201P - Afatinib for EGFR, HER2 or HER3 mutated solid tumors: A phase II Belgian precision study

Background

The Belgian Precision initiative aims to implement tumor-agnostic NGS in advanced cancer patients (pts) and enhance access to genotype-matching drugs. The current study aimed to investigate the efficacy of afatinib in advanced pre-treated solid cancers with an EGFR (excluding non-small cell lung cancer (NSCLC)), HER2 or HER3 mutation.

Methods

Open-label phase 2 study including 3 cohorts for previously treated advanced cancers: EGFR, HER2 and HER3 mutated. The primary endpoint for each cohort was objective response rate (ORR). Response assessment was performed every 8 weeks. For each cohort, a Simon two-stage design was used. The null hypothesis that the true ORR is 10%, was tested against a one-sided alternative that the true ORR is 30%. If two or more ORR were observed in the first ten pts, 19 additional pts were included (type I error 5% and power 80%) Secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety.

Results

A total of 45 pts were included in the trial with median age 62 years. The EGFR cohort comprised 7 pts: 2 pancreas, 1 head and neck, 1 breast, 1 endocrine tumor, 1 cervix and 1 kidney. The HER2 cohort comprised 30 pts: 11 NSCLC, 8 breast, 3 cervix, 2 colorectal, 2 head and neck, 1 bladder, 1 kidney, 1 liver and 1 pancreas. The HER3 cohort comprised 8 pts: 2 breast, 2 pancreas, 1 colorectal, 1 head and neck, 1 esophagus and 1 stomach. ORR and DCR were respectively 28.6% and 42.9% in the EGFR cohort, 3% and 49% in the HER2 cohort and 0% and 62.5% in the HER3 cohort. Partial responses were observed in a HER2-mutated NSCLC (1/11) with a DOR of 8.5 months, an EGFR-mutated breast cancer (1/1) with a DOR of 6.6 months and an EGFR-mutated pancreas cancer (1/2) with a DOR of 15.4 months. PFS and OS data will be presented at the meeting Safety data were consistent with the known safety profile of afatinib.

Conclusions

Although three pts demonstrated a clinical meaningful benefit, afatinib did not result in a significant ORR improvement in the HER2 cohort, which completed accrual. Recruitment was hampered by a lack of systematic agnostic NGS sequencing and the COVID epidemic. Broader and more systematic agnostic NGS would enable further exploration of HER inhibition in solid tumors

Clinical trial identification

EudraCT 2016-003411-34 Protocol No: 120.264 release date 26/09/2016.

Editorial acknowledgement

Legal entity responsible for the study

Department Medical Oncology, UZ Brussel.

Funding

Kom op tegen kanker.

Disclosure

L. Decoster: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, MSD; Financial Interests, Institutional, Invited Speaker: BMS, MSD, Roche, Servier, Sanofi; Financial Interests, Institutional, Research Grant, conduct of academic trial: Boehringer Ingelheim; Non-Financial Interests, Leadership Role, member of board: European Cancer Organisation; Non-Financial Interests, Leadership Role, Board member: International Society of Geriatric Oncology (SIOG). P.G. Aftimos: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius, Deloitte, Menarini, Gilead, Novartis, Eisai, Lilly; Financial Interests, Personal, Invited Speaker: Synthon, Amgen; Financial Interests, Institutional, Research Grant: Roche. S. Rottey: Financial Interests, Institutional, Advisory Board: Pfizer, Merck, Roche, Ipsen, BMS; Financial Interests, Institutional, Invited Speaker: Ipsen, BMS, Astellas; Financial Interests, Institutional, Research Grant: MSD, Roche, BMS; Non-Financial Interests, Principal Investigator, It is my main task in the hospital to attract and perform clinical trials in oncology phase I-III: all companies performing clinical trials in oncology in Europe. H. Prenen: Financial Interests, Institutional, Advisory Board: Amgen, Roche, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Bayer, Ipsen, Sanofi. J. Canon: Financial Interests, Institutional, Research Grant: Roche. J. De Grève: Financial Interests, Institutional, Invited Speaker: Roche. All other authors have declared no conflicts of interest.