Safety of pazopanib and sunitinib in treatment-naive patients with metastatic renal cell carcinoma: Asian versus non-Asian subgroup analysis of the COMPARZ trial

Arun Azad et al. published in the Journal of Hematology & Oncology.

From Lucas Heights to PeterMac, new prostate therapy is a game-changer

Arun Azad reported in The Age.

Monash research sheds light on prostate cancer treatment

Associate Professor Arun Azad and the 

Prostate Cancer Therapeutics research group

Monash University research has revealed that prostate cancer patients with a particular biomarker may benefit from commonly used hormonal drugs, contrary to a landmark study published a few years ago.

Monash Health oncologist Associate Professor Arun Azad from the Prostate Cancer Therapeutics laboratory, School of Clinical Sciences at Monash Health (SCS) led the study that will change clinical practice and may improve outcomes for patients with metastatic castration-resistant prostate cancer. 

“A landmark study published in 2014 had suggested that men with a certain biomarker (known as AR-V7) do not respond to some of the commonly used hormonal drugs in prostate cancer,” Associate Professor Azad said.

AR-V7, a type of protein, is easily detected in the blood of men with prostate cancer.

“In our study, we’ve shown that patients with AR-V7 may in fact respond to the drugs abiraterone and enzalutamide, and should not necessarily be excluded from such therapies if they express this biomarker.”

The study, published last week in European Urology, supports a recent pivotal phase III clinical trial that made the same finding.

Associate Professor Azad said his group’s research shows that the presence of AR-V7 should not be used to guide treatment selection for men with advanced prostate cancer.

“This represents a major shift in our understanding of AR-V7 and its potential clinical utility as a biomarker,” he said. 

“This is a pertinent reminder that we should not ‘jump the gun’ with biomarker studies and make assumptions—or even worse, change our clinical practice—on the basis of a solitary study.” 

Associate Professor Azad’s research was supported by an NHMRC Project Grant on which he is the Chief Investigator. 

He thanks the patients and families who so generously supported this ongoing study, as well as his research team, clinical collaborators at Monash Health, Eastern Health and Chris O'Brien, Lifehouse.

Expression of Androgen Receptor Splice Variant 7 or 9 in Whole Blood Does Not Predict Response to Androgen-Axis-targeting Agents in Metastatic Castration-resistant Prostate Cancer

Arun Azad et al. published in European Urology.

Read article here.

Circulating tumor DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer

Arun Azad et al. published in Cancer Discovery.

Read article here.

Monash-led clinical trial shows promise for prostate cancer patients

Associate Professor Arun Azad

A world-first clinical trial aimed at improving immunotherapy responses in patients with advanced prostate cancer has started at the Monash HealthTranslation Precinct.

The trial, which has already seen positive results, is being led by Monash Health oncologist AssociateProfessor Arun Azad from the Prostate Cancer Therapeutics laboratory, School of Clinical Sciences at Monash Health (SCS). 

“The first patient on trial has responded to therapy after just six weeks, which is pretty remarkable,” Associate Professor Azad said. 

The investigator-initiated trial is known as ICE-PAC (Immune checkpoint inhibition + stereotactic radiation in advanced prostate cancer), and is supported with funding from Merck Serono, the manufacturer of Avelumab—the drug being used in the trial.

Associate Professor Azad said immunotherapy has transformed the management of many malignancies—although not prostate cancer (yet)—by re-activating anti-tumour immune responses against cancer cells.

“However, these drugs do not work in all patients and in particular in advanced prostate cancer, seem to have limited activity at best,” Associate Professor Azad said.

“One way to boost their efficacy might be pre-treating with high-dose, precision radiotherapy (also known as stereotactic radiation) to metastatic disease.”

“This stereotactic radiation causes death of cancer cells, which releases tumour antigens (proteins) that stimulate immunity and can enhance the effect of immunotherapy drugs such as Avelumab.”  ​

​Associate Professor Azad said the patients being recruited to this study are heavily pre-treated having progressed on standard chemotherapy and hormonal therapy.

“They have limited treatment options and sadly in some cases limited prognosis. So we badly need effective new treatment options for them,” Associate Professor Azad said.

Collaborators on the study include Associate Professor Shankar Siva and Dr Ben Tran from Peter MacCullum Cancer Centre and Dr Carmel Pezaro, Eastern Health.

​

The researcher team will recruit a total of 25 patients. Three patients are on the trial now with another two about to commence. ​

Monash prostate cancer research highlighted at scientific conferences

Dr Sarah To

Congratulations Dr Sarah To and Ms Heidi Fettke from the Prostate Cancer Therapeutics laboratory, who have been selected present their research at forthcoming conferences.

Postdoctoral researcher Dr To will present at the AACR Special Conference on Prostate Cancer in Orlando in December while PhD candidate Ms Fettke will present at the 4th Thomas Ashworth CTC and Liquid Biopsy Symposium in Sydney next week.

Ms Heidi Fettke

The Prostate Cancer Therapeutics laboratory headed by Associate Professor Arun Azad focuses on circulating androgen receptor variants in prostate cancer patients.

"Binding of androgens such as testosterone to the androgen receptor (AR) fuels the growth of prostate cancer cells,” Associate Professor Azad said.

“Therefore, the mainstay of treating advanced prostate cancer is to lower androgen levels within the body using androgen deprivation therapy (ADT).”

Androgen receptor splice variants (ARVs) are altered forms of the AR which are continuously activated and have been linked to resistance to ADT.

Associate Professor Azad’s group has now shown that detection of ARVs within the blood is not in fact associated with resistance to ADT.

“These findings are supported by the results of a recent pivotal clinical trial and have potentially key implications for the use of ADT in men with advanced prostate cancer", Associate Professor Azad said.

Monash Health recruits first patient in Australia to prostate cancer clinical trial

Associate Professor Arun Azad

The first Australian to be recruited to a new prostate cancer clinical trial is a Monash Health patient.

Led by Associate Professor Arun Azad, Head of Medical Oncology Clinical Trials at the Monash Health Translation Precinct (MHTP), the PROfound trial examines the benefit of a new drug, olaparib, that targets the PARP gene (a gene involved in repairing DNA) in advanced prostate cancer.

“PARP inhibitors work by inhibiting a key DNA damage repair pathway in prostate cancer cells,” Associate Professor Azad said.

“Approximately 20% of advanced prostate cancer patients harbour a DNA repair gene mutation that makes them very sensitive to the effects of PARP inhibitors.”

The same mutations can be present in breast and ovarian cancer, for which olaparib is already approved and in the clinic.

“We know that advanced prostate cancer patients with a DNA repair gene mutation have really bad outcomes,” Associate Professor Azad said.

“However, the use of PARP inhibitors allows us to take advantage of these mutations for the benefit of patients. We hope that these drugs will eventually become available in the clinic for advanced prostate cancer patients, pending the success of trials such as PROfound.”

The PROfound clinical trial is being conducted at the state-of-the-art Clinical Trial Centre at the Monash Health Translation Precinct.   

Associate Professor Azad is a Senior Research Fellow at Monash University and Consultant Medical Oncologist at Monash Health.

SCS student wins top prize in Immunology

SCS PhD student Ms Heidi Fettke

Congratulations Heidi Fettke, a translational PhD student at the School of Clinical Sciences at Monash Health (SCS), who has been awarded the prestigious Nairn Prize in Immunology.

The Nairn Prize is given to the top Honours student each year enrolled in immunology at Monash University.

Heidi was awarded the Nairn Prize in Immunology for her Bachelor of Science (Honours) project, where she investigated the potential role of the c-Myc oncogene in driving expression of an immuno-inhibitory molecule, PD-L1, in glioblastoma tumours (a lethal brain cancer).  Heidi completed her project under the supervision of Professor Terrance Johns, Centre for Cancer Research at the Hudson Institute of Medical Research.

Heidi is currently researching biomarkers in metastatic castration-resistant prostate cancer under the supervision of Associate Professor Arun Azad, Department of Medicine.

Lung cancer patients to benefit from clinical trials at Monash Health Translation Precinct

CTC Manager Ms Cheryl Coleman, Professor Eva Segelov
and oncology patient Ms Marnie Dalton

Monash Health lung cancer patients are set to benefit from the relocation of clinical trials to the state-of-the-art Clinical Trials Centre at the Monash Health Translation Precinct (MHTP) in Clayton.

Lung cancer is the fifth most common cancer in Australia but the leading cause of cancer related deaths.  Monash Health receives over 250 new referrals of lung cancer each year, one of the highest patient loads in Victoria, as our area serves a population equivalent to the size of the Adelaide.

“All lung cancer clinical trials are being moved from the Monash Cancer Centre, Moorabbin to the MHTP Clinical Trials Centre, the ‘home base’ for Monash Health and Monash University clinician-scientists to conduct early, mid and late phase clinical trials,” said Dr Muhammad Alamgeer, medical oncologist and lung trials clinical lead at MHTP.

“Currently there are eight clinical trials are being conducted in various subtypes of lung cancer—of these, two trials are phase 2 and the rest are phase 3.  

A number of other patients with lung cancer are also participating in phase 1 clinical trials, which are already running at MHTP.

Dr Alamgeer said the Monash team of motivated and world-class clinicians and researchers strive to ensure patients have access to the latest and most effective treatments, and that further early and late phase clinical trials are planned to start in the coming months.

 “Participation in clinical trials gives our patients the opportunity to receive novel and cutting-edge treatment options,” said Monash University’s Associate Professor Arun Azad, oncologist and Head of Oncology Clinical Trials at MHTP.

“Every cancer patient at Monash Health who is either newly diagnosed or is requiring a change in their treatment is considered for participation in a clinical trial,” said Associate Professor Azad.

Associate Professor Azad said that due to stringent entry criteria, not all patients are eligible to participate in a clinical trial.

Director of Oncology at Monash Health, Professor Eva Segelov said recent advances in medical research have led to the discovery of novel and more effective treatments, resulting in improvements in overall survival and quality of life for lung cancer patients.

“We are very fortunate to have the Clinical Trials Centre, a purpose-built facility supported by dedicated staff with expertise in clinical trials, ranging from pharmacy to nursing, data management and medical care, to our translational scientists who work alongside us to better understand cancer biology,” said Professor Segelov from the Department of Medicine, School of Clinical Sciences at Monash Health.

“Collaborative initiatives at the MHTP bring together information and leading opinion from clinicians and scientists on cancer treatment, prevention, diagnosis and cure.”

“We have planned to move all cancer clinical trials to the MHTP, optimising translational research opportunities, which will result in better outcomes for our patients,” said Professor Segelov.

Monash clinician-researcher recognised for work on prostate cancer

Associate Professor Arun Azad

Congratulations Associate Professor Arun Azad on his recent academic promotion in the Department of Medicine, School of Clinical Sciences at Monash Health, Monash University. 

A Consultant Medical Oncologist at Monash Health, Associate Professor Azad’s clinical and research work is focused on urological malignancies, especially prostate cancer.

Associate Professor Azad completed his medical oncology training and a PhD in Melbourne before embarking on a fellowship at the University of British Columbia in Vancouver, where he led cutting-edge work investigating mechanisms of therapeutic resistance and response in advanced prostate cancer patients through genomic analysis of circulating cell-free DNA (cfDNA) at the British Columbia Cancer Agency. 

Since taking up his position at the Monash Health Translation Precinct (MHTP) in 2015, Associate Professor has been actively involved in clinical trials with novel drug treatments and translational biomarker studies. 

Associate Professor Azad’s clinical and research activities have resulted in a strong academic record with numerous high-impact publications and over $4.5M in competitive funding. 

Since returning from Canada, he has also taken a key leadership role in the Australian uro-oncology community as Chair, Translational Research Committee of the ANZUP Clinical Trials Group. 

Associate Professor Azad said he is very pleased to receive this promotion, which is a nice recognition for his clinical and academic endeavours over recent years. 

“I am especially grateful to my family especially my wife and parents, and my mentors both in Canada and Australia,” he said.

VCA grant brings personalised cancer therapy one step closer

Dr Arun Azad

A world-first clinical trial at Monash Health Translation Precinct, funded by a Victorian Cancer Agency (VCA) grant, will determine if a new class of drug is effective in prostate and colorectal cancer patients.

Prostate and colorectal cancers are two of the most commonly diagnosed cancers in Australia.  More than 3000 men die of prostate cancer and over 4100 lives are claimed by colorectal cancer every year in Australia.

Researchers at Monash University and the Hudson Institute of Medical Research have received a highly competitive VCA grant worth $2 million to determine whether particular prostate and colorectal cancer patients will respond to a new class of cancer drug known as BET inhibitors.

“BET inhibitors are a new type of therapy that can slow down the growth of cancers by switching off cancer genes,” said lead researcher Dr Arun Azad, Senior Research Fellow at Monash University and Consultant Medical Oncologist at Monash Health. 

Unlike chemotherapy which indiscriminately attacks ‘good’ and ‘bad’ cells, BET inhibitors—a type of epigenetic therapy—work on a genetic level to turn off the growth of cancer cells.

“We believe that patients who have a particular biomarker known as long non-coding RNAs may respond best to BET inhibitor therapy.”

“Importantly, we can easily identify which patients have these long non-coding RNA biomarkers through examining their tissue sample,” added Dr Azad.

Dr Azad believes around 50% of prostate and colorectal cancer patients have the RNA biomarker and predicts these patients will respond well to the new class of drug.

“While there are other trials investigating BET inhibitors, our clinical trial is the first in the world to look at the association between patients with RNA molecules and BET inhibitors.”

“We’re ultimately hoping to increase the range of therapeutic options available to prostate and colorectal cancer patients,” added Dr Azad.  “This is all about personalised medicine; we want to be able to use the right drug for the right patient.”

The collaborative research project builds on the previous work of Hudson Institute’s Associate Professor Ron Firestein, who identified the RNA biomarker and potential benefit of BET inhibitors in pre-clinical models in his previous laboratory at Genentech Inc.

 “Ensuring the effectiveness of targeted cancer therapies not only improves survival rates but provides another option to patients who invariably develop resistance to chemotherapy,” said Associate Professor Firestein who is also co-lead investigator on the study.

Undertaken at Monash Health, the trial will recruit twenty five patients with advanced prostate or colorectal cancer and for whom other treatments options have failed. 

Dr Azad said that while there is a range of drugs that work well in prostate and colorectal cancer, patients eventually become resistant so more options are needed.

“We need to use these treatment options the smartest way we can and not use the scattergun chemotherapy approach where we give all patients the same treatment, and if 20% respond, that’s great.”

“What about the other 80% of patients for whom chemo was never going to work, who suffered unnecessary toxicity, and wasted time, effort and a lot of money?”

Dr Azad and Associate Professor Firestein are very optimistic about the potential for epigenetic therapies like BET inhibitors.

“If we can define which patients will respond best to treatment, we’re genuinely personalising cancer care,” said Dr Azad. 

“Personalised cancer care is the Holy Grail—everyone wins but most importantly the patients.”

Co-collaborators on this study include Monash University’s Professor Gail Risbridger, Associate Professor Helen Abud, colorectal surgeon Associate Professor Paul McMurrick and Cabrini’s Dr Simon Wilkins. 

Improved outcomes for patients with prostate cancer at Monash Health

Dr Arun Azad

Medical oncologist and researcher Dr Arun Azad is the recipient of a prestigious Victorian Cancer Agency Clinical Research Fellowship, announced last week by Minister for Health, the Hon Jill Hennessy MP.

The highly competitive Fellowship worth $800,000 over four years will enable to Dr Azad to characterise the effects of docetaxel chemotherapy on castration-sensitive prostate cancer.

 “In collaboration with Professor Gail Risbridger in the School of Biomedical Sciences, I will investigate whether docetaxel targets a population of ‘pre-existing’ castration-resistant cells,” said Dr Azad.

“This work may identity novel ways of making docetaxel more effective in castration-sensitive prostate cancer, paving the way for future clinical trials and better patient outcomes.”

An early-career medical oncologist and translational researcher in genitourinary malignancies, Dr Azad led cutting-edge work investigating mechanisms of therapeutic resistance and response in advanced prostate cancer patients through genomic analysis of circulating cell-free DNA (cfDNA) at the British Columbia Cancer Agency, Vancouver, Canada.

Dr Azad has played an active role in the development of 5 investigator-initiated clinical trials and been the recipient of over $1.5M in competitive funding including a prestigious CJ Martin Fellowship from the NH&MRC. His clinical and research activities have resulted in publications in high-impact journals including Journal of Clinical Oncology, European Urology and Lancet Oncology. He has also been the recipient of 15 competitive prizes and awards including Merit Awards at the American Society of Clinical Oncology Annual Scientific Meeting and Genitourinary Cancers Symposium.

Dr Azad will take up appointments at Monash Health and Monash University’s School of Clinical Sciences (SCS) later this year to focus on pre-clinical and clinical translational research in genitourinary cancers.