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Best of JCO™ 2018: Genitourinary Cancer Edition

Introduction

The content compiled here represents some of the most-accessed original research from recently published Journal of Clinical Oncology articles across a range of topics including prostate and bladder cancer.

Postdiagnosis Statin Use and Mortality in Danish Patients With Prostate Cancer

A nationwide cohort study of data from Danish registries was conducted to examine whether statin therapy was associated with reduced mortality in patients with prostate cancer.

Summary

A growing body of evidence indicates that, in patients with prostate cancer, statins may slow disease progression and reduce mortality.

Data from 31,790 patients with incident prostate adenocarcinoma, diagnosed between 1998 and 2011 in Denmark, were analysed.

After a median follow-up of 2.8 years, statin use was associated with a 15–20% reduction in prostate cancer and all-cause mortality.

Prostate cancer mortality was lower in patients who underwent endocrine treatment or radical prostatectomy compared with patients in the overall analysis.

Sensitivity analyses found that dose and type of statin, duration of exposure, clinical stage, Gleason score and pre-diagnosis use did not affect the benefit associated with statin therapy.

Larsen SB et al. J Clin Oncol 2017; 35(29): 3290-3297. doi:10.1200/JCO.2016.71.8981

Cabazitaxel Versus Docetaxel As First-Line Therapy for Patients With Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase III Trial-FIRSTANA

This was the first head-to-head comparison of two therapies (cabazitaxel and docetaxel) that are known to prolong survival in the treatment of metastatic, castration-resistant prostate cancer (mCRPC).

Summary

In patients with breast cancer, the use of anthracycline and taxanes in the adjuvant setting is standard therapy. However, it was found that the benefit of anthracyclines is largely associated with patients who have TOP2A-altered tumours.

In this phase 3, open-label trial patients with early TOP2A-normal breast cancer were randomly assigned to receive 6 cycles of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks (DC) or 3 cycles of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) followed by three cycles of docetaxel (100 mg/m2; EC-D). The primary endpoint was disease-free survival (DFS) after 5 years of follow-up.

There was no overall outcome benefit from the anthracycline-containing adjuvant regimen, compared with DC of similar duration in patients with TOP2A-normal tumours. Five-year disease free survival rates were 87.9% (95% CI, 85.6% to 89.8%) for the EC-D group and 88.3% (95% CI, 86.1% to 90.1%) for the DC group.

Patients receiving EC-D had more Grade 3 or 4 febrile neutropenia, higher grade nonhaematologic toxicity, and peripheral neuropathy, compared with patients receiving DC.

Menopausal status was statistically significant for DFS, but not for overall survival. Postmenopausal patients had a better outcome benefit with EC-D, whereas premenopausal women were associated with outcome benefit from DC.

Oudard S et al. J Clin Oncol 2017; 35(28): 3189-3197. doi:10.1200/JCO.2016.72.1068

Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m2) and the Currently Approved Dose (25 mg/m2) in Postdocetaxel Patients With Metastatic Castration-Resistant Prostate Cancer-PROSELICA

The PROSELICA study investigated whether cabazitaxel 20 mg/m2 was noninferior to cabazitaxel 25 mg/m2 in terms of overall survival (OS) in post-docetaxel patients with metastatic castration-resistant prostate cancer (mCRPC).

Summary

Based on early clinical studies, the 20 and 25 mg/m2 doses of cabazitaxel were recommended for phase 2 and 3 studies, with data suggesting that the lower dose may be associated with an improved safety profile.

In this phase 3 study, post-docetaxel patients with mCRPC were randomized to cabazitaxel 20 or 25 mg/m2; the primary end point was OS, and the secondary end points included progression-free survival (PFS), tumour, prostate-specific antigen (PSA) and pain response and progression and safety.

There was no significant difference in OS between cabazitaxel 20 and 25 mg/m2 (median OS 13.4 vs 14.5 months), and noninferiority was confirmed.

Some secondary efficacy endpoints favoured cabazitaxel 25 mg/m2, with significantly greater improvements versus cabazitaxel 20 mg/m2 for PSA response and time to PSA progression, while PFS and rates of tumour, PSA and pain progression were similar.

There were fewer grade 3 or 4 treatment-emergent adverse events with cabazitaxel 20 than with cabazitaxel 25 mg/m2 (39.7% vs 54.5%).

This study suggests that similar clinical benefits can be achieved with cabazitaxel 20 and 25 mg/m2, and that dose reductions may be used when required without adversely affecting survival outcomes.

Eisenberger M et al. J Clin Oncol 2017; 35(28): 3198-3206. doi:10.1200/JCO.2016.72.1076


Effect of comorbidity on prostate cancer-specific mortality: a prospective observational Study

This Swedish population-based study assessed the effect of comorbidities on prostate cancer-specific mortality.

Summary

Evidence for the effect of comorbidities on cancer-specific and other-cause mortality in patients with prostate cancer is conflicting.

This observational study hypothesised that prostate cancer-specific mortality is not affected by comorbidity after accounting for patient and tumour characteristics and treatment type.

In 118,543 men with prostate cancer (median follow-up 8.3 years), comorbidity was associated with increased prostate cancer-specific and other-cause mortality in the complete unadjusted data set.

After adjusting for patient and tumour characteristics and treatment type, the effect of comorbidity on prostate cancer-specific mortality was not statistically significant, but was maintained for other-cause mortality.

This study suggests that comorbidity affects other-cause mortality but not prostate cancer-specific mortality in patients with prostate cancer.

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Rajan P et al. J Clin Oncol 2017; 35(31): 3566-3574. doi:10.1200/JCO.2016.70.7794

Propensity Score Analysis of Radical Cystectomy Versus Bladder-Sparing Trimodal Therapy in the Setting of a Multidisciplinary Bladder Cancer Clinic

This retrospective study compared clinical outcomes among patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy (RC) versus bladder-sparing trimodal therapy (TMT).

Summary

While RC has been the traditional therapy for patients with MIBC, bladder-sparing strategies have emerged as valid treatment options over the past decades.

Bladder-sparing TMT (which consists of transurethral bladder tumour resection, chemotherapy for radiation sensitisation and external beam radiotherapy) has been associated with excellent outcomes and preserved bladder function in non-comparative studies of patients with MIBC, but has not been assessed in randomised trials.

Among 112 retrospectively identified patients referred to a multidisciplinary bladder cancer clinic between April 2008 and December 2012 (median follow-up 4.51 years), there were no significant differences in median overall survival or the 5-year disease-specific survival rate for TMT- versus RC-treated patients.

Salvage cystectomy was required in 10.7% of patients in the TMT group, but no cystectomy was required for bladder toxicity.

Eligible patients should be offered to opportunity to discuss TMT as a treatment option before selection of therapy for MIBC.

Kulkarni GS et al. J Clin Oncol 2017; 35(20): 2299-2305. doi:10.1200/JCO.2016.69.2327

Risk of Cardiovascular Ischemic Events After Surgical Castration and Gonadotropin-Releasing Hormone Agonist Therapy for Prostate Cancer: A Nationwide Cohort Study

This study assessed whether cardiovascular risk in patients with prostate cancer varies between those who undergo surgical castration and those who receive gonadotropin-releasing hormone agonist (GnRHa) therapy.

Summary

Emerging evidence indicates that androgen deprivation therapy (ADT) with GnRHa or surgical castration (orchiectomy) may be linked to increased risk of cardiovascular ischaemic events; however, there are insufficient data to determine which ADT is associated with the highest risk.

In this retrospective analysis of the Taiwan National Health Insurance Research Databases (n=14,715; median follow-up 3.3 years), the risk of cardiovascular ischaemic events with orchiectomy was similar to that with GnRHa therapy.

Orchiectomy was associated with increased risk of cardiovascular ischaemic events within 1.5 years in patients who were aged ≥65 years, had hypertension, had a Charlson comorbidity index score ≥3, or had a history of myocardial infarction, ischaemic stroke or coronary heart disease.

This study indicates that GnRHa therapy does not increase cardiovascular risk when compared with orchiectomy in patients with prostate cancer.

Chen DY et al. J Clin Oncol 2017; 35(32): 3697-3705. doi:10.1200/JCO.2016.71.4204


Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study

This study assessed the efficacy and safety of recombinant adenovirus interferon-α with Syn3 (rAd–IFNα/Syn3) in patients with high-grade bacillus Calmette-Guerin (BCG)-refractory or relapsed non-muscle-invasive bladder cancer (NMIBC).

Summary

Finding an effective alternative to radical cystectomy for patients with high-grade BCG-refractory NMIBC is an important unmet clinical need.

This open-label, multicentre, phase 2 study investigated the efficacy and safety of intravesical rAd–IFNα/Syn3 1 × 1011 viral particles (vp)/mL (n=21) or 3 × 1011 vp/mL (n=19) in patients with high-grade BCG-refractory NMIBC.

Twelve months after initial treatment with rAd–IFNα/Syn3, 14 out of 40 patients (35%) were free of high-grade NMIBC recurrence; the high-grade recurrence-free survival rate was similar in both dose groups.

During long-term follow-up, two patients experienced high-grade recurrence at 21 and 28 months, respectively.

The most common drug-related adverse events (AEs) were micturition urgency (40%), dysuria (40%), fatigue (32.5%), pollakiuria (28%), haematuria (25%) and nocturia (25%); 19 grade 3 AEs were reported in nine patients, and no grade 4 or 5 AEs occurred.

In patients with high-grade BCG-refractory NMBIC who were unable or unwilling to undergo radical cystectomy, intravesical administration of rAd–IFNα/Syn3 demonstrated promising efficacy and was well tolerated.

Shore ND et al. J Clin Oncol 2017; 35(30): 3410-3416. doi:10.1200/JCO.2017.72.3064

ASCO® and the American Society of Clinical Oncology® are registered trademarks of the American Society of Clinical Oncology, Inc. Used with permission. The ideas and opinions expressed in the Journal of Clinical Oncology (JCO) do not necessarily reflect those of the American Society of Clinical Oncology or Springer Healthcare. The mention of any product, service, or therapy in this publication should not be construed as an endorsement of the products mentioned. It is the responsibility of the treating physician or other health-care provider, relying on independent experience and knowledge of the patient, to determine the appropriate treatment for the patient. Viewers are advised to check the appropriate medical literature and the product information currently provided by the manufacture for each product or therapy to be administered to verify the dosage, method, and duration of administration, or contraindications. The American Society of Clinical Oncology and Springer Healthcare assume no responsibility for any injury or damage to persons or property arising out of or related to any use of the material contained in this publication, or to any errors or omissions.

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