Sequential Afatinib and Osimertinib Shows Sustained Real-World OS Benefit in EGFR+ NSCLC

Treatment with afatinib (Gilotrif) followed by osimertinib (Tagrisso) led to a median overall survival of 41.3 months and a 2-year OS rate of 80% in patients with EGFR T790M-positive non–small cell lung cancer in a real-world setting.

Victoria Zazulina, MD

Treatment with afatinib (Gilotrif) followed by osimertinib (Tagrisso) led to a median overall survival (OS) of 41.3 months and a 2-year OS rate of 80% in patients with EGFR T790M-positive non—small cell lung cancer (NSCLC) in a real-world setting, according to updated interim results of the phase III GioTag study.1,2

Moreover, in patients with Del19-positive tumors, the median OS was 45.7 months (90% CI, 45.3-51.5) and the 2-year OS rate was 82%. The median time on treatment for sequential afatinib and osimertinib was 28.1 months, and 30.6 months in those with exon 19 deletions (Del19). Following treatment with afatinib, the median time on osimertinib was 15.6 months overall and 16.4 months for those with Del19.

A final analysis planned for early 2020 will include updated data from Asian and European countries, according to Boehringer Ingelheim Oncology, the developer of afatinib.

“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,” study investigator Maximilian J. Hochmair, MD, medical pulmonologist, Department of Internal Medicine and Pneumology, Krankenhaus Nord, Klinik Floridsdorf, stated in a press release. “The updated GioTag study findings provide supportive evidence that afatinib followed by osimertinib is a viable treatment sequence option for patients with EGFR-[mutant] NSCLC.”

Afatinib is currently indicated for the treatment of patients with metastatic NSCLC with Del19 or exon 21 L858R substitutions, for patients with squamous histology following progression on a platinum-based chemotherapy, and for the treatment of patients with metastatic NSCLC whose tumors harbor uncommon EGFR alterations in L861Q, G719X, and/or S768I.

Osimertinib is approved by the FDA as a first-line treatment for patients with NSCLC whose tumors harbor EGFR mutations (Del19 or exon 21 L858R substitution mutations), and also for those with EGFR T790M—positive NSCLC whose disease has progressed following an EGFR TKI.

In the retrospective, observational, and unblinded GioTag trial, sequential afatinib and osimertinib was administered in 203 patients with EGFR-mutant NSCLC with acquired T790M mutations. The majority of patients received the approved starting dose of afatinib at 40 mg daily (83.7% ) and osimertinib at 80 mg daily (98%).

More than half of patients were Caucasian (58.8%), 24.5% of patients were Asians, and 8.8% were African Americans (8.8%). A total 15.2% of patients had an ECOG performance status of at least 2, and 10.3% had CNS metastases. Additionally, 149 (73.5%) patients had Del19-positive tumors and 26.0% had L858R mutations; 1 patient had both abnormalities.

The first part of the two-stage process comprised a subsequent analysis that assessed updated data from a patient subset with available electronic health records. The final analysis of the study will incorporate data from manual chart reviews of an additional 29 patients and is anticipated in early 2020.

All patients must have received osimertinib ≥10 months prior to study enrollment to avoid early censoring and ensure mature data. The primary endpoint was time-to-treatment failure (TTF), and an OS analysis was exploratory.

By April 2019, 85 patients (41.9%) had died, 26 (12.8%) were lost to follow-up, and 92 patients (45.3%) were alive, which included 63 (31.0%) who remained on osimertinib treatment. One patient was excluded due to conflicting data reports.

Results showed that the updated median TTF with afatinib and osimertinib was 28.1 months (90% CI, 26.8-30.3). In patients with Del19-positive tumors, the median TTF was 30.6 months (90% CI, 27.6-32.0).

At a median follow-up of 30.3 months, the overall median OS was 41.3 months (90% CI, 36.8-46.3) and was 45.7 months (90% CI, 45.3-51.5) in patients with Del19-positive tumors.

“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,”

Victoria Zazulina, MD, corporate vice president and global head of oncology, medicine, at Boehringer Ingelheim, stated in the press release. “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.”


  1. Updated real-world data shows Giotrif/Gilotrif (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. Boehringer Ingelheim. Published August 2, 2019. Accessed August 2, 2019.
  2. Hochmair MJ, 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 [published online ahead of print August 2, 2019]. Future Med. doi: 10.2217/fon-2019-0346.