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Promising immunotherapy agents in renal and bladder cancers

Promising agents are awaited, particularly in immunotherapy for advanced kidney and bladder cancers while hormonal treatment still remains a major player in prostate cancer.

At the Game-Changing segment of Plenary Session 3, the key developments in the medical treatment of renal, urothelial and prostate cancers were taken up by Professors Marc-Oliver Grimm (DE), who discussed kidney and bladder therapies, and Nicolas Mottet (FR), who examined the promising options in prostate cancer.

Grimm examined the changes in medical treatment, including a few caveats in management that urologists need to know, and explored future directions such as combination and adjuvant treatments in renal cell carcinoma (RCC). He prefaced his talk with a brief look at targeting CTLA-4 and PD-1 pathways with monoclonal antibodies, and mentioned the development of approval of ipilimumab for melanoma that began in 2011 (in the USA and Europe).

Grimm discussed the outcomes of major studies such as KEYNOTE-045 which compared pembrolizumab with chemotherapy (paclitaxel + docetaxel + vinflunine) in platinum refractory disease (urothelial carcinoma) and noted the increased gains in overall and progression-free survival with pembrolizumab.

In advanced or metastatic urothelial cancer, Grimm also mentioned EMA approvals such as the antibody agent pembrolizumab in first-line therapy for cisplatin ineligible patients and nivolumab and pembrolizumab in second-line therapy after platin –based chemotherapy.

In terms of RCC, Grimm mentioned CheckMate 214, which examined first-line nivolumab plus ipilimumab (nivo + ipi) versus sunitinib for treatment-naïve advanced or metastatic RCC patients. For nivo + ipi the overall response rate was 42% compared to 27% for sunitinib, with a progression-free survival of 11.6 months for nivo + ipi versus 8.4 months for sunitinib.

“Future directions indicate combination therapy with PD-1/PD-L1 inhibitors in RCC with nivolumab plus ipilimumab and PD1/PD-L1 inhibitors plus VEGFR-TKI. For urothelial cancer we have tremilimumab plus durvalumab/nivolumab plus ipilimumab… while adjuvant treatment is PD-1/PD-L1 plus combination,” he added.

Grimm also noted that ongoing game-changing trials in RCC in Phase 3 adjuvant setting include IMmotion 010, CheckMate 914, and PROSPER RCC (neo-adjuvant), while in Phase 3 first-line metastatic RCC studies include CheckMate 214. IMmotion 151, KEYNOTE-426, Javelin Renal 101, NCT02811861 and CheckMate 9ER.

Mottet, meanwhile, provided an overview of androgen deprivation treatment of locally advanced prostate cancer (PCa), issues in intermittent therapy, the role of upfront aberaterone in M1 patients, and the standard of care (SOC) for newly diagnosed M1 disease.  He said there is strong evidence for the recommendation to offer castration combined with chemotherapy (docetaxel) to all patients whose first presentation is M1 disease and who are fit enough for docetaxel. There is also strong evidence for offering castration combined with abiraterone acetate plus prednisone to patients whose first presentation is M1 disease and who are fit enough for the regime.

“Hormonal treatment remains a major player and a key driver… however questions remain with regard to combination with salvage EBRT. And in M1 disease there is a revolution leading to improved survival,” he said.

Article by Joel Vega

Promising immunotherapy agents in renal and bladder cancers