Muhammad Adnan Khattak

Muhammad Adnan Khattak
Royal Perth Hospital · Department of Oncology

MBBS, FRACP

About

70
Publications
5,947
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1,163
Citations

Publications

Publications (70)
Article
PURPOSE Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03...
Article
9581 Background: Adjuvant pembro improved RFS vs placebo (HR, 0.61; 95% CI, 0.45-0.82) and had manageable safety in patients (pts) with resected high-risk stage II melanoma at second interim analysis of KEYNOTE-716 (NCT03553836). HRQoL results are presented. Methods: Pts aged ≥12 y with resected stage IIB/C melanoma were randomized 1:1 to adjuvant...
Article
Background Pembrolizumab prolongs progression-free and overall survival among patients with advanced melanoma and recurrence-free survival in resected stage III disease. KEYNOTE-716 assessed pembrolizumab as adjuvant therapy in patients with completely resected, high-risk, stage II melanoma. We report results from the planned first and second inter...
Preprint
Background: Predictive biomarkers of response to immune checkpoint inhibitors (ICI) are currently being evaluated in many studies. We evaluated whether germline Human Leukocyte Antigen (HLA) status can influence the response to immunotherapy. Materials and Methods: Advanced melanoma patients undergoing treatment with pembrolizumab were recruited be...
Article
Full-text available
Purpose Although exercise medicine is recommended to counter treatment-related side-effects and improve health-related outcomes of patients affected by different cancers, no specific recommendations exist for patients with melanoma. As a result, we systematically examined the current evidence regarding the effects of physical activity and exercise...
Article
Full-text available
Background The validity of circulating tumour DNA (ctDNA) as an indicator of disease progression compared to medical imaging in patients with metastatic melanoma requires detailed evaluation. Methods Here, we carried out a retrospective ctDNA analysis of 108 plasma samples collected at the time of disease progression. We also analysed a validation...
Article
9571 Background: Adjuvant anti-PD1 therapy reduces the risk of recurrence in resected stage III/IV melanoma and is now standard care. Limited data exist beyond registration trials. We sought to explore the use of adjuvant immunotherapy in routine clinical practice. Methods: Patients (pts) from 11 Australian centres who received adjuvant nivolumab (...
Article
9578 Background: Adjuvant (adj) radiotherapy (RT) halves the risk of locoregional (LR) recurrence in patients (pts) with high risk stage III melanoma after lymphadenectomy (CLND), however its role in the adj immunotherapy (IO) era without CLND is unknown. Methods: Pts with resected stage III melanoma who received adj IO and recurred with resectable...
Conference Paper
Background: Anti-PD-1 therapy has improved the outcome of advanced melanoma patients with a 5-year survival rate of about 40-45%. However, biomarkers predictive of response to immune checkpoint blockade therapy are lacking. There is limited data on the utility of host germline human leucocyte antigen (HLA) genotype as a predictor of response to ant...
Article
Full-text available
In this study, we evaluated the predictive value of circulating tumour DNA (ctDNA) to inform therapeutic outcomes in metastatic melanoma patients receiving systemic therapies. We analysed 142 plasma samples from metastatic melanoma patients prior to commencement of systemic therapy: 70 were treated with BRAF/MEK inhibitors and 72 with immunotherapi...
Article
Purpose: We evaluated the predictive value of pretreatment ctDNA to inform therapeutic outcomes in patients with metastatic melanoma relative to type and line of treatment. Experimental design: Plasma circulating tumor DNA (ctDNA) was quantified in 125 samples collected from 110 patients prior to commencing treatment with immune checkpoint inhib...
Article
Full-text available
The analysis of plasma circulating tumour nucleic acids provides a non-invasive approach to assess disease burden and the genetic evolution of tumours in response to therapy. BRAF splicing variants are known to confer melanoma resistance to BRAF inhibitors. We developed a test to screen cell-free RNA (cfRNA) for the presence of BRAF splicing varian...
Article
Full-text available
Background We aimed to assess the impact of genomic human leukocyte antigen (HLA)-I/II homozygosity on the survival benefit of patients with unresectable locally advanced, metastatic non-small lung cancer treated by single-agent programmed cell death protein-1/programmed death ligand 1 (PD1/PDL1) inhibitors. Methods We collected blood from 170 pat...
Article
Full-text available
Background: The development of biomarkers predictive of response to immune checkpoint inhibitor (ICI) therapies in advanced melanoma is an area of great interest in oncology. Our study evaluated the potential role of serum vascular endothelial growth factor (VEGF) as a predictive biomarker of clinical benefit and response to treatment with ICIs. Me...
Article
Circulating tumour cells (CTCs) can be assessed through a minimally invasive blood sample with potential utility as a predictive, prognostic and pharmacodynamic biomarker. The large heterogeneity of melanoma CTCs has hindered their detection and clinical application. Here we compared two microfluidic devices for the recovery of circulating melanoma...
Article
Full-text available
Background: PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab. Methods: Blood samples were collected from patien...
Article
The analysis of circulating tumor DNA provides a minimally invasive molecular interrogation that has the potential to guide treatment selection and disease monitoring. Here, the authors evaluated a custom UltraSEEK melanoma panel for the MassARRAY system, probing for 61 mutations over 13 genes. The analytical sensitivity and clinical accuracy of th...
Data
Fig. S1. Comparison of number SNVs in patients with and without NF1 mutations. Fig. S2. Percent concordance of SNVs in tissue and plasma biopsies by NGS or NGS plus ddPCR.
Data
Table S2. NGS mutational profile of study cohort.
Data
Table S4. Time‐lapse of tissue and plasma biopsies (weeks) obtained for the study cohort.
Data
Table S3. Comparison of SNVs in tissue and plasma biopsies.
Article
Full-text available
Cutaneous melanoma circulating tumour cells (CTCs) are phenotypically and molecularly heterogeneous. We profiled the gene expression of CTC subpopulations immunomagnetic-captured by targeting either the melanoma-associated marker, MCSP, or the melanoma-initiating marker, ABCB5. Firstly, the expression of a subset of melanoma genes was investigated...
Article
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Background: A significant number of melanoma patients experience recurrence to distant sites, despite having had surgical treatment of the primary lesion, with curative intent. Monitoring of patients for early evidence of disease recurrence would significantly improve management of the disease, allowing timely therapeutic intervention. Circulating...
Article
Full-text available
Circulating tumor DNA (ctDNA) may serve as a surrogate to tissue biopsy for non‐invasive identification of mutations across multiple genetic loci and for disease monitoring in melanoma. In this study, we compared the mutation profiles of tumor biopsies and plasma ctDNA from metastatic melanoma patients using custom sequencing panels targeting 30 me...
Article
Full-text available
Background: Circulating tumour DNA (ctDNA) may serve as a measure of tumour burden and a useful tool for non-invasive monitoring of cancer. However, ctDNA is not always detectable in patients at time of diagnosis of metastatic disease. Therefore, there is a need to understand the correlation between ctDNA levels and the patients' overall metabolic...
Article
Purpose To evaluate the feasibility of using circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) for the management of uveal melanoma (UM). Patients and Methods Low-coverage whole-genome sequencing was used to determine somatic chromosomal copy number alterations (SCNAs) in primary UM tumors, ctDNA, and whole-genome amplified CTCs. CT...
Article
Full-text available
Background Currently mainly BRAF mutant circulating tumor DNA (ctDNA) is utilized to monitor patients with melanoma. TERT promoter mutations are common in various cancers and found in up to 70% of melanomas, including half of BRAF wild-type cases. Therefore, a sensitive method for detection of TERT promoter mutations would increase the number of pa...
Article
Full-text available
Circulating Tumour Cells (CTCs) are promising cancer biomarkers. Several methods have been developed to isolate CTCs from blood samples. However, the isolation of melanoma CTCs is very challenging as a result of their extraordinary heterogeneity, which has hindered their biological and clinical study. Thus, methods that isolate CTCs based on their...
Article
To investigate whether any survival differences existed between advanced cancer patients treated in metropolitan Perth and those treated in regional Western Australia (WA). Retrospective study. Advanced cancer patients treated through medical oncology clinics at Royal Perth Hospital and regional cancer centres (Kalgoorlie, Albany, Geraldton and Nor...
Article
Full-text available
Before licensing, ipilimumab was first made available to previously treated advanced melanoma patients through an expanded access programme (EAP) across Europe. We interrogated data from UK EAP patients to inform future clinical practice. Clinicians registered in the UK EAP provided anonymized patient data using a prespecified variable fields datas...
Article
Full-text available
Repeat tumor biopsies to study genomic changes during therapy are difficult, invasive and data are confounded by tumoral heterogeneity. The analysis of circulating tumor DNA (ctDNA) can provide a non-invasive approach to assess prognosis and the genetic evolution of tumors in response to therapy. Mutation-specific droplet digital PCR was used to me...
Article
Background Aromatase inhibitors (AIs) reduce the risk of breast cancer recurrence in hormone receptor positive breast cancers by blocking the production of estrogen. Low estrogen states are also associated with reduction of bone mineral density. AIs have been shown to lead to reduction in bone mineral density although the degree of change in bone m...
Article
Background: Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy in combination with chemotherapy in the first-line therapy of advanced colorectal cancer (CRC). Data from randomized studies comparing these monoclonal antibodies as initial therapy is conflict...
Article
Background The prognostic significance of various systemic inflammation-based markers has been explored in different cancers. These markers can be used to assist with decision making in oncology clinics.AimThe aim of this study was to investigate the prognostic significance of three systemic inflammation-based factors: neutrophil-lymphocyte ratio (...
Article
3018 Background: Since publication of the registration trial in 2010 (Hodi et al, NEJM 2010;363:711-23), real world use of ipilimumab (Ipi) in previously treated advanced melanoma patients has extended beyond the specific trial entry criteria of ECOG PS 0-1. We undertook a review of UK patients (pts) treated in the international EAP prior to Europe...
Article
Full-text available
Metastatic melanoma is one of the most challenging malignancies to treat and often has a poor outcome. Until recently, systemic treatment options were limited, with poor response rates and no survival advantage. However, the treatment of metastatic melanoma has been revolutionized by developments in targeted therapy and immunotherapy; the BRAF inhi...
Article
Renal cell carcinoma comprises 2-3 % of all adult malignancies and its incidence is increasing. Overall survival of patients with advanced disease has increased over the last decade due to the development of many effective targeted agents. Unfortunately, most patients inevitably develop resistance to these agents. While our understanding of the und...
Article
Full-text available
astatic renal cell carcinoma (mRCC) has been made over the last 5 years, with a plethora of targeted agents currently approved in different clinical settings. However, not all mRCC patients respond to treatment with these drugs and currently there are no validated biomarkers to predict clinical outcome. We therefore read with interest Armstrongetal...
Article
Uveal melanoma (UM) is a rare disease with a distinct molecular profile. About half of the patients with UM eventually develop metastatic disease. The prognosis of these patients remains poor. Treatment options are limited and none of them have been able to show a survival benefit. Ipilimumab was the first agent to show a survival benefit in patien...
Conference Paper
Full-text available
Background Study results demonstrated that IFN augments BEV activity and improves median PFS in pts with mRCC. Thus, combination BEV + IFN is a standard first-line treatment option for mRCC. Combining BEV with the mTOR inhibitor EVE may be an efficacious and well-tolerated treatment option. The open-label, phase II RECORD-2 trial compared first-lin...
Article
Introduction Sunitinib is a standard 1st line treatment for advanced renal cell carcinoma (RCC) but 2/3rd of patients do not respond to treatment and the 2 weeks ‘off’ treatment is sometimes associated with tumour regrowth and recrudescence of disease symptoms. Both sunitinib and low dose metronomic cyclophosphamide (Sun-Cyclo) are anti-angiogenic...
Article
Background: Colorectal cancer is the third most common cancer in Australia. The median overall survival for metastatic colorectal cancer is nearly 2 years. However, there may be survival differences based on site of metastatic disease. Methods: Data was collected from the South Australian Registry for Advanced Colorectal Cancer. A total of 1207...
Article
Full-text available
The incidence of esophagogastric cancers is increasing rapidly in the Western population. Despite better understanding of the biology and intense research in the treatment of these cancers, the long-term survival remains poor both in the locally advanced and metastatic settings. The addition of combined modality strategies has resulted in modest im...
Article
Oxaliplatin-based chemotherapy regimens are the current standard treatment in the management of colorectal cancer. Neurotoxicity is the major cause of treatment delay, dose reduction, and cessation of oxaliplatin. Evidence regarding the role of calcium and magnesium prophylaxis to prevent oxaliplatin-related neurotoxicity is conflicting and further...
Article
Age is a major risk factor for development of sporadic colorectal cancer but elderly patients are underrepresented in clinical trials and are potentially offered chemotherapy less often. Data were obtained from South Australian Clinical Registry for advanced colorectal cancer between 1st February 2006 and 9th September 2010. Patients who received c...
Article
Small cell lung cancer (SCLC) with ectopic adrenocorticotropic hormone (ACTH) syndrome and resultant hypercortisolism carries a poor prognosis with a short median survival and high incidence of infective complications. The combination of etoposide with either carboplatin or cisplatin is the current standard chemotherapy used for the management of S...
Article
Full-text available
Wilms' tumor is one of the most common pediatric malignancies. Survival rates have increased dramatically over the last few decades. This increased survival means that there is an ever growing population of patients susceptible to the late effects of their initial therapy. Survivors of Wilms’ tumor have a substantially higher rate of development...

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