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GioTag: a real-world study of afatinib followed by osimertinib

Retrospective Study of Sequential Therapy with Afatinib Followed by Osimertinib in EGFR Mutation-Positive NSCLC

A global, non-interventional chart review based on existing medical records of patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC) who were treated with first-line afatinib*, developed the T790M mutation and were then treated with second-line osimertinib.

Trial CT.gov-Identifier: NCT03370770


  • EGFR mutation-positive advanced NSCLC
  • Common EGFR mutations (Del19, L858R) at start of first-line treatment with afatinib
  • Data were collected only in patients who had started osimertinib ≥10 months prior to data entry
  • Patients with active brain metastases at the start of either therapy were excluded


First-line afatinib followed by osimertinib in patients who acquired the T790M mutation

Outcome measures

Primary outcome measure:

  • Time on treatment, defined as the time from the first dose of afatinib to the time of the last dose of osimertinib or death

Secondary outcome measure:

  • The type and proportion of acquired resistance mechanisms after osimertinib treatment


Patient characteristics and treatment received

The patient population included a range of ethnicities with 120 (59%) Caucasians, 50 (25%) Asians and 18 (9%) African-American patients. At the start of afatinib treatment, Eastern Cooperative Oncology Group performance status (ECOG PS) was 0, 1 or ≥2 in 43 (21%), 110 (54%) and 31 (15%) patients, respectively. One hundred and fifty (74%) patients had a Del19 mutation, 53 (26%) had the L858R mutation and 21 (10%) had stable brain metastases.

The predominant reason for discontinuation of afatinib was progressive disease (n=190; 93%). At the time of database lock (29 June 2018), 106 (52%) patients had discontinued osimertinib, with progressive disease being the most common reason for discontinuation (n=98; 92%). A further 98 patients were continuing osimertinib treatment.


Time on treatment

After a median follow-up of 28.2 months, the median overall time on sequential afatinib and osimertinib treatment was 27.6 months (90% confidence interval [CI]: 25.9–31.3).


Time on treatment with sequential afatinib and osimertinib

GioTag study: time on treatment with sequential afatinib and osimertinib

Clinical benefit of sequential afatinib and osimertinib was observed across patient subgroups categorised by ethnicity, age, EGFR mutation type, presence of brain metastases and ECOG PS. There was a prolonged median time on treatment in Asian patients of 46.7 months. Median time on treatment was also longer in patients with Del19 versus L858R mutations (30.3 vs 19.1 months).

Median time on treatment was numerically longer in patients without baseline brain metastases versus those with brain metastases (28.4 vs 19.4 months). Of 183 patients with no brain metastases at baseline, 12 (6.6%) developed brain metastases while on afatinib. Of 21 patients with brain metastases at the start of afatinib therapy, eight (38%) were reported to have no brain metastases at the start of osimertinib therapy. Median time on treatment was also longer in patients with ECOG PS 0 or 1 versus ≥2 (31.3 vs 22.2 months).


Overall survival

At the time of analysis, 63 patients had died (31%). Therefore, overall survival (OS) analysis was limited to landmarks of 2 and 2.5 years, with maturity of 50% and 37%, respectively. In all patients in the study, the 2-year OS rate from start of afatinib treatment was 79% and the 2.5-year OS rate was 69%. In patients with ECOG PS 0 or 1, the 2-year OS rate was 84%.


Landmark OS at 2 years and 2.5 years in patients treated with sequential afatinib and osimertinib

GioTag study: overall survival with sequential afatinib and osimertinib

Mutational status after osimertinib discontinuation

Data on tumour mutation profile in terms of either EGFR sensitizing mutations and/or T790M were only available from 39 of the 106 patients who had discontinued osimertinib. Although mutation data after osimertinib discontinuation had been explicitly requested, no mutations other than common EGFR mutations (Del19/L858R) and/or T790M were reported.


This global, non-interventional study is the first study to evaluate outcomes for patients with EGFR mutation-positive NSCLC who received first-line afatinib followed by osimertinib as part of routine clinical practice. A sustained clinical benefit was observed with this treatment sequence. The broad patient population included patients who have not been well represented in randomised controlled trials, such as those with ECOG PS ≥2 (15% of patients in GioTag).

Molecular testing following progression on osimertinib was limited, which may reflect the lack of approved treatments in this setting.

Importantly, the clinical benefit was consistent across all patient subgroups, with particularly encouraging results in Asian patients and patients with Del19-positive disease. Patients with ECOG PS ≥2 and stable brain metastases also appeared to derive clinical benefit.

Overall, these data suggest that sequential afatinib and osimertinib is an effective treatment option in patients with EGFR mutation-positive NSCLC who subsequently acquire a T790M mutation.



Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT03370770 (Accessed: May 2018).


Hochmair MJ, et al. Future Oncol 2018; doi: 10.2217/fon-2018-0711 [Epub ahead of print].

Check full publication in the journal Future Oncology.

*Afatinib is approved in more than 80 markets including the EU, Japan, Taiwan, and Canada under the brand name GIOTRIF®, in the US under the brand name GILOTRIF® and in India under the brand name Xovoltib®; for the full list please see here. Registration conditions differ internationally; please refer to locally approved prescribing information.


© 2018 Boehringer Ingelheim International GmbH. All rights reserved.


Last updated: October 2018