Damien Kee

Damien Kee
Austin Health · Unit of Medical Oncology

MB BS DMedSci FRACP

About

49
Publications
6,237
Reads
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3,210
Citations
Additional affiliations
January 2009 - December 2012
Peter MacCallum Cancer Centre

Publications

Publications (49)
Article
RAF inhibitors are effective against melanomas with BRAF V600E mutations but may induce keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cSCCs). The potential of these agents to promote secondary malignancies is concerning. We analyzed cSCC and KA lesions for genetic mutations in an attempt to identify an underlying mechanism for thei...
Article
Melanoma is resistant to cytotoxic therapy, and treatment options for advanced disease have been limited historically. However, improved understanding of melanoma driver mutations, particularly those involving the mitogen-activated protein kinase pathway, has led to the development of targeted therapies that are effective in this previously treatme...
Article
Full-text available
Background Patients with rare cancers represent 55% of all gynecological malignancies and have poor survival outcomes due to limited treatment options. Combination immunotherapy with the anti-programmed cell death protein 1 (anti-PD-1) antibody nivolumab and the anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab has...
Article
Full-text available
Background Melanoma brain metastases (MBMs) are a challenging clinical problem with high morbidity and mortality. Although first-line dabrafenib–trametinib and ipilimumab–nivolumab have similar intracranial response rates (50%–55%), central nervous system (CNS) resistance to BRAF-MEK inhibitors (BRAF-MEKi) usually occurs around 6 months, and durab...
Article
e18581 Background: Rare cancers (RC) occur at incidence < 6/100,000 and accessing treatment and evidence-based care can be challenging. Australia’s geographical distance adds complexity when referring to RC sub-specialists, clinical trials or research. The Australian Rare Cancer (ARC) Portal aims to address this unmet need. Methods: The ARC Portal...
Article
3073 Background: Comprehensive genomic profiling (CGP) is increasingly used to guide therapy selection in advanced cancer patients who have exhausted standard therapy options. Here we assess the utility of Therapy Oriented Precision Oncology Guidelines for Recommending Anticancer Pharmaceuticals (TOPOGRAPH) to guide matching of drug treatments base...
Article
In high-grade serous ovarian carcinoma (HGSC), deleterious mutations in DNA repair gene RAD51C are established drivers of defective homologous recombination and are emerging biomarkers of PARP inhibitor (PARPi) sensitivity. RAD51C promoter methylation (meRAD51C) is detected at similar frequencies to mutations, yet its effects on PARPi responses rem...
Article
Full-text available
Background: Adrenocortical carcinoma is a rare malignancy, with poor prognosis and limited treatment options for patients with advanced disease. Chemotherapy is the current standard first-line treatment, providing only a modest survival benefit. There is only limited treatment experience with immunotherapy using single-agent anti-PD-1/PD-L1 therapy...
Preprint
Full-text available
While loss of BRCA1 promoter methylation has been shown to cause PARP inhibitor (PARPi) resistance in high-grade serous ovarian carcinoma (HGSC), the impacts of RAD51C methylation (me RAD51C ) remain unresolved. In this study, two PARPi-responsive HGSC patient-derived xenografts (PDX) with RAD51C gene silencing and homologous recombination deficien...
Conference Paper
Aims Rare cancers (RCs) are difficult to research and consequently often lack evidence-based treatments. Identifying underlying genomic biomarkers may allow more rational selection of treatments or clinical trials. We report treatment and survival in RC patients (pts) following next-generation sequencing (NGS) in the NOMINATOR study (ACTRN12616001...
Article
Full-text available
Purpose: We aimed to investigate the role of FDG-PET/CT in monitoring of response and immune-related adverse events (irAEs) following first-line combination-immune checkpoint inhibitor (combination-ICI) therapy for advanced melanoma. Methods: We retrospectively reviewed outcomes in patients who had (1) first-line nivolumab plus ipilimumab; (2) p...
Article
Importance Biliary tract cancers represent a rare group of malignant conditions with very limited treatment options. Patients with advanced disease have a poor outcome with current therapies. Objective To evaluate the efficacy and safety of combination immunotherapy with nivolumab and ipilimumab in patients with advanced biliary tract cancers. De...
Article
Immune-related adverse events (irAEs) are a frequent complication of immunotherapy, but neurological irAEs are rare and varied. Here, we present a case of cerebral amyloid angiopathy-related inflammation (CAA-ri) attributable to nivolumab monotherapy, which has not been previously reported. The context of immunotherapy and availability of serial im...
Article
Purpose: Combination immunotherapy with anti-CTLA-4 and anti-PD-1 blockade has demonstrated significant clinical activity across several tumour types. Neuroendocrine tumors (NETs) are a heterogeneous group of rare tumors with limited treatment options. CA209-538 is a clinical trial of combination immunotherapy with ipilimumab and nivolumab in rare...
Article
6091 Background: Up to 50% of gynecological cancers are considered rare. The outcome of these patients (pts) is poor given a lack of scientific and clinical knowledge. Immunotherapy using single agent anti- PD-1/PD-L1 treatment (tx) has shown only modest activity in patients with common gynecological malignancies, such as high grade serous ovarian...
Article
2033 Background: Despite increasing evidence of benefit supporting CGP in personalizing cancer therapy, its widespread uptake remains limited. Barriers include low patient understanding, unmet patient expectations related to low utility, clinician concerns over cost-effectiveness, perceived value, and discomfort in management of complex genomic res...
Article
103 Background: Rare cancers (RCs) often lack proven treatments and consequently have poorer outcomes. Identification of molecular biomarkers can facilitate treatment selection and trials access for RC patients (pts) where histology-based trials are not feasible. We assessed the potential for next-generation sequencing (NGS) to impact RC care. Meth...
Article
4588 Background: Patients (pts) with advanced biliary tract cancers (BTC) have a poor prognosis with first and second line chemotherapy resulting in modest survival benefits. Immunotherapy using single agent anti-PD-1 therapy has also shown low activity with an objective response rate (ORR) of less than 10%. Combined CTLA-4/PD-1 blockade using ipil...
Article
10041 Background: Predictors of outcomes of immune checkpoint inhibitors (ICI) are desirable. We aim to investigate the prognostic value of ¹⁸ F-fluorodeoxyglucose-PET/CT (FDG-PET) parameters at baseline and response monitoring of patients (pts) with advanced melanoma receiving ipi/nivo. Methods: From 2016-2019, melanoma pts who received ipi/nivo a...
Article
There is now evidence that gene fusions activating the MAPK pathway are relatively common in pancreatic acinar cell carcinoma with potentially actionable BRAF or RET fusions being found in ~30%. We sought to investigate the incidence of RAF1 fusions in pancreatic malignancies with acinar cell differentiation. FISH testing for RAF1 was undertaken on...
Article
Full-text available
PURPOSE Rare cancers are challenging for researchers, as clinicians and scientists have difficulty recruiting sufficient patient cases to power studies appropriately. Likewise, patients often are frustrated by a lack of specific information or evidence base for their cancer and, although eager to participate in research, have limited opportunities....
Article
Full-text available
Background: Autoimmune polyendocrine syndrome type II (APS-2) is a rare constellation of autoimmune hypoadrenalism, thyroid dysfunction and/or type 1 diabetes (T1DM), usually occurring in the 3rd or 4th decades and associated with a human leukocyte antigen (HLA) DR3 or DR4 serotype. We detail the first report of an elderly woman developing the ful...
Article
Our aim was to investigate sebaceous differentiation in thymus tumours and to identify new actionable genomic alterations. To this end we screened 35 normal and 23 hyperplastic thymuses, 127 thymomas and 41 thymic carcinomas for the presence of sebaceous differentiation as defined by morphology and expression of adipophilin and androgen receptor (A...
Article
2570 Background: Patients (pts) with rare cancers represent an unmet medical need and have an inferior overall survival compared to patients with more common malignancies. Due to their low frequency, no therapies, including immunotherapies, have systematically been investigated in this population. Ipilimumab (ipi)/Nivolumab (nivo) combination treat...
Article
Abstract Importance: Rheumatic immune-related adverse events (irAEs) occur in approximately 10-20% of anti-programmed death 1 (anti-PD1) treated cancer patients. There are limited data on the natural history, optimal treatment and long-term oncological outcomes of patients with rheumatic irAEs. Objective: The objective of the study was to describe...
Article
Full-text available
Background: As early detection of recurrent melanoma maximizes treatment options, patients usually undergo post-operative imaging surveillance, increasingly with FDG-PET/CT (PET). To assess this, we evaluated stage 3 melanoma patients who underwent prospectively applied and sub-stage-specific schedules of PET surveillance. Patients and methods:...
Article
Full-text available
Purpose Circulating tumor DNA (ctDNA) allows noninvasive disease monitoring across a range of malignancies. In metastatic melanoma, the extent to which ctDNA reflects changes in metabolic disease burden assessed by ¹⁸ F-labeled fluorodeoxyglucose positron emission tomography (FDG-PET) is unknown. We assessed the role of ctDNA analysis in combinatio...
Article
9563 Background: With the evolving treatment landscape in metastatic melanoma, approaches to disease surveillance post resection in stage 3 disease requires reconsideration. We previously reported the outcomes of sub-stage-specific schedules of combined fluorodeoxyglucose-positron emission and computerized tomography (PET/CT) surveillance at high r...
Article
Immunotherapy for advanced melanoma has progressed dramatically in the last five years with the approval of immune checkpoint inhibitors targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Inhibition of these targets can break cancer-immune tolerance and result in durable objective responses wi...
Chapter
Advances in our understanding of immune checkpoints and the mitogen-activated protein kinase pathway (MAPK) have driven substantial improvements in systemic treatments for melanoma. The MAPK pathway is a key oncogenic signaling system which drives melanoma metastasis, proliferation, and survival. The discovery of BRAF V600 mutations which are found...
Article
This is a retrospective analysis addressing the impact of immune check-point blockers on pre-existing autoimmune diseases in patients with metastatic melanoma. Ipilimumab, an anti-CTLA-4 antibody, is the first and most well studied immune checkpoint inhibitor in melanoma, however, due to concerns about immune related adverse events, patients with p...
Article
Background Addition of a MEK inhibitor to a BRAF inhibitor enhances tumour growth inhibition, delays acquired resistance, and abrogates paradoxical activation of the MAPK pathway in preclinical models of BRAF-mutated melanoma. We assessed the safety and efficacy of combined BRAF inhibition with vemurafenib and MEK inhibition with cobimetinib in pat...
Article
Full-text available
Objectives: To evaluate the efficacy and tolerability of ipilimumab in an Australian clinical setting, and to assess the association of response with melanoma subtype, BRAF mutation status, absolute lymphocyte count and incidence of serious immune-related adverse events (AEs). Design, setting and participants: Retrospective review of patients wi...
Article
Full-text available
Since its approval by the US Food and Drug Administration in February 2002, the tyrosine kinase inhibitor, imatinib, has become the standard of care for patients with metastatic or unresectable KIT-positive gastrointestinal stromal tumors (GISTs). Imatinib functions by blocking the adenosine triphosphate binding site of the constitutively activated...
Article
Full-text available
Cutaneous squamous-cell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors. We performed a molecular analysis to identify oncogenic mutations (HRAS, KRAS, NRAS, CDKN2A, and TP53) in the lesions from patients treated with the BRAF inhibitor vemurafenib. An analysis of an independent validation set and functi...
Conference Paper
Background: The significance of melanoma pigmentation is poorly studied despite being fundamental to melanocyte biology. We examined its pathological and clinical associations in primary melanoma; and as a diagnostic target for the novel melanin binding PET tracer [18F]MEL050 in advanced melanoma. Methods: Data collected prospectively from 253 pati...
Article
BRAF is an attractive target for melanoma drug development. However, resistance to BRAF inhibitors is a significant clinical challenge. We describe a model of resistance to BRAF inhibitors developed by chronic treatment of BRAF(V)⁶⁰⁰(E) melanoma cells with the BRAF inhibitor SB-590885; these cells are cross-resistant to other BRAF-selective inhibit...

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