EMUC18: Updates on notable trials

10 November 2018

Developments of notable trials were announced today during Plenary Session 06 New trials update: What we need to know which was chaired by Dr. Laurence Colette (BE), Dr. Ganesh Palapattu (US), Dr. Stephen Boorjian (US) and Dr. Alberto Bossi (FR).

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.

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