Abstract 57P
Background
Phyllodes tumours (PT) are rare fibroepithelial neoplasms accounting for less than 1% of all breast tumours in Western countries and up to 7% amongst Asian populations. Currently, no established standard therapy exists for malignant PT, an aggressive chemoresistant subtype with high metastatic potential. We hypothesized that patient-derived xenograft (PDX) and cell line models created in “real-time” may identify effective therapies to mirror a patient’s treatment trajectory.
Methods
Malignant PT from a chest wall mass was subcutaneously inoculated onto female NSG™ mice with serial transplantation to establish a PDX and cell line model (designated MPT-S1). In vitro cell viability and cell cycle analyses were performed following drug exposures.
Results
The affected patient was diagnosed with metastatic malignant PT affecting the chest wall and lungs. Histology of the chest wall mass showed a high grade malignant tumour composed of markedly pleomorphic spindle cells, interspersed with osteoclast-like multinucleated giant cells. On immunohistochemistry, tumour cells were positive for p63, negative for MNF116 and showed high proliferative index on Ki-67. Whole exome sequencing followed by Sanger sequencing confirmed mutations in TP53, PRB, MED12 and KMT2D. Immunohistochemistry and genomic profiles of the patient’s tumour, PDX, and cell line were consistent. Interestingly, despite primary resistance to conventional chemotherapies including doxorubicin, gemcitabine and docetaxel, the patient achieved partial response to off-label treatment with pazopanib, a multi-targeted receptor tyrosine kinase inhibitor (TKI). Correspondingly, drug susceptibility testing in vitro showed that pazopanib reduced cell viability in a dose-dependent manner (IC50 6.37 μM), accompanied by induction of S-phase arrest and apoptosis. Other TKIs including sorafenib, sunitinib and axitinib elicited similar effects (all IC50 <5 μM).
Conclusions
We established MPT-S1, a new PDX and cell line model of malignant PT, and provided initial evidence for the clinical utility of such models for identifying therapeutic vulnerabilities of rare cancers in real-time.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
SingHealth, Duke-NUS.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
393P - Clinical characteristics and prognosis of patients with pulmonary mucoepidermoid carcinoma: A SEER-based analysis
Presenter: Lingxiao Qiu
Session: e-Poster Display Session
394P - Apatinib plus etoposide capsules as third-line or further-line treatment for extensive stage small cell lung cancer patients: A multicenter, single arm, phase II clinical trial
Presenter: Zhen He
Session: e-Poster Display Session
395P - Afatinib in Asian and non-Asian patients (pts) with EGFR mutation positive (EGFRm+) NSCLC harboring major uncommon mutations
Presenter: James Chih-Hsin Yang
Session: e-Poster Display Session
396P - Efficacy and safety of S-1 in elderly patients with advanced non-small cell lung cancer previously treated with platinum-based chemotherapy: A subgroup analysis of the EAST-LC
Presenter: James Chih-Hsin Yang
Session: e-Poster Display Session
397P - A phase I cohort expansion trial of OBI-833 in non-small cell lung cancer patients
Presenter: Ching-Liang Ho
Session: e-Poster Display Session
398P - Real-world mechanism of crizotinib-resistance in MET exon 14 skipping mutations non-small-cell lung cancer using next generation sequencing: A multicenter study
Presenter: Dong Wang
Session: e-Poster Display Session
399P - Real-world insights into patients (pts) with advanced NSCLC and MET alterations
Presenter: Marisa Bittoni
Session: e-Poster Display Session
400P - Sequential afatinib and osimertinib in real-world EGFR mutation positive (EGFRm+) NSCLC: Final analysis of Asian patients in the GioTag study
Presenter: Maximilian J. Hochmair
Session: e-Poster Display Session
401P - A prospective, phase II trial of low-dose afatinib monotherapy for patients with EGFR, mutation-positive, non-small cell lung cancer (TORG1632)
Presenter: Satoshi Igawa
Session: e-Poster Display Session
402P - Efficacy and safety of sintilimab plus docetaxel in patients with previously treated advanced non-small cell lung cancer (NSCLC)
Presenter: Zhehai Wang
Session: e-Poster Display Session