11 October 2022
The European Society of Medical Oncology 2022 Conference was hosted in Paris from 9-13 September. Updates from some of the key clinical trials presented at the conference will be discussed in this blog.
Active surveillance
ENACT
Participants in the ENACT trial are on active surveillance and receive enzalutamide to assess whether it slows disease progression compared to no enzalutamide. Assessing disease progression is challenging, currently done with the use of PSA, prostate biopsies, and MRI. The investigators presented their findings on a prognostic and predictive biomarker called genomic signatures which were able to prove the benefit of using enzalutamide to delay disease progression. The disadvantage of this treatment is cost and potential side effects.
Post-prostatectomy
RADICALS-HD
This trial is investigating the optimum duration of androgen deprivation therapy (ADT) for those receiving radiation therapy after a radical prostatectomy. Participants were randomised to three groups: No ADT; 6 months of ADT and 24 months of ADT. The trial also looks at the timing of when radiation should be started after a radical prostatectomy: straight away (adjuvant) or delayed based on PSA readings (early salvage). Findings have shown that the use of 24 months of ADT improved both metastasis-free survival and the time to salvage ADT. However, 6 months of ADT (compared to none) provided only a benefit in the time to salvage ADT, without improvements in metastasis-free survival.
Metastatic disease – Hormone sensitive
ARASENS
In those with metastatic hormone sensitive prostate cancer daralutamide, ADT and docetaxel has been shown to reduce mortality by 32.5% compared to placebo, ADT, and docetaxel. Long term follow up has shown that quality of life is maintained with minimal side effects from treatment (include effects on the heart). This is has now become the standard of treatment is most centres.
PEACE-1
A combination of ADT, docetaxel, abiraterone and prednisone improves overall survival in those with metastatic castrate sensitive prostate cancer (these patients are sensitive to the effects of ADT and have not developed resistance yet). At the conference the investigators reported that there is also improved radiological progression free survival in patients who have cancer that’s spread to the liver. The most common type of prostate cancer seen under the microscope is called adenocarcinoma. There are rarer variants known as pure neuroendocrine or neuroendocrine differentiated. These require specialised staining techniques to be detected known as systemic immunohistochemistry. In their study 14% of participants had adenocarcinoma with neuroendocrine differentiation and 0.5% had pure neuroendocrine differentiated cancer. This was too small a sample size to draw any conclusions on treatment-related benefit in this group but the investigators recommend that future studies should include this subset of patients.
Metastatic disease – castrate resistant
CYPIDES
This trial looks at a new androgen deprivation therapy, simply called ODM-208. It blocks the testosterone production pathway in the adrenal gland. It is used in patients with metastatic castrate resistant prostate cancer (mCRCP) who have trialled 2 or more ADTs previously as well as chemotherapy, such as docetaxel, and still have a rising PSA and is symptomatic. As discussed in previous blogs prostate cancer is able to alter the parts of the body where drugs bind to cells thereby creating resistance to treatment. ODM-208 has shown benefit for those who have an androgen receptor ligand binding domain mutation and able to overcome this resistance mechanism. More than 50% of participants showed a PSA decline of 50% from baseline.
CABASTY
Cabazitaxel is a chemotherapy drug used in the treatment of mCRPC. One of its main side effects is a low white cell count (neutropenia), the immune fighter cells of the body. This means that patients are prone to infection and high fever particularly in the ageing population (>75 years). The investigators of this trial wanted to see whether there would be less treatment related side effect if a lower dose of this drug was given every two weeks instead of every three weeks. Study objectives were met, and older, less medically fit patients had fewer side effects with the same benefits on overall survival, radiological progression free survival and PSA response compared to the 3 weekly regime.
IMPROVE
Metformin is a drug used in the treatment of insulin independent diabetes mellitus (Type2) to lower blood glucose levels. In this randomized clinical trial participants with mCRPC and progressive disease were randomised to received enzalutamide (ADT) or enzalutamide with metformin. Previous studies have demonstrated that metformin has effects on tumour growth with reduction in PSA in non-diabetic patients. At 15 months the combination of enzalutamide and metformin have not shown a benefit for overall survival. In overweight and obese men, however, there was improved event-free survival and time to PSA progression. Longer follow up is required with a larger number of participants.
SPLASH
PSMA can be used to make a diagnosis of metastatic prostate cancer, but it can also be combined with Lutetium to target metastatic cancer deposits as a form of treatment. In this trial, participants with mCRPC who have trialled abiraterone or enzalutamide (without chemotherapy) and their cancer has progressed, received 177Lu-PSMA I&T. Preliminary findings show a favourable radiological progression free survival with minimal side effects.
In conclusion the trials, which are all in varying phases of their investigations, have demonstrated some very positive findings for prostate cancer patients with different disease stages. It will be interesting to track the long term follow up results when they are reported in the near future.
About the Author
Kalli Spencer
MBBCh, FC Urol (SA), MMed (Urol), Dip.Couns (AIPC)
Kalli is an internationally renowned Urological Surgeon, specialising in oncology and robotic surgery. He trained and worked in South Africa, before relocating to Australia where he has worked at Macquarie University Hospital and Westmead Hospital. His passion for what he does extends beyond the operating room, through public health advocacy, education and community awareness of men’s health, cancer and sexuality.
Kalli has been involved with the Prostate Cancer Foundation of Australia for many years, advocating for improved cancer care and facilitating community prostate cancer support groups.
