PracticeUpdate: Haematology & Oncology

EDITOR’S PICKS 6

Higher rates of long-term overall survival with radiation and antiandrogen therapy for recurrent prostate cancer

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.

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.

T raditional standard of care for patients who exhibit biochemical recurrence (elevated and rising prostate-spe- cific antigen [PSA] level) and therefore recurrent prostate cancer following radical prostatectomy is salvage radiotherapy. Shi- pley and colleagues evaluate the impact of adding an antiandrogen on disease-specific and overall survival. This double-blind pla- cebo controlled study assessed 760 men who had undergone radical prostatectomy with pelvic lymphadenectomy with patho- logical T-stage, T2 or T3 and N0 prostate adenocarcinoma. All patients demonstrated evidence of biochemical recurrence as defined by a PSA of 0.2–4.0 ng/mL and were randomised to salvage radiation

a number of caveats one must consider when evaluating the data presented. Most concomitant androgen deprivation regi- mens focus on using a luteinising hormone releasing hormone analogue. Certainly, most comparative ongoing salvage radiation trials use this and not bicalutamide, which here is delivered at the 150 mg once daily. This is far higher than the recommended dosage of 50 mg once daily. In addition, the timing of adjuvant radiation in this cohort of trial patients appears to be significantly delayed when compared to the current standard, which is when PSA reaches 0.2–0.5 ng/dL. Certainly, this patient cohort is an impor- tant one for urologists and oncologists alike. While this study certainly is informative, we

therapy alone or in combination with bical- utamide monotherapy (150 mg/day) for 2 years. With a median follow-up of 13 years, over- all survival at 12 years was 76.3% in the bicalutamide group vs 71.3% in the pla- cebo group. Death from prostate cancer was 5.8% vs 13.4% in the bicalutamide and pla- cebo groups, respectively. Finally incidence of metastatic disease at 12 years was 14.5% and 23% in the bicalutamide and metastatic disease groups, respectively. This study is unique in demonstrating the addition of antiandrogen therapy to sal- vage radiation therapy reduced overall and cancer-specific survival, and progression to metastatic disease. However, there are

Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275) T raditional treatment for metastatic bladder cancer is cisplatin-based chemotherapy. Unfortunately, due patients are ineligible to receive this treat- ment. Their prognosis is poor. found on tumour cells binding to PD-1 on immune cells suppressing the host immune response.

Nivolumab, is a humanised IgG4 PD-1 immune checkpoint inhibitor. This form of immunotherapy targets the protein PD-L1

to comorbidities, deteriorating renal func- tion or cardiac impairment, over 60% of

Sharma et al report the promising results of a multicentre, phase II, single-arm study examining nivolumab in patients with metastatic or locally advanced urothelial carcinoma, whose disease progressed or recurred despite previous platinum-based chemotherapy. Patients received nivolumab 3 mg/kg intravenously every 2 weeks until disease progression, clinical deteriora- tion or as a result of toxicity. Of the 265 patients evaluated, median follow-up was 7 months, with an overall objective response rate of 19.6%. Interestingly, this study goes one step further. PD-L1 expression was recorded from tissue obtained (>5% and 1%). Of those who expressed >5% and >1% PD-L1 expression, response to nivoul- mab was 28.4% and 23.8%, respectively.

Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial Lancet Oncol 2017 Jan 25;[EPub Ahead of Print], P Sharma, M Retz, A Siefker-Radtke, et al Take-home message • In this single-arm study, 265 patients with metastatic or surgically unresectable advanced urothelial carcinoma were given nivolumab, a PD-1 inhibitor. A confirmed objective response was achieved in 28.4% (23/81), 23.8% (29/122), and 16.1% (23/143) of patients with PD-L1 expression ≥ 5%, ≥ 1%, and <1%, respectively. Overall survival was 7 months. • Nivolumab treatment has an acceptable safety profile and is clinically beneficial, but improved outcomes did not correlate with PD-L1 expression in patients with unresectable advanced urothelial carcinoma.

PRACTICEUPDATE HAEMATOLOGY & ONCOLOGY