PracticeUpdate: Haematology & Oncology

EDITOR’S PICKS 9

Adjuvant sunitinib increases disease-free survival in patients with high-risk RCC after nephrectomy T he S-TRAC trial reported by Ravaud and colleagues is a phase 3 trial of the VEGF pathway inhibitor sunitinib

Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy N Engl J Med 2016;375:2246-2254. A Ravaud, RJ Motzer, HS Pandha, et al; S-TRAC Investigators Take-home message • This double-blind, phase 3 trial included 615 patients with locoregional, high-risk clear cell renal cell carcinoma who were randomised to receive sunitinib or placebo. Patients receiving sunitinib exhibited a significantly longer median disease-free survival compared with patients receiving placebo (6.8 vs 5.6 years; P = 0.03). Dose reductions, interruptions, and discontinuations were more frequent in patients receiving sunitinib. The occurrence of serious adverse events was similar between the groups, with no deaths attributed to treatment. • The study results showed that sunitinib significantly lengthened disease-free survival in patients with locoregional clear cell RCC at high risk for tumour recurrence following nephrectomy, although this benefit was accompanied by increased adverse events. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer N Engl J Med 2016;375:1415-1424. FC Hamdy, JL Donovan, JA Lane, et al; ProtecT Study Group. Take-home message • This was a multicentre, randomised trial including 1643 men with newly diagnosed localised prostate cancer, which was designed to compare three potential treatment strategies: active monitoring, radical prostatectomy, and external-beam radiotherapy. At a median follow- up of 10 years, there were only 17 prostate cancer-specific deaths in the three treatment groups combined (prostate cancer-specific survival of at least 98.8% in all groups at 10 years). There was no significant difference in overall survival among the patients whether treated with observation, prostatectomy, or external-beam radiotherapy. Metastatic disease was also rare irrespective of treatment arm (62 of 1643 patients) but was more common in the observation arm compared with either the upfront radiation or surgery arms (33 vs 13 vs 16 events for observation, surgery, and radiation groups, respectively). • The authors concluded that, while prostate cancer-specific mortality rates remained low despite the treatment strategy employed, surgery and radiotherapy resulted in lower incidences of disease progression and metastases.

survival data was not complete. Adverse events were responsible for dose reductions in 34.3% of the sunitinib group compared with only 2% of placebo patients. There were more treatment interruptions (46.4% vs 13.2%) as well as more treatment discontinuations (28.1% vs 5.6%) in the sunitinib group. Despite a similar number of serious adverse events, there were significantly more frequent grade 3 adverse events in the sunitinib arm (48.4% vs 12.1%). This is a positive trial promoting the use of adjuvant therapy. However, it is important to highlight that more than 50% of the patients in the placebo arm did not experience any recurrence. Furthermore, similar studies, including the ASSURE trial, have demonstrated no differences in disease free or overall survival in a similar setting. A number of comparable trials are underway and where there currently remains equipoise in outcomes and opinion, the future will tip the scales one way or another. It is important to recognise that modern day active surveillance regimens incorporate serial PSA testing, digital rectal examination, serial prostate biopsies or imaging. The trial protocol mandated only rectal examination and PSA testing. While the conclusions do allow for additional support using conservative management for select patients, however, one must not confuse modern day active surveillance and active monitoring used in the trial design. The vast majority of patients in the trial exhibited low-risk disease; many of these patients would be considered for modern day active surveillance. Today, active treatment would be reserved for intermediate and higher risk prostate cancer. It is important to note that although radical treatment is effective in reducing disease progression and metastases, based on the data presented, this did not translate into improved survival.

for adjuvant treatment of high-risk renal cell carcinoma after nephrectomy. It is one of the first studies demonstrating the benefit of adjuvant therapy in patients with renal cell carcinoma. Although one should be cautious when interpreting the results, the investigators have allowed for an optimistic view when managing the disease in the higher risk patient population, where recurrence rates after nephrectomy are approximately 50%. A total of 615 patients with high-risk clear cell renal cell carcinoma following nephrectomy were randomised to either placebo or full dose 50 mg of sunitinib for 4 weeks on, 2 weeks off for 1 year or until disease recurrence. Patients with suspected metastases were excluded from the study. The primary endpoint was met with a significantly longer disease-free survival of 6.8 years with sunitinib compared with 5.6 years with placebo. At 5 years, 59.3% were disease-free in the sunitinib group versus 51.3% in the placebo group. Overall monitoring, surgery or radiotherapy for localised PSA-detected prostate cancer. Many authors have failed to recruit to similar studies in the past. Both oncological and functional outcomes of patients were evaluated. A total of 545 patients were randomised to active monitoring, 553 to radical prostatectomy and 545 to radiotherapy. At a median follow-up of 10 years, there were no significant differences in prostate cancer- specific or overall survival between groups. Of note, there was a notable increase in disease progression and metastasis in men managed with active monitoring. With respect to functional outcomes, worse urinary continence and erectile function was observed following surgery, whereas voiding and bowel-related symptoms were worse after radiotherapy. There are a number of caveats one must consider when evaluating the data presented. The ProtecT authors assumed a prostate cancer mortality of 15% when powering the study. As the trial progressed,

Positive 10-year outcomes for localised prostate cancer across treatment strategies T he ProtecT trial is a highly commendable effort evaluating 10-year outcomes following active this figure was however significantly lower at 1%. Although the result is huge, conclusions are drawn from very few events (17 deaths).

VOL. 2 • NO. 1 • 2017