Haematology+Oncology_News

NEWS 6 CONFERENCE COVERAGE

H aematology & O ncology N ews • Vol. 9 • No. 1 • 2016

BCG/sunitinib combo produces high complete response rate in NMIBC

ASCO Genitourinary Cancers Symposium 2016 7–9 January 2016 • San Francisco, California The 2016 Genitourinary Cancers Symposium was a 3-day scientific and education meeting sponsored by the American Society of Clinical Oncology. On pages 6 and 7, we bring you selected reports from our coverage of the meeting, including on aspirin’s potential protective effect against fatal prostate cancer, BMI and its impact on the outcome of patients with metastatic kidney cancer, and trials that failed to boost survival of men with metastatic castration-resistant prostate cancer.

mortality rate of 4–25%, Dr Helfand noted. “Complete response to BCG at 3 months has been shown to predict future recurrence-free sta- tus. Consolidating the initial tumour response to BCG with adjunctive therapies may help improve outcomes,” he said. BCG downregulates vascular endothelial growth factor (VEGF) receptors, and sunitinib binds to VEGF receptors to prevent vascular growth. To see whether the combined therapies could act synergistically, investigators treated patients with 6-weeks of BCG induction beginning within 6 weeks of diagnostic or restaging biopsy, followed by a 2-week hiatus, then 28 days of oral sunitinib 50 mg/day. Patients with a complete response at 3 months went on to BCGmaintenance, while those with an incomplete response or recurrence at 3 months went on to a second cycle of BCG followed by sunitinib. Patients with disease progression after either treatment cycle were treated with alternative therapies at the treating clinician’s discretion. A total of 36 of 39 patients completed BCG induction and at least one dose of sunitinib, and these patients were included in the efficacy analy- sis. The safety analysis was by intention to treat, and therefore included all 39 patients. The complete response rate at 3 months after cycle one, the primary endpoint, was 73% (26 of 36 patients). Of the responders, 73% have started on BCG maintenance, 23% had no maintenance BCG and no evidence of disease at last follow-up, and the remaining 4% had cystectomies.

BY NEIL OSTERWEIL Frontline Medical News

A combination of intravesical bacillus Calmette- Guerin (BCG) followed by sunitinib produced high complete response rates in patients with high-risk, non-muscle invasive bladder cancer. In a phase II trial, 26 of 36 patients (72%) with non-muscle invasive bladder cancer (NMIBC) had a complete response following bladder installation of BCG and consolidation therapy with sunitinib (Sutent), reported Dr Alexander M. Helfand of the University of Michigan Com- prehensive Cancer Centre, Ann Arbor. “Adding sunitinib after BCG induction may result in increased rates of complete response at 3 months over those of BCG alone. The durability of response appears promising, given a 77% 2-year recurrence in high-risk patients with non-muscle invasive bladder cancer,” he said at the 2015 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology. “Certainly, this study provides the rationale to consider antiangiogenic therapy in the non- muscle invasive setting,” said Dr Jonathan E. Rosenberg of Memorial Sloan Kettering Cancer Centre, New York, the invited discussant. Induction and maintenance therapy with BCG is the mainstay of initial treatment of high-risk NMIBC. It has been associated in clinical studies with 3-month complete response rates ranging from 28% to 85%, 5-year cumulative recurrence rates from 50% to 55%, 5-year cumulative progres- sion rates of 8–20%, and a 10-year disease-specific

The results look quite good. Toxicity and tolerability, though, do make me concerned.

Of the 28% (10 patients) with residual disease at 3 months, four underwent cystectomy, two had Ta low-grade recurrences which were managed with repeat resection, and two elected a second BCG induction/sunitinib cycle. There were a total of 127 adverse events deemed to be minor among 34 patients, and 6 major adverse events occurring in 5 patients. The major events included rash on hands and feet, hand and foot syndrome, thrombocytopenia, febrile diarrhoea, sores on hands and feet, and reactivation of herpes zoster. In all, 13 patients required some delay of suni- tinib therapy, primarily due to jaundice/elevated liver enzymes or thrombocytopenia. All adverse events disappeared at the end of therapy. Of the 31 patients with an intact bladder, 2 years recurrence-free survival was 77%, and 2-year progression-free survival was 100%. Dr Rosenberg, the discussant, noted that over- all “the results look quite good. Toxicity and toler- ability, though, do make me concerned, and future trials might consider dose reduction [of sunitinib] at the start to 37.5 mg to actually increase the number of patients and time on therapy.” arm: objective response rates were 30.5% and 31.9%, respectively; median time to prostate- specific antigen progression was 8 months vs 7.6 months; uNTx reduction was 66% vs 60.6%; pain reduction was 66.6% vs 71.5%; progression-free survival was 11.8 months vs 11.1 months. The one exception was median time to first skeletal event, which was not reached in the dasatinib group and was in 31.1 months for the placebo group. Dr William Oh, chief of haematology and medical oncology at Tisch Cancer Institute and the Mount Sinai School of Medicine, New York, commented that “about two-thirds of the patients were not on bisphosphonates, which may explain why there was a trend toward a benefit in terms of (skeletal-related events)” in the dasatinib arm. DrAraujo reported there were no unexpected safety findings and no unanticipated events. Patients came off the trial for similar reasons in both arms, including disease progression and maximum clinical benefit. Adverse events re- lated to treatment included diarrhoea, fatigue, alopecia, and nausea and occurred in 18% of patients in the dasatinib arm and in 9% in the placebo arm. Grade 3–4 adverse events of inter- est included anaemia (8% vs 5.9% in placebo), neutropenia (6.2% vs 5.5%), hypocalcaemia (3.5% vs 3.1%), gastrointestinal bleeding (2.6% vs 1.3%), and pleural effusion (1.3 vs 0.4%). Dr Araujo has received research funding from Bristol-Myers Squibb, the maker of Sprycel and sponsor of the trial. Dr Oh has been consultant or adviser for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.

Dasatinib adds no survival benefit to docetaxel in mCRPC BY NASEEM S. MILLER Frontline Medical News

Texas MDAnderson Cancer Centre, Houston. In READY, 1522 patients were randomised to receive docetaxel (75 mg/m 2 , three times a week) plus prednisone and either 100 mg daily of dasatinib (762 patients), or placebo (760 patients). There were no meaningful differences in the demographics or disease characteristics of the two study arms. Patients were treated until disease progression or they had unac- ceptable toxicity. The primary endpoint of the study was overall survival. The secondary endpoints were objective response rates, time to first skeletal- related event, time to prostate-specific antigen progression, urinary N-telopeptide (uNTx) reduction, pain reduction, progression-free survival, and safety. Overall survival was 21.5 months in the dasatinib group and 21.2 months in the placebo group (hazard ratio, 0.99; P = 0.90). Comparably similar outcomes were seen in secondary endpoints for dasatinib vs placebo

A dding dasatinib to standard-of-care chem- otherapy led to a modest delay in skeletal- related events but did not improve overall survival for patients with metastatic castrate- resistant prostate cancer in the READY trial. Dasatinib, a tyrosine kinase inhibitor, showed promising results in phase I and II studies, but fell short in READY, a multina- tional randomised double-blinded, placebo- controlled study, sponsored by Bristol-Myers Squibb. With no difference in overall survival and no meaningful changes in the study’s secondary endpoints, the search continues for treat- ments for this group of patients whose cur- rent options are mostly palliative with modest improvements in survival. The observed delay in skeletal-related events with dasatinib is be- ing further investigated, said the study’s lead author, Dr  John C. Araujo of the University of

Dr Fred Saad, professor and chief of urology and director of G-U Oncology at the University of Montreal Hospital Centres, deliv- ers highlights of the past year’s prostate cancer research at the ASCO GU symposium. He point- ed out that “although there were no new drugs approved in 2015, we learned a lot about what we have available – some good and some not so good.” From a clinical perspective, and with a focus on topics that con- firm or change current practice, PracticeUpdate summarises five key topics from prostate cancer research published in 2015: screening and active sur- veillance (Part 1); local therapy (Part 2); and androgen deprivation therapy, chemotherapy in men with hormone-sensitive disease, and new options in metastatic prostate cancer (all in Part  3). This exclusive report is available on www.practiceupdate.com

PracticeUpdate is an Elsevier website.

© ASCO/Todd Buchanan 2016