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

Verlingue, Loïc; Massard, Christophe; Hollebecque, Antoine; Álvarez, E. Castañón; Postel-Vinay, Sophie; Angevin, Eric; Jp, Armand; Aspeslagh, Sandrine; Varga, Andréa; Ratislav, B.; Gazzah, Anas; Michot, Jean‐Marie; Lacroix, Ludovic; Baère, Thierry De; Marabelle, Aurélien; Soria, J-C.

doi:10.1093/annonc/mdw363.70

Cited by 4 publications

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“…These observations support the need to tailor the treatment of patients to the type of alterations found in the ERBB2 gene. Moreover, recent evidences suggest that HER2 inhibitors may be efficient in broader molecular alterations such as ERBB3 [ 25 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of histology-agnostic and molecularly-driven HER2 inhibitors for refractory cancers

et al. 2018

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A targeted therapy is recommended in case of ERBB2 alteration for breast and gastric carcinomas, but miscellaneous other tumor types are ERBB2-altered at low prevalence. Broadening the administration of HER2 inhibitors across tumor types and genomic alterations could benefit to patients with refractory metastatic tumors.Targeted next-generation-sequencing (tNGS) and comparative genomic hybridization array (CGH) have been performed on fresh tumor biopsies of patients included in the MOSCATO-01 and ongoing MOSCATO-02 trials to administrate HER2 inhibitors in case of ERBB2 pathogenic mutation of amplification.Between December 2011 and January 2017 a molecular analysis was performed for 934 patients (759 CGH and 912 tNGS). A novel ERBB2 alteration has been found in 4.7% (n = 44/934), including 1.5% (n = 14/912) ERBB2 mutations, and 4% (n = 30/759) ERBB2 amplifications.A matched HER2 inhibitor was administrated to 70% (31/44) of patients and consisted in trastuzumab plus chemotherapy for 90% of them (28/31). On the 31 evaluable patients, 1 complete response (CR), 10 partial response (PR) and 2 stable disease (SD) >24 weeks were observed accounting for a clinical benefit rate (CBR) of 42% (n = 13/31, 95% CI 25–61%). Besides breast and oesogastric carcinomas, 19 patients affected by 8 different tumor types had a CBR of 25% for ERBB2 mutations (n = 2/8, 95% CI 3%–65%, with 2 PR) and 64% for ERBB2 amplifications (n = 7/11, 95% CI 31%–89%; with 1 CR, 4 PR, 2 SD).ERBB2 genomic alterations were diffuse across metastatic tumor types and signs of efficacy emerged for HER2 targeted treatments, especially in case of ERBB2 amplifications or a p.S310Y ERBB2 mutation.

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Section: Discussionmentioning

confidence: 99%

Efficacy of histology-agnostic and molecularly-driven HER2 inhibitors for refractory cancers

et al. 2018

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Section: Discussionmentioning

confidence: 99%

“…33 Additionally, two metastatic urothelial cancers with ERBB3 V104M and G284R mutations achieved 6.3 months and 7 months of PFS, respectively, after treatment with the inhibitor afatinib (Table 1). 32 Pyrotinib is an oral, irreversible pan-ErbB inhibitor capable of blocking EGFR/HER1, HER2, and HER4 activities. 28 A Phase II study showed that pyrotinib was effective in treating HER2-positive breast cancer, with a superior response to lapatinib.…”

Section: Dovepressmentioning

confidence: 99%

Gastric Cancer Harboring an ERBB3 Mutation Treated with a Pyrotinib–Irinotecan Combo: A Case Study

Ding¹,

Chen²,

Li³

et al. 2021

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Gastric cancer is common, especially in East Asian countries, and is associated with high recurrence and mortality rates. Currently, there is no standard third-line treatment for metastatic gastric cancer. In this report, we present the case of a 69-year-old man with advanced gastric cancer, whose tumor was negative for human epidermal growth factor receptor 2 (HER2) according to immunohistochemical analysis. Next-generation sequencing performed on paraffin sections of the postoperative tumor samples indicated the presence of the ERBB3 V104L mutation. The patient received irinotecan plus pyrotinib as a third-line therapy and achieved a progression-free survival of 7.6 months with a high quality of life. Therefore, the combined administration of irinotecan and pyrotinib may improve the clinical condition of patients with gastric cancer harboring an ERBB3 mutation. Moreover, ERBB3 could be a potential therapeutic target for gastric cancer.

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“…Authors reported two PRs. Out of six patients with SD, the BC patient had 504 days on capecitabine þlapatinib association, and the lung squamous cell carcinoma patient had 420 days on afatinib [35]. On the contrary, no drug's activity was observed in the ERRB3-mutant cohort in the SUMMIT trial (n ¼ 16) [30].…”

Section: Tier IIImentioning

confidence: 99%

Genomic alterations in breast cancer: level of evidence for actionability according to ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)

et al. 2019

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Better knowledge of the tumor genomic landscapes has helped to develop more effective targeted drugs. However, there is no tool to interpret targetability of genomic alterations assessed by next-generation sequencing in the context of clinical practice. Our aim is to rank the level of evidence of individual recurrent genomic alterations observed in breast cancer based on the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) in order to help the clinicians to prioritize treatment. Analyses of databases suggested that there are around 40 recurrent driver alterations in breast cancer. ERBB2 amplification, germline BRCA1/2 mutations, PIK3CA mutations were classified tier of evidence IA based on large randomized trials showing antitumor activity of targeted therapies in patients presenting the alterations. NTRK fusions and microsatellite instability (MSI) were ranked IC. ESR1 mutations and PTEN loss were ranked tier IIA, and ERBB2 mutations and AKT1 mutations tier IIB. Somatic BRCA 1/2 mutations, MDM2 amplifications and ERBB 3 mutations were ranked tier III. Seventeen genes were ranked tier IV based on preclinical evidence. Finally, FGFR1 and CCND1 were ranked tier X alterations because previous studies have shown lack of actionability.

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

Cited by 4 publications

References 0 publications

Efficacy of histology-agnostic and molecularly-driven HER2 inhibitors for refractory cancers

Efficacy of histology-agnostic and molecularly-driven HER2 inhibitors for refractory cancers

Gastric Cancer Harboring an ERBB3 Mutation Treated with a Pyrotinib–Irinotecan Combo: A Case Study

Genomic alterations in breast cancer: level of evidence for actionability according to ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)

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