Observational Study of Afatinib 30 mg Daily

An Observational Study of Afatinib 30 mg Daily in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) Harbouring Common EGFR Mutations Treated With Afatinib

Afatinib, a first-in-class irreversible ErbB family blocker, is a 1st line treatment option for patients with advanced stage NSCLC harbouring sensitizing EGFR mutations. In randomized 1st line studies of afatinib at a standard dose of 40 mg daily versus standard of care, 28-53% of patients required a dose reduction due to adverse events (AE) induced by afatinib. The most common AEs are cutaneous and gastrointestinal (diarrhoea, dysphagia, and mucositis). Prevalence of diarrhoea in patients receiving 40 mg of afatinib, in 1st line phase II and III studies is as high as 90.0% (all grades of diarrhoea) and 14.4% (grade 3-4 diarrhoea). Another important gastrointestinal AE is mucositis, which presents in 51.9%-64.4% of patients treated with afatinib, with only 4.4%-8.3% of the cases being grade 3-4. Dose reduction tended to occur in patients who had higher initial afatinib plasma concentrations and led to decreases in the incidence and severity of afatinib-related AEs without affecting therapeutic efficacy. The incidence of gastrointestinal AEs could be decreased >50% with proper afatinib dose reduction.

The effect of 1st line afatinib 30 mg daily in patients with EGFR mutation-positive NSCLC is unknown. We hypothesize that, in patients with EGFR mutation-positive NSCLC, 1st line afatinib treatment at 30 mg daily is tolerable with less gastrointestinal AEs and with a similar efficacy to standard dose afatinib.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer; Epidermal Growth Factor Receptor Mutation
• Intervention / Treatment: Drug: Afatinib

Detailed Description

This is a multi-country, multi-centre, study designed to collect clinical data and to evaluate efficacy and safety of patients treated with afatinib 30 mg at the Investigator's discretion.

All entered patients (i.e., patients that have been treated with the defined medication) will receive continuous treatment of afatinib in the absence of disease progression or meeting any other withdrawal criteria. All patients will visit Investigator at regular intervals for assessment of efficacy and safety as outlined in the Flow Chart for the first 7 cycles treatment. The Investigator will assess the patient at each visit. Tumour response and progression will be assessed using RECIST 1.1 at the Investigator site.

• Study Type: Observational
• Enrollment (Estimated): 69

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • Recruiting
    • Nationa University Hospital
    • Contact: Ross Soo, MBBS; Phone Number: +65 6908 2222; Email: Ross_Soo@nuhs.edu.sg
    • Principal Investigator: Ross Soo, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients who has taken 30 mg Afatinib as initial dose and still on treatment for less than 28 days

Description

Inclusion Criteria:

1. Age ≥18 years.
2. ECOG performance status 0-1.
3. Pathologically confirmed diagnosis of Stage IIIB/IV adenocarcinoma of the lung.
4. Have been commenced on first line afatinib 30 mg within 4 weeks of study enrolment.
5. Documented EGFR mutation(s)-positive NSCLC (common mutations: Del19 and L858R) from tumour biopsy material. Results of EGFR mutation test must be available before taking Afatinib.
6. A CT thorax/ abdomen within 4 weeks of study enrolment with at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
7. No brain metastases (confirmed by a CT or MRI brain performed within 4 weeks of study enrolment)

8. Documented adequate organ function before taking Afatinib:

   • Absolute neutrophil count (ANC) ≥1500/mm3. (ANC >1000/mm3 may be considered in special circumstances such as benign cyclical neutropenia as judged by the Investigator and in discussion with the sponsor-Investigator).
   • Platelet count ≥75,000/mm3.
   • Estimated creatinine clearance using Cockcroft Gault calculation of at least 45 ml/min.
   • Total Bilirubin ≤1.5 times upper limit of (institutional/central) normal (Patients with Gilbert's syndrome total bilirubin must be ≤4 times institutional upper limit of normal).
   • Aspartate amino transferase (AST) or alanine amino transferase (ALT) ≤3 times the upper limit of (institutional/central) normal (ULN) (if related to liver metastases ≤5 times ULN).
9. Archived tissue sample is available.
10. Written informed consent per regulations.

Exclusion Criteria:

1. Prior chemotherapy for Stage IIIB/IV adenocarcinoma of the lung. Neo-/adjuvant chemotherapy, CT-RT or RT is permitted if it has been elapsed for =12 months prior to disease progression.
2. Prior treatment with EGFR targeting small molecules or antibodies.
3. Major surgery within 4 weeks of study treatment.
4. Brain metastases.
5. Meningeal carcinomatosis.
6. Known pre-existing interstitial lung disease (ILD).

7. Patients with a significant disease other than lung cancer; a significant disease is defined as a disease which, in the opinion of the investigator, may:

   • put the patient at risk because of participation in the study
   • influence the results of the study
   • cause concern regarding the patient's ability to participate in the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Afatinib 30 mg daily; Oral afatinib 30 mg tablet once daily, continuously	Drug: Afatinib; Continuous treatment of afatinib 30mg tablet once daily in the absence of disease progression or unacceptable treatment-related toxicity, Investigator decision or patient decision to discontinue study treatment.; Other Names: Giotrif

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival rate	To assess the effect of afatinib 30 mg daily at the Investigator's discretion on progression-free survival rate (PFSR) at month 6.	6 months

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Collaborators: Boehringer Ingelheim

Publications and helpful links

General Publications

• Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1.
• Tan DS, Yom SS, Tsao MS, Pass HI, Kelly K, Peled N, Yung RC, Wistuba II, Yatabe Y, Unger M, Mack PC, Wynes MW, Mitsudomi T, Weder W, Yankelevitz D, Herbst RS, Gandara DR, Carbone DP, Bunn PA Jr, Mok TS, Hirsch FR. The International Association for the Study of Lung Cancer Consensus Statement on Optimizing Management of EGFR Mutation-Positive Non-Small Cell Lung Cancer: Status in 2016. J Thorac Oncol. 2016 Jul;11(7):946-63. doi: 10.1016/j.jtho.2016.05.008. Epub 2016 May 23.
• Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. 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 Feb;16(2):141-51. doi: 10.1016/S1470-2045(14)71173-8. Epub 2015 Jan 12.

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2022
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: May 26, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): June 1, 2021

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 15, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: afatinib; EGFR mutation-positive NSCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Afatinib
• Other Study ID Numbers: 1200.0303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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