GioTag real-world evidence study

50–70% of patients treated with afatinib 1st-line may develop a T790M resistance mutation.1–3 

T790M mutations have been found to be even more prevalent in Del19 vs. L858R tumours, occurring in approximately 75% or patients.4,5

Osimertinib is effective against T790M positive NSCLC, and is approved for use in this population.6 Osimertinib is also approved for 1st-line treatment of EGFR NSCLC, but resistance mechanisms are heterogeneous, poorly understood and not treatable with approved target therapies, leaving chemotherapy as the likely treatment option following resistance development.7

In previous studies, no known resistance mechanism could be identified in over 60% of cases where osimertinib was used for 1st-line treatment.8-9

The GioTag study was a real-world retrospective study which focused on the sequential treatment of afatinib followed by osimertinib in EGFR M+ NSCLC patients with T790M acquired resistance in order to assess the effectiveness of this sequential treatment approach.4

Learn more about how real-world evidence can complement clinical trial data.

Read the full GioTag study publication.


Study Design

A real-world, non-interventional, global study of sequential therapy with afatinib in 1st-line followed by osimertinib for acquired T790M in 204 patients with EGFR M+ positive NSCLC (Del19/L858R). The study used existing data from medical records or electronic health records (US only). The primary outcome was TTF, defined from the start of the 1st-line treatment with afatinib until the end of the 2nd-line treatment.4

 

Results from the GioTag study may be impacted by limitations of the study design:4

  • Patients who died on 1st-line afatinib were excluded from the study which potentially introduced an immortal time bias
  • Due to the study timelines and dates of drug approvals, patients who derived long-term benefit from 1st-line afatinib had little chance to be enrolled in the study and may have therefore been under-represented

TTF (afatinib followed by osimertinib)

Afatinib followed by osimertinib secured a median TTF of 27.6 months in clinical practice4

GioTag study: TTF in patients receiving afatinib followed by osimertinib4

GioTag study results: chart showing TTF in patients receiving afatinib followed by osimertinib

Adapted from Hochmair MJ, et al. 2018.4

For patients with a Del19 mutation the benefit of the sequence of afatinib followed by osimertinib was pronounced4

GioTag study: TTF by EGFR mutational subgroup4

GioTag study results: chart showing TTF by activation mutation type

Adapted from Hochmair MJ, et al. 2018.4

For patients of Asian ethnicity, afatinib treatment followed by osimertinib secured a median time on oral targeted therapy of 46.7 months in clinical practice4

GioTag study: TTF by patient ethnicity4

GioTag study results: chart showing TTF by patient ethnicity

Adapted from Hochmair MJ, et al. 2018.4


OS

At 2 years, 79% of patients treated with the sequence of afatinib followed by osimertinib were still alive4

GioTag study: OS in patients with mutations4

GioTag study results: chart showing OS in patients with mutations

Adapted from Hochmair MJ, et al. 2018.4

aMaturity was 50%. bMaturity was 37%. 

Median OS was not calculated as the study had only reach 31% maturity at the time of the analysis.4


CI=confidence interval, ECOG PS = eastern cooperative oncology group performance status, EGFR M+=epidermal growth factor receptor mutation positive, OS=overall survival, RCT=randomised clinical trial, TTF=time-to-treatment failure


References

1
Hochmair M et al. Poster #73255 presented at: International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer; Yokohama, Japan; 15-18 October 2017.
2
Yang JC, et al. J Clin Oncol 2017;35(12):1288–1296.
3
Wu SG, et al. Oncotarget 2016; 7:12404–12413.
4
Hochmair MJ, et al. Future Oncol 2018; doi:10.2217/fon-2018-071.
5
Jenkins S, et al. J Thorac Oncol 2017;12(8):1247–1256.
6
Ramalingam SS, et al. Mechanisms of acquired resistance to first-line osimertinib: preliminary data from the phase III FLAURA study. ESMO congress 2018.
7
Rudin CM. Discussion: Acquired Resistance to Osimertinib. ESMO congress 2018.
8
Osimertinib Summary of Product Characteristics, 2018.
9
Girard N. Future Oncol 2018;14(11):1117–1132.