58.8%) but had a considerable number of Asian patients (24.5%) as well as African American patients (8.8%). At the start of treatment in the study, del19 was detected in 73.5% of patients, and L858R was detected in 26.0%.²

Follow-up lasted for a median of 33.9 months, and the median time on treatment was 27.7 months (90% CI, 26.7-29.9). Time on treatment did vary for Asian patients who were on treatment for a median of 37.1 months (90% CI, 28.1-40.3). Time on treatment was also different for patients with del19 mutations at a median of 30.0 months (90% CI, 27.6-31.9).

The median OS achieved with sequential afatinib followed by osimertinib was 37.6 months (90% CI, 35.5-41.3) in the overall study population. The 2-year survival rate was 80%. Notably, Asian patients have a slightly longer OS at 44.8 months (90% CI, 36.9-45.0) and in patients with del19 mutations and the median PS was 41.6 months (90% CI, 36.9-45.0). In patients who were Asian and had del19-positive disease, the median OS was 45.7 months (90% CI, 38.2-57.8).

In terms of survival in patients with other characteristics, those with brain metastases had a median OS of 31.0 months, patients aged 65 years or older have a median OS of 36.9 months, and those with an ECOG performance score of 2 or higher had a median OS of 32.0 months. The clinical effectiveness of sequential afatinib was overall consistent across the subgroup included in the study.

Hochmair et al also found that the median time from discontinuation of osimertinib to death was 5.6 months (90% CI, 4.3-8.0).

GioTag (NCT03370770) primarily explored time to treatment in patients with EGFR-mutant NSCLC with del19 or L858R. The secondary end point of the study was the type and proportion of acquired resistance mutations after osimertinib. Patients from 10 countries, including Austria, Canada, Israel, Italy, Japan, Singapore, Slovenia, Spain, Taiwan, and the United States, participated in the study.^1,2

“Resistance to first-line EGFR TKI therapy is an inevitability, making subsequent treatment options following disease progression a key consideration. While no prospective OS data are currently available to compare different sequential regimens of EGFR TKIs, the final GioTag study data provide important insight into the use of afatinib followed by osimertinib. The GioTag data suggest a potential for prolonged periods of time on non-chemotherapy treatment in patients with EGFR del19 who develop T790M mutation-positive tumors,¹ stated, Bjoern Rueter, MD, Therapeutic Area head Oncology, USA, at Boehringer Ingelheim.

_Reference:

_{Final analysis of the observational GioTag study: Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small cell lung cancer. News release. Boehringer Ingelheim. September 2, 2020. Accessed September 2, 2020. https://bit.ly/31QqMly}

_{Hochmair MJ, Morabito A. Hao D, et al. Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: final analysis of the GioTag study. Future Med. Published online August 28, 2020. doi:10.2217/fon-2020-0740}