122P - Clinical efficacy of HER3 partners' inhibitors in ERBB3 mutated cancer patients

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Loic Verlingue
Citation Annals of Oncology (2016) 27 (6): 15-42. 10.1093/annonc/mdw363
Authors L. Verlingue1, C. Massard1, A. Hollebecque1, E. Castanon Alvarez1, S. Postel-Vinay1, E. Angevin1, J. Armand1, S. Aspeslagh1, A. Varga1, B. Ratislav1, A. Gazzah1, J. Michot1, L. Lacroix2, T. De Baere3, A. Marabelle1, J. Soria4
  • 1Drug Development Department (ditep), Institut Gustave Roussy, 94800 - Villejuif/FR
  • 2Laboratoire De Recherche Translationnelle Et Centre De Ressources Biologiques, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 3Interventional Radiology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 4Drug Development Department (ditep), Gustave Roussy, University Paris-Saclay, 94805 - villejuif/FR



Mutations affecting ERBB3 are rare but diffuse across cancer types. Besides the case report of an effective treatment by HER2 double blockade in an ERBB3 mutated breast cancer patient, the clinical efficacy of treatments targeting ERBB3 mutations remain largely unknown1. The objective of our study was to evaluate the efficacy of approved HER3 partners' inhibitors in the ERBB3 mutant population.


We retrospectively evaluated the clinical efficacy of HER3 partner's inhibitor in ERBB3 mutant tumors. ERBB3 mutations were detected using Targeted Gene Panel Sequencing in patients enrolled in our molecular screening program (MOSCATO 01).


Mutations in ERBB3 were observed in less than 2% of the cases (12 patients) in various tumor types: head and neck SCC (2), biliary tract carcinoma (2), a rectal neuroendocrine tumor, an urothelial bladder carcinoma, a clear cell adenocarcinoma of the cervix, a carcinoma of unknown primary, a lung SCC, an invasive lobular breast carcinoma and a pterygoid sarcoma. Overall, 7 patients received HER3 partners' inhibitors (trastuzumab and/or lapatinib or afatinib), 4 patients received other molecularly targeted agents (mTOR, PI3K or NOTCH inhibitors) and one failed being treated. We observed 1 partial response (PR) with the association of trastuzumab + lapatinib for a biliary tract carcinoma patient and 1 PR for a HNSCC patient with torisel. Out of 6 patients with stable disease (SD), the breast cancer patient had 504 days on xeloda + lapatinib association, and the lung SCC patient had 420 days on afatinib. When the mutation was located in the tyrosine kinase domain (TKD), patients were highly sensitive to HER3 partners' inhibitors, compared to mutations out of the TKD (hazard ratio for PFS = 6.63, p value = 0.01). Conversely, poor treatment efficacy was associated with the following parameters: mutations in the extracellular domain, >2 coexisting driver alterations, and > 1 previous systemic treatment line.


This preliminary data supports the role of ERBB3 as an oncogenic driver. Larger cohorts of patients with ERBB3 mutations will be required to further identify and validate characteristics that drive sensitivity to HER3 partners' inhibitors.

Clinical trial identification

Legal entity responsible for the study

Gustave Roussy Cancer Campus


Gustave Roussy Cancer Campus


All authors have declared no conflicts of interest.