PracticeUpdate: Haematology & Oncology

EDITOR’S PICKS 8

Atezolizumab for advanced urothelial carcinoma, adjuvant sunitinib for high-risk RCC after nephrectomy and 10-year outcomes for localised prostate cancer

Atezolizumab as first-line in cisplatin-ineligible patients with advanced urothelial carcinoma C isplatin-based chemotherapy has been the mainstay in the treatment of metastatic urothelial cancer.

Drs Rajesh Nair and Homi Sagar share their top three recent clinical trials – S-TRAC, ProtecT and IMvigor210 – and their impact on patients with bladder, renal and prostate cancers.

diarrhoea (12%), and pruritis (8%). There was one treatment-associated mortality due to sepsis, and treatment was discontinued in 8%. Reassuringly, nephrotoxicity has been reportedly low in this cohort. This is a critical study; it reveals similar response rates to previous studies involving checkpoint inhibitors. Immunotherapy appears to be much easier to tolerate than chemotherapy, and this is especially important for elderly patients or those with significant renal impairment. However, with less than 30% of patients responding to the drug, future studies are essential in the predictive biomarkers field to determine response. The future also necessitates studies evaluating drug sequencing, combination therapy with chemotherapy, PD-1 inhibitors (eg, pembrolizumab), and the role of neoadjuvant therapy in muscle invasive disease. We remain at the tip of a very exciting iceberg.

Unfortunately, over 60% of patients are ineligible to receive this treatment. Reasons include poor performance status, impaired renal function or heart failure. Atezolizumab, a class of checkpoint inhibitor immunotherapy, targets the protein PD-L1 found on tumour cells. PD-L1 binding to PD-1 on immune cells supresses the host immune response. Balar and colleagues report the promising results of a multicentre, non-randomised single-arm, phase 2 study of atezolizumab in a cohort of patients with locally advanced or metastatic urothelial carcinoma not suitable for cisplatin-based chemotherapy. For the 119 patients who received one or more doses of atezolizumab, the overall response rate was 23%; complete response rate was 9% and 70% of responses were on-going. Median overall survival was 15.9 months. Treatment related adverse events included fatigue (30%),

Rajesh Nair, FRCS (Urol), FEBU, MSc is a UK-trained urological surgeon undergoing advanced fellowship training in robotics and uro-oncology at the Royal Melbourne Hospital.

Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet 2016 Dec 7; [Epub ahead of print]. AV Balar, MD Galsky, JE Rosenberg, et al; IMvigor210 Study Group. Take-home message • This was a multicentre, single-arm, phase 2 study evaluating the safety and efficacy of first- line atezolizumab monotherapy (1200 mg fixed dose) in 123 cisplatin-ineligible patients with advanced urothelial carcinoma. The objective response rate was 23%. Tumour mutation load was associated with response. Median overall survival was 15.9 months. • Results indicated that atezolizumab is active in patients with advanced, untreated cisplatin- ineligible urothelial carcinoma.

Homayoun (Homi) Zargar, MD, FRACS is a urological surgeon with fellowship training in uro-oncology, and advanced laparoscopic and robotic surgery. He is Consultant Urologist at the Royal Melbourne Hospital and Senior Clinical Lecturer, Department of Surgery, University of Melbourne.

PRACTICEUPDATE HAEMATOLOGY & ONCOLOGY