In his lecture “Early hormonal manipulation in M0 CRPC”, Prof. Dr. Karim Fizazi (FR) defined non-metastatic castration-resistant prostate cancer (M0 CRPC) as a male patient with prostate cancer who previously had local treatment often, and had prostate-specific antigen (PSA) relapse and then received androgen-deprivation therapy (ADT) or ADT with primary local treatment. He is progressing by PSA while on ADT, and his testosterone is at castrated levels. There are no detectable metastases using conventional imaging such as bone scan or CT scan.

“M0 CRPC is a rare situation,” said Prof. Fizazi. “If next-generation imaging is used, M0 CRPC becomes even rarer.”

He stated that two agents, Enzalutamide and Apalutamide, contributed to the “clear and meaningful improvement of metastasis-free survival (MFS).” The toxicity is acceptable; however, there are some issues such as cognitive impairment,  cardiovascular toxicity, and fractures. “We need more information to know which agent is better in terms of overall survival (OS). Also, cost is a factor to be considered.”

According to Prof. Fizazi, data on darolutamide is coming soon. He cited a press release published on 24 October 2018 that Orion and Bayer have completed the ARAMIS (Androgen Receptor inhibiting Agent for MetastatIc-free Survival) Phase III trial of darolutamide in patients with M0 CRPC which stated that the primary endpoint of metastasis-free survival was met.

CARMENA trial
“Cytoreductive nephrectomy (CN) should no longer be considered as the standard of care in metastatic renal cell carcinoma (mRCC), at least when medical treatment is required,” stated Prof. Arnaud Méjean (FR) during his presentation on the Clinical Trial to Assess the Importance of Nephrectomy (CARMENA) trial.

The findings of the CARMENA trial concluded that sunitinib alone was not inferior to cytoreductive nephrectomy followed by sunitinib in patients with metastatic mRCC who were classified as having intermediate- or poor-risk patients.

Following Prof. Méjean’s presentation, discussant Prof. Axel Bex (NL) shared that poor-risk patients should not undergo CN if symptomatic, and mentioned that both CARMENA and SURTIME studies demonstrate that intermediate-risk patients, who require systemic therapy, benefit from immediate medical therapy. “However, the question is still out there,” said Prof. Bex. “Should CN be performed at a later stage in all patients except those who progress (SURTIME) or only when necessary (CARMENA)?”

POUT trial
Dr. Alison Birtle (GB) announced the successor trial to PeriOperative chemotherapy or sUrveillance in upper Tract urothelial cancer, also known as POUT (CRUK/11/027; NCT01993979, NIHR portfolio) which is POUT 2: Chemotherapy with or without immunotherapy following nephron-ureterectomy for upper tract urothelial cancer.

The rationale for POUT 2 is that high incidence of microsatellite instability in Upper Urinary Tract Urothelial Carcinoma (UTUC) may predispose to immunotherapy sensitivity; and that it has proven feasible to combine immunotherapy with chemotherapy.

The primary endpoint is disease-free survival and secondary endpoints include overall survival, safety and tolerability, and patient-reported outcomes.

Discussant Dr. Evanguelos Xylinas (FR) stated, “The opportunity to address clinical trials in the selected UTUC population is rationale/feasible (thanks to POUT), supported by different underlying biology in UTUC compared to urothelial carcinoma of the bladder (UCB).

About POUT
The POUT study won the first prize for Best Abstract in Oncology at the 33rd Annual EAU Congress held in Denmark early this year. The study concluded that adjuvant platinum-based chemotherapy should be considered as a new standard of care; it is tolerable for patients and improved MFS in UTUC. Recruitment to the POUT trial was terminated early because of efficacy was met in favour of chemotherapy. Read more about POUT here.

For more information and to access webcasts and abstracts, check out the EMUC18 Resource Centre.

The post Progress updates of notable trials at EMUC18: What you need to know appeared first on EMUC25.

“The POUT trial is the first randomised trial in this niche area. It has shown an absolute improvement of 16% (95% CI:2-30%) in disease free survival (DFS) at two years in favour of chemotherapy and a similar benefit for metastasis-free survival (MFS). Data collection for overall survival is ongoing. We have had retrospective data in this area; now we have robust data to guide treatment and to change practice,” said Dr. Birtle.

The study won the first prize for Best Abstract in Oncology at the 33rd Annual EAU Congress held in Copenhagen, Denmark early this year.

The POUT study

The POUT trial was coordinated by the Clinical Trials and Statistics Unit at The Institute of Cancer Research (ICR-CTSU) and between May 2012 and November 2017, 261 patients were randomised to receive either chemotherapy (131) or surveillance (129) at 57 hospitals across the UK. POUT examined the role of post nephro-ureterectomy (NU) treatment for UTUC and whether adjuvant chemotherapy improves DFS for patients with histologically confirmed TCC pT2-pT4 pN0-3 M0 or pTany N1-3 M0, WHO PS 0-1 who were fit to receive chemotherapy.

The POUT findings concluded that adjuvant platinum based chemotherapy should be considered as a new standard of care; it is tolerable for patients and improved MFS in UTUC. Recruitment to the POUT trial was terminated early because of efficacy was met in favour of chemotherapy; follow up for overall survival continues.

Potential and possibilities

In terms of possible new breakthroughs in the coming years, Dr. Birtle anticipates that there could be data on adjuvant treatment with checkpoint inhibitors: “We will have data on adjuvant treatment with checkpoint inhibitors in bladder cancer –  the studies are not powered sufficiently for the UTUC cohorts as these were added post hoc so they won’t truly answer how effective check point inhibitors are in UTUC adjuvantly. Similarly, studies in metastatic urothelial cancer will read out, comparing immuno-oncology (IO) versus chemotherapy versus a combination.” Dr. Birtle is currently working on a successor trial to POUT.

Working together

According to Dr. Birtle, the lack of access to data is crucial for researchers since it leads to bottlenecks and delays the progress of current trials, which in turn affects the speed of offering curative therapies to cancer patients. She added, “The barriers among countries (even pre-Brexit) makes true collaborations challenging. We don’t want competing trials, we want to run studies together across countries to give us data to move onto the next trial. Pooling our individual biobanks so that we can mine the wealth of translational work is vital.”

“POUT is a triumph of UK collaboration. 71 UK sites were opened and 57 recruited at least one patient.  We need to make sure that other countries can join together and reduce bureaucracy so that we can recruit to important trials quickly and improve options for patients. We should all view research as the core business as it improves what we can do for patients. It should never be seen as an optional extra.”

On multidisciplinary team (MDT) work, she commented that forums and events like the EMUC significantly contributes to a more effective network among cancer specialists. “Meetings like this are so important – not just to keep up to date but to hear what is going on, what the next stages might be, and to network with colleagues so that we can join in cutting-edge research at an early stage.”

EMUC as a platform

At EMUC18, the POUT update will be taken up during the session “New trials update: What we need to know.” Also to be presented during this session are key updates on the CARMENA, STAMPEDE, PRECISION and HORRAD trials. Biostatistician Laurence Collette (BE), surgical oncologist Ganesh Palapattu (US), and radiation oncologist Alberto Bossi (FR) will chair the session which will be held on Saturday, 10 November.

Annually held as a platform for scientific updates and professional networking for urological cancers experts, EMUC focuses on improving MDT work and is organised by three of Europe’s frontline professional associations – the European Society for Medical Oncology (ESMO), the European Association of Urology (EAU), and the European SocieTy for Radiotherapy & Oncology (ESTRO).

EMUC18’s Scientific Programme will address clinical and research issues with the interactive sessions to be led by opinion leaders, expert lecturers and speakers from across Europe and North America. From decision-making dilemmas to future prospects in drug development, participants will not only contribute to the discussion through direct voting but can also join workshops, special courses, hands-on training and other specialist forums.

Want to know more about EMUC18? For additional information on the Scientific Programme, Venue and Registration, visit the meeting website.

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