Real World Evidence

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Real-World Evidence with GILOTRIF in 2 separate studies2,3,16

Results are not intended for direct comparison with clinical trials because the real-world study was an observational trial with no comparator arm. Differences in study designs, patient populations, definitions of safety or efficacy outcomes, as well as data collection methods, make it difficult to compare real-world studies with clinical trials.

GioTag Study       RealGiDo Study

GioTag Study

Limitations: The main limitations of this study were its retrospective nature and potential for selection bias. The other main limitation of the study was a lack of a comparator arm, which limits interpretation of the results.

Study design2,16
Observational Study: Sequencing treatments with Afatinib and Osimertinib in patients with EGFR M+ mNSCLC

  • GioTag is a real-world, global, multicenter, noninterventional, observational study of 204 adult patients with EGFR M+ NSCLC (Del19/L858R)
  • The study used existing data from medical records or electronic health records (US only)
  • Patients had T790M-positive disease following first-line afatinib and had started on osimertinib treatment >10 months prior to data entry
  • The primary outcome was median time to treatment failure, also referred to as time on treatment (defined as the time from the first dose of afatinib to the time of the last dose of osimertinib or death)
  • The secondary outcome was the type and proportion of acquired resistance mechanisms after osimertinib treatment
  • Although OS was not a primary outcome of the study, it was measured and included as a part of the statistical analysis plan
  • For the interim analysis presented here, updated data were collected from 94 US patients with available electronic health records; final analysis, incorporating data from manual chart reviews of a further 29 patients, is anticipated in early 2020

EGFR=epidermal growth factor receptor; EGFR M+=epidermal growth factor receptor mutation positive; mNSCLC=metastatic non-small cell lung cancer; NSCLC=non-small cell lung cancer.

Interim Analysis of the Retrospective, Observational GioTag Study (2019)

Primary endpoint: Median time to treatment failure in overall population and EGFR M+ patients with Del19 mutations

Primary endpoint: Median time to treatment failure in overall population and EGFR M+ patients with Del19 mutations

Primary endpoint: Median overall survival in overall population and EGFR M+ patients with Del19 mutations

Primary endpoint: Median overall survival in overall population and EGFR M+ patients with Del19 mutations

  • In the LUX-Lung 3 study, GILOTRIF achieved nearly 3 years OS in patients with a Del19 mutation (33.3 months vs 21.1 months for pemetrexed-cisplatin; 95% CI: 0.36-0.79)1,4†
  • Up to 73% of patients with Del19 mutations may develop T790M mutations6,17
  • Patients with T790M mutations may be treated with osimertinib, the only approved T790M inhibitor, in second-line therapy18

Results are not intended for direct comparison with clinical trials because the real-world study was an observational trial with no comparator arm. Differences in study designs, patient populations, definitions of safety or efficacy outcomes, as well as data collection methods, make it difficult to compare real-world studies with clinical trials.

RealGiDo Study

Limitations: The main limitations of the study were its retrospective nature and potential for selection bias. Sites that had experience prescribing afatinib and managing adverse events regularly were included in the study, however, enrollment was capped at 15 patients per site.

Impact of afatinib dose modification on safety and effectiveness in patients with EGFR mutation-positive advanced NSCLC: results from a global real-world study (RealGiDo)3

Study design

  • A non-interventional, observational, global, retrospective study conducted in 228 patients enrolled from 13 countries treated with GILOTRIF tablets
  • Sites were included based on the commercial availability of afatinib prior to January 1, 2015 and the use of afatinib having been adopted as routine care for patients with EGFR mutations
  • Medical records of consecutive patients who met the following criteria were reviewed: aged ≥18 years with EGFR-mutated (del19/L858R), TKI-naïve, advanced NSCLC who were treated with first-line afatinib within the approved label and provided written informed consent where required
  • Inclusion was also restricted to patients with treatment initiation ≥6 months prior to enrollment
  • Patients were excluded if they had any contraindications to afatinib based on the label, had NSCLC with uncommon mutations, or had been treated within a clinical trial

Primary safety and efficacy outcomes

  • Percentage of patients with adverse drug reactions (ADRs) by severity
  • Time to treatment failure; synonymous with time on treatment
  • Time to progression

Secondary outcomes

  • Percentage of patients with a starting dose modification
  • Reasons for a starting dose modification

GILOTRIF starting dose3

Gilotrif Starting Dose

*Although assessed as part of a global study, not all are approved doses in the US.

Real-World Evidence reinforces that GILOTRIF Dose Adjustments may reduce the frequency and intensity of Adverse Reactions without compromising effectiveness3

Common adverse drug reactions (> 10% incidence) pre- and post-dose reduction within the first 6 months after starting on afatinib 40mg/day (N=91)3

Common adverse reactions

Median time to treatment failure & progression in RealGiDo3

Median time to treatment failure & progression

View Safety Information from LUX-Lung 3

NE=not evaluable.
Time to treatment failure is defined as the time from the first dose of afatinib to the last dose of afatinib. Time to progression is defined as the time from the first dose of afatinib to the earliest occurrence of documented progression or death.

These results suggest afatinib was an effective 1st-line treatment for patients with EGFR M+ mNSCLC and that tailoring the afatinib dose based on individual patient characteristics can reduce the frequency and intensity of ADRs without compromising effectiveness3

Results are not intended for direct comparison with clinical trials because the real-world study was an observational trial with no comparator arm. Differences in study designs, patient populations, definitions of safety or efficacy outcomes, as well as data collection methods, make it difficult to compare real-world studies with clinical trials.

Read about Dose Modifications for Adverse Reactions

References: 1. GILOTRIF [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. 2. Hochmair MJ, Morabito A, Hao D, et al. Sequential treatment with afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: an observational study [published online October 19, 2018]. Future Oncol. doi:10.2217/fon-2018-0711 3. Halmos B, Tan EH, Soo Ra, et al. Impact of afatinib dose modification on safety and effectiveness in patients with EGFR mutation-positive advanced NSCLC: results from a global real-world study (RealGido). Lung Cancer. 2019;127:103-11. 4. Yang JCH, Wu YL, Schuler M, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16(2):141-151. 5. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327-3334. 6. Ke EE, Zhou Q, Zhang QY, et al. A higher proportion of the EGFR T790M mutation may contribute to the better survival of patients with exon 19 deletions compared with those with L858R. J Thorac Oncol. 2017;12(9):1368-1375. 7. Data on file. Boehringer Ingelheim. CTR. 8. Lee CK, Wu YL, Ding PN, et al. Impact of specific epidermal growth factor receptor (EGFR) mutations and clinical characteristics on outcomes after treatment with EGFR tyrosine kinase inhibitors versus chemotherapy in EGFR-mutant lung cancer: a meta-analysis. J Clin Oncol. 2015;33(17):1958-1965. 9. Yang JC, Sequist LV, Geater SL, et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX- Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015;16(7):830-838. 10. Yang JCH, Wu JYS, Hsia TC, et al. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012;13:539-548. 11. Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15(2):213-222. 12. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: non-small cell lung cancer, version 5. 2018. 13. Soria JC, Felip E, Cobo M, et al. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015;16(8):897 907. 14. Yang JCH, Sequist LV, Zhou C, et al. Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials. Ann Oncol. 2016;27(11):2103-2110.  15. U.S. Food & Drug Administration (FDA). FDA broadens afatinib indication to previously untreated, metastatic NSCLC with other non-resistant EGFR mutations (press release). https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm592558.htm. Accessed 3.13.2019.

Indications and usage

  • GILOTRIF (afatinib) tablets is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test.

    Limitation of Use: Safety and efficacy of GILOTRIF have not been established in patients whose tumors have resistant EGFR mutations.

  • GILOTRIF is indicated for the treatment of patients with metastatic squamous NSCLC progressing after platinum-based chemotherapy.

Adverse Reactions; LUX-Lung 3