Retrospective Multi-cohort Study of Frontline Afatinib Followed by 2nd Line Therapy Including Osimertinib, Chemotherapy or Other Therapy

Totality Outcome of Afatinib Sequential Treatment in Patients With EGFR Sensitizing Mutation-positive NSCLC in South Korea

The T790M mutation is highly sensitive to osimertinib, which is approved in this setting following failure of gefitinib, erlotinib or afatinib. In contrast to first- and second-generation EGFR TKIs, no predominant resistance mechanism to first-line osimertinib has been clearly defined yet. The most common mechanisms of resistance were c-MET amplification only for 15% of patients and the emergence of the EGFR C797S mutation in 7%, while > 60% of patients were still with no identifiable mechanisms of resistance. As a result, targeted treatment options following first-line osimertinib failure remain limited. Thus, interest on sequential administration of EGFR TKIs in patients with EGFR mutation-positive NSCLC has been growing. So, here in this study, we intend to investigate treatment outcome (TOT) along with the several treatment options starting from the first line EGFR TKI treatment to various second line treatments including 3rd generation TKI and chemotherapy and others.

Study Overview

• Status: Active, not recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: Gilotrif

• Study Type: Observational
• Enrollment (Actual): 737

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06591
    • Jin Hyoung Kang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

non-interventional, multi-center, multi-cohort

Description

Inclusion Criteria:

1. Age more than 18 years
2. Stage IIIB/IIIC/IV/IVA/IVB NSCLC patients treated with first-line afatinib for EGFR sensitizing mutations (Del19, L858R, G719X, S768I, or L861Q etc.)
3. Afatinib treatment was started 13 month prior to data collection date to reduce premature censoring of patients. Data cutoff date will be determined before data entry starts.

Exclusion Criteria:

1. Patients who received drug(s) other than afatinib (Giotrif®) as the first-line treatment
2. Patients who received drug(s) other than 3rd-generation EGFR TKI osimertinib as the second-line in "Cohort A'

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort A; T790M+ patients sequentially treated with osimertinib in cohort A	Drug: Gilotrif; This is non-interventional, multi-center, multi-cohort study based on existing data from EGFR sensitizing mutation-positive NSCLC patients treated with afatinib as the first-line treatment. Enrolled patients will be categorized into four cohorts (cohort A, B, C and D) according to the type of second line treatment with biopsy results before start of second line treatment.
Cohort B; T790M- patients treated with chemotherapy or other treatments in cohort B	Drug: Gilotrif; This is non-interventional, multi-center, multi-cohort study based on existing data from EGFR sensitizing mutation-positive NSCLC patients treated with afatinib as the first-line treatment. Enrolled patients will be categorized into four cohorts (cohort A, B, C and D) according to the type of second line treatment with biopsy results before start of second line treatment.
Cohort C; patients with unknown mutation status in cohort C	Drug: Gilotrif; This is non-interventional, multi-center, multi-cohort study based on existing data from EGFR sensitizing mutation-positive NSCLC patients treated with afatinib as the first-line treatment. Enrolled patients will be categorized into four cohorts (cohort A, B, C and D) according to the type of second line treatment with biopsy results before start of second line treatment.
Cohort D; Cohort D included patients who were still ongoing with afatinib.	Drug: Gilotrif; This is non-interventional, multi-center, multi-cohort study based on existing data from EGFR sensitizing mutation-positive NSCLC patients treated with afatinib as the first-line treatment. Enrolled patients will be categorized into four cohorts (cohort A, B, C and D) according to the type of second line treatment with biopsy results before start of second line treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total TOT	the time on treatment (total TOT) of EGFR M+ NSCLC patients treated with afatinib in the first-line (TOT-1) followed by second line treatments(TOT-2) including osimertinib, chemotherapy and other treatments.	Non-interventional study (NIS) based on the existing data from patients' medical records(2013-08-01 ~ 2029-04-30).

Secondary Outcome Measures

Outcome Measure	Time Frame
objective response rate (ORR-1 & ORR-2's)	Non-interventional study (NIS) based on the existing data from patients' medical records(2013-08-01 ~ 2029-04-30).
overall survival time	Non-interventional study (NIS) based on the existing data from patients' medical records(2013-08-01 ~ 2029-04-30).

Collaborators and Investigators

• Sponsor: Seoul St. Mary's Hospital
• Collaborators: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 24, 2020
• Primary Completion (ACTUAL): December 17, 2020
• Study Completion (ANTICIPATED): September 30, 2021

Study Registration Dates

• First Submitted: June 13, 2021
• First Submitted That Met QC Criteria: June 13, 2021
• First Posted (ACTUAL): June 18, 2021

Study Record Updates

• Last Update Posted (ACTUAL): June 18, 2021
• Last Update Submitted That Met QC Criteria: June 13, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: afatinib; T790
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Afatinib
• Other Study ID Numbers: TOAST

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No