Sequential afatinib and osimertinib in patients with EGFR mutation-positive NSCLC and acquired T790M: A global non-interventional study (UpSwinG).

Abstract

BACKGROUND:

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard of care for EGFR mutation-positive non-small cell lung cancer (NSCLC). However, optimal sequence of treatment has yet to be defined. Overall survival (OS) is influenced by the availability/use of subsequent therapy after first-line treatment. Emergence of T790M is the main mechanism of resistance to afatinib and second-line osimertinib could be a treatment option in this instance.

METHODS:

In this non-interventional, global study (NCT04179890), existing medical/electronic records were identified for consecutive EGFR TKI-naïve patients with EGFR mutation-positive NSCLC (Del19 or L858R) treated with first-line afatinib and second-line osimertinib in regular clinical practice (n = 191; all T790M-positive). The primary objective was time to treatment failure (TTF). Key secondary objectives were OS and objective response rate (ORR).

RESULTS:

At the start of afatinib treatment, median age (range) was 62 years (34-88). Fifty-five percent of patients were female and 67% were Asian. ECOG PS (0/1/≥2) was 31%/57%/12%. Fourteen percent of patients had brain metastases. At the start of osimertinib treatment, ECOG PS (0/1/≥2) was 25%/61%/14% and 14% had brain metastases (rising to 29% at the end of osimertinib treatment). The source of biopsy material (solid/liquid) was 86%/3% at the start of afatinib and 54%/33% at start of osimertinib. Mutations were mainly detected with PCR methods. Overall, median TTF was 27.7 months (95% CI: 24.0-30.2) and median OS was 36.5 months (95% CI: 32.9-41.8). ORR with afatinib and osimertinib was 74% and 45%. TTF, OS and ORR were generally consistent across subgroups.

CONCLUSION:

Sequential afatinib and osimertinib demonstrated encouraging activity in patients with EGFR mutation-positive NSCLC and acquired T790M. Activity was observed across all subgroups, including patients with poor ECOG PS or brain metastases. ECOG PS and incidence of brain metastases remained stable prior to, and after, afatinib treatment.

• Authors: Sanjay Popat, Hyun Ae Jung, Shin Yup Lee, Maximilian J Hochmair, Seung Hyeun Lee, Carles Escriu, Min Ki Lee, Maria R Migliorino, Yong Chul Lee, Nicolas Girard, Hasan Daoud, Angela Märten, Satoru Miura
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 162 Pg. 9-15 (12 2021) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 34649106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Acrylamides
• Aniline Compounds
• Protein Kinase Inhibitors
• osimertinib
• Afatinib
• EGFR protein, human
• ErbB Receptors

Topics

• Acrylamides
• Afatinib (therapeutic use)
• Aniline Compounds
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• ErbB Receptors (genetics)
• Female
• Humans
• Lung Neoplasms (drug therapy, genetics)
• Middle Aged
• Mutation
• Protein Kinase Inhibitors (therapeutic use)