Abstract 754: Treatment decision-making of rare ERBB2 (HER2) mutations in lung cancer; a role for multidisciplinary molecular tumor boards
Authors: Elst Arja ter , Hart Nils A. 't , Wekken Anthonie J. van der , Timens Wim , Hijmering-Kappelle Lucie B. , Hospers Geke A. , Jalving Hilde , Logt Elise M. van der , Kempen Leon C. van , Oosting Sjoukje F. , Groves Matthew R. , Hiltermann T Jeroen , Berg Anke van den , Groen Harry J. , Schuuring Ed 
Published: July 2017

Abstract
Introduction:
Breakthroughs in cancer research have resulted in mutation-specific targeted therapies (precision medicine). Most of these new drugs are only effective in patients with an actionable molecular profile. Thus, predictive molecular testing enables oncologists to select individual patients for the most appropriate (targeted) therapy and to reduce the burden of overtreatment. The number of clinically relevant predictive markers that are routinely analyzed is growing rapidly, resulting in the identification of rare mutations, mutations with unknown relevance and coexistence of two or more mutations in the same sample. Incorporating these into the optimal treatment for the individual patient can be complex.
Methods: A total of 2461 sequential tumor biopsies were analyzed at our institute using targeted next generation sequencing (Ion Torrent platform). 230 of these patients were discussed at a weekly Molecular Tumor Board (MTB) meeting. Cases involved 170 lung and 21 colorectal carcinomas, 24 melanomas, 1 GIST and a range of other malignancies with uncommon and rare mutations. The board is composed of pulmonologists, medical oncologists, pathologists and clinical scientists in molecular pathology. The goal of the MTB is to discuss the biological and clinical relevance of rare mutations or uncommon profiles and to suggest treatment options based on registered, off-label or trial-based drugs presently available in the Netherlands.
Results: In this abstract we report on four patients with an ERBB2 exon 20 mutation and 1 patient with ERBB2 amplification received anti-HER2 treatment after an MTB consensus decision. Two patients with an insertion in exon 20 of ERBB2: (c.2313_2324dup; p.(Y772_A775dup)) received first line therapy with afatinib and showed a partial response and stable disease respectively. One patient with a c.2524G&gt;A; p.(V842I) mutation received afatinib and showed stable disease for 3 months. A patient with another ERBB2 exon 20 insertion (c.2326_2327insTAT:p.(G776delinsVC)) received afatinib but had progressive disease within two months. One patient with an ERBB2 amplification by FISH and high (3+) HER2(ERBB2) expression, showed a partial response to trastuzumab. All patients had stage IV and would without genomic knowledge been treated with chemotherapy.
Conclusion: Lung cancer patients with sporadic ERBB2 mutations might benefit from targeted ERBB2 therapy. For an optimal treatment decision, patients with rare mutations in general, may benefit from discussion in a multidisciplinary molecular tumor board. In the future, both the considerations for targeted therapy as well as treatment response and toxicity should be registered in an open-access database and shared with other national and international Molecular Tumor Board initiatives to allow comparison with traditional treatments.
Citation Format: Arja ter Elst, Nils A. 't Hart, Anthonie J. van der Wekken, Wim Timens, Lucie B. Hijmering-Kappelle, Geke A. Hospers, Hilde Jalving, Elise M. van der Logt, Leon C. van Kempen, Sjoukje F. Oosting, Matthew R. Groves, T Jeroen Hiltermann, Anke van den Berg, Harry J. Groen, Ed Schuuring. Treatment decision-making of rare ERBB2 (HER2) mutations in lung cancer; a role for multidisciplinary molecular tumor boards [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 754. doi:10.1158/1538-7445.AM2017-754