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

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.^1,2

Trial CT.gov-Identifier: NCT03370770³

Patients

• EGFR mutation-positive advanced NSCLC¹
• Common EGFR mutations (Del19, L858R) at start of first-line treatment with afatinib¹
• Data were collected only in patients who had started osimertinib ≥10 months prior to data entry¹
• Patients with active brain metastases at the start of either therapy were excluded¹

N=204

Outcome measures

Primary outcome:

• Time on treatment, defined as the time from the first dose of afatinib to the time of the last dose of osimertinib or death²

Exploratory outcome:

• The overall survival (OS) analysis was exploratory and was defined as time from start of afatinib treatment to death²

Results

Patient characteristics

The patient population included a range of ethnicities with 120 (59%) Caucasian patients, 50 (25%) Asian patients and 18 (9%) African-American patients.^1-2 At the start of afatinib treatment, Eastern Cooperative Oncology Group performance status (ECOG PS) was 0/1 in 152 (75%) patients and ≥2 in 31 (15%) patients.²One hundred and forty-nine (73%) patients had a Del19 mutation, 53 (26%) had the L858R mutation and 21 (10%) had stable brain metastases.²

Overall survival

At the time of the final analysis (December 2019), median follow-up was 33.9 months.² Median OS was 37.6 months (90% confidence interval [CI]: 35.5–41.3) in the overall patient population, 44.8 months (90% CI: 37.0‒57.8) in Asian patients, and 41.6 months (90% CI: 36.9‒45.0) in patients with the Del19 EGFR mutation.² The 2-year OS rate from the start of afatinib treatment was 80% in the overall patient population, 90% in Asian patients, and 84% in patients with Del19-positive tumors.²

Clinical benefit of sequential afatinib and osimertinib was also observed across patient subgroups often excluded from clinical trials. Median OS was 31.0 months in patients with brain metastases, 36.9 months in patients aged ≥65 years, and 32.0 months in those with ECOG PS ≥2.²

Time on treatment

The median overall time on sequential afatinib and osimertinib treatment was 27.7 months (90% CI: 26.7–29.9) in the overall patient population, 37.1 months in Asian patients (90% CI: 28.1–40.3), and 30.0 months (90% CI: 27.6–31.9) in patients with Del19-positive tumors.²

Clinical benefit was also consistent in patients with poor prognostic characteristics: median time on treatment was 22.2 months in patients with brain metastases, 27.3 months in patients aged ≥65 years, and 22.2 months in those with ECOG PS  ≥2.²

Mutational status after osimertinib discontinuation

In the initial analysis (database lock: June 2018), data on tumor 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.¹ Although mutation data after osimertinib discontinuation had been explicitly requested, no mutations other than common EGFR mutations (Del19/L858R) and/or T790M were reported.¹

Study limitations

The main limitations of the GioTag study were its retrospective nature, the lack of a comparator arm, and the potential for selection bias by excluding patients who died after first-line afatinib treatment or under-representing patients who derived long-term benefit from first-line afatinib treatment.²

Conclusion

The final results of this international, observational study suggest that sequential afatinib followed by osimertinib can be a feasible and effective therapeutic strategy in real-world patients with EGFR mutation-positive NSCLC who develop T790M.²

Of note, median OS was over 3.5 years in Asian patients and patients with Del19-positive tumors, suggesting that sequential use of tyrosine kinase inhibitors could potentially allow these EGFR mutation-positive NSCLC patients to receive long-term, chemotherapy-free treatment.²

Importantly, the clinical benefit was consistent across patients with poor prognostic characteristics.² For example, patients with ECOG PS ≥2 and stable brain metastases also appeared to derive clinical benefit.²

Molecular testing following progression on osimertinib was limited, which may reflect the lack of approved treatments in this setting.¹

Overall, these data suggest that sequential afatinib followed by osimertinib can be a feasible and effective therapeutic strategy in real-world patients with EGFR mutation-positive NSCLC who develop T790M, particularly in Asian patients and patients with Del19-positive tumors.²