A Phase 2 Trial of Afatinib in Patients with Solid Tumors that Harbor Genomic Aberrations in the HER family: The MOBILITY3 Basket Study.

Abstract

BACKGROUND:

Epidermal growth factor receptor (EGFR)- and human epidermal growth factor receptor (HER)2-targeted therapies are approved for the treatment of breast, gastric/gastrointestinal junction (GEJ), and non-small cell lung cancer (NSCLC) with specific molecular aberrations affecting HER family members. Over 10 % of other cancers harbor genomic aberrations affecting HER family members, but their role remains undefined.

OBJECTIVE:

The MOBILITY3 trial evaluated the antitumor activity of afatinib, an oral pan-HER tyrosine kinase inhibitor (TKI) in HER-aberrant tumors outside of the licensed indications.

PATIENTS AND METHODS:

In this single-center basket trial, patients with advanced solid tumors that harbor mutations and/or amplifications of any of the HER family members (EGFR, ERBB2, ERBB3, ERBB4) were enrolled. The EGFR-mutated NSCLC and HER2-positive breast cancers were excluded. Participants were treated with oral afatinib 40 mg daily until disease progression or unacceptable toxicity. Objective response rate (ORR) and progression-free survival (PFS) were primary and secondary endpoints, respectively.

RESULTS:

The study enrolled 12 patients with 6 tumor types (NSCLC, sarcoma, salivary gland, gastric/GEJ, breast and pancreatic cancer). Objective response rate was 8 % (95 % CI 0.2-38%) and median PFS was 11.4 weeks (95% CI 4.6-33.3 weeks). All 3 patients with salivary gland cancers and 1 patient with ERBB2-mutant NSCLC had clinical benefit (stable disease or partial response lasting > 24 weeks). Due to slow accrual and a lower-than-expected response rate, trial recruitment was terminated before the target of 30 patients were enrolled.

CONCLUSIONS:

In the MOBILITY3 study (NCT02506517), afatinib demonstrated modest activity in tumors that possess EGFR and ERBB2 aberrations. Clinical benefit seen in all 3 salivary gland cancers supports the growing evidence for the utility of HER-targeted therapies in the treatment of this specific tumor type.

• Authors: Abdulazeez Salawu, Aaron R Hansen, Anna Spreafico, Esmail Al-Ezzi, Sheila Webster, Philippe L Bedard, Jeffrey Doi, Lisa Wang, Lillian L Siu, Albiruni R Abdul Razak
• Journal: Targeted oncology (Target Oncol) Vol. 17 Issue 3 Pg. 271-281 (05 2022) ISSN: 1776-260X [Electronic] France
• PMID: 35635640 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Chemical References

• Protein Kinase Inhibitors
• Afatinib

Topics

• Afatinib (pharmacology, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Genomics
• Humans
• Lung Neoplasms (drug therapy)
• Mutation
• Protein Kinase Inhibitors (pharmacology, therapeutic use)