In This Article
- Abiraterone and Metabolic Syndrome
- Obesity and Survival in Metastatic Renal-Cell Carcinoma
- Radium-223 and Pain
- New Biomarker for Survival
- Quality of Life in Long-Term Survivors of Bladder Cancer
Approximately 3000 oncology experts gathered to hear about the latest advances in treating prostate, bladder, testicular, kidney, and penile cancers at the 2015 Genitourinary Cancers Symposium, held in Orlando, Florida. The symposium, cosponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology, explored the theme of “integrating biology into patient-centric care.” The following are news summaries of presentations of interest to oncology pharmacists.
Abiraterone and Metabolic Syndrome
Abiraterone is a highly effective and widely used drug in men with metastatic castration-resistant prostate cancer (CRPC). A preliminary study suggests that abiraterone may increase the risk of developing metabolic syndrome, and that the presence of metabolic syndrome is a significant risk factor for shorter progression-free survival in men with metastatic CRPC treated with abiraterone. No significant effect of metabolic syndrome was observed on overall survival in men with CRPC treated with abiraterone.
“These are preliminary results. Larger prospective trials are needed,” said Vincent Conteduca, MD, IRCCS, Istituto Scientifico Romagnola per lo Studio e la Cura del Tumori, Meldola, Italy. Although further study is needed, these findings may be important when selecting treatment, the authors said.
Androgen-deprivation therapy is known to increase the risk of metabolic syndrome and cardiovascular disease (CVD). The authors of this study wanted to look at metabolic alterations related to treatment with abiraterone, a novel hormonal therapy, and determine the impact of metabolic syndrome on progression-free survival and overall survival.
The retrospective study included 178 consecutive men with metastatic CRPC treated with abiraterone 100 mg and prednisone 5 mg twice a day in 28-day cycles after failing on previous treatment with docetaxel. Patients were evaluated at baseline and every 3 months for the presence of metabolic syndrome and cardiovascular events, and CT scans were obtained every 3 months.
At baseline, 67 of 178 patients (37.6%) met the definition of metabolic syndrome established by the modified Adult Treatment Panel III, or ATP III. Eleven additional patients developed metabolic syndrome on treatment with abiraterone.
Median progression-free survival was 4.7 months for those with metabolic syndrome versus 9 months for those without it (P = .003).
The presence of metabolic syndrome was associated with a 71% increased risk of disease progression or all-cause death compared with no metabolic syndrome, Conteduca noted.
Median overall survival was 14.7 months for those with metabolic syndrome and 22.3 months for those without it, but this difference was not statistically significant (P = .340).
CVD was reported in 26 patients (14.6%): 15 of 111 without metabolic syndrome (13.5%) and 11 of 68 with metabolic syndrome (16.4%).
The presence of preexisting CVD risk factors did not affect cardiovascular events during abiraterone treatment.
Conteduca V, Caffo O, Derosa L, et al. Metabolic syndrome in castration-resistent prostate cancer patients treated with abiraterone. J Clin Oncol. 2015;33(suppl 7):abstract 213. Poster presented at: 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL.
Obesity and Survival in Metastatic Renal-Cell Carcinoma
Obesity typically has negative health effects, including those related to cancer. Obesity and overweight are established risk factors for developing renal-cell carcinoma (RCC) and other types of solid cancers. But a new study suggests that obesity and overweight have a paradoxical effect by improving survival once patients develop metastatic RCC.
The study was based on more than 4000 patients with metastatic RCC who were enrolled in Pfizer-sponsored phase 2 and 3 clinical trials from 2003 to 2013. The impact of body mass index (BMI) was assessed on overall survival, progression-free survival, and overall response rate.
In 4657 patients included in the International mRCC Database Consortium (IMDC) biospecimen data set, a higher BMI was associated with improved likelihood of survival, longer time to treatment failure, and greater tumor shrinkage compared with normal or lower BMI. Among these patients, 2828 (61%) met criteria for being obese or overweight (ie, BMI ≥25 kg/m2), and 1829 (39%) were of normal weight or underweight (BMI <25 kg/m2).
A high BMI was associated with extended survival versus a lower BMI: 23.4 months versus 14.5 months, respectively (P = .0008). In an adjusted analysis, this difference translated to a 17% reduction in risk for mortality among patients with a high BMI.
Median progression-free survival was 8.2 months in those with high BMI versus 5.5 months in those with lower BMI, which translated to an 18% reduced risk of disease progression (P <.0001). Overall response rates to treatment were 25.3% versus 17.6%, respectively (P <.001).
Lead author Laurence Albiges, MD, PhD, a medical oncologist at the Institut Gustave Roussy, Paris, France, said that several lines of evidence suggest that higher BMI may be associated with more indolent RCC.
Data from The Cancer Genome Atlas suggest that fatty acid synthase (FASN) gene expression is associated with overall survival in RCC. In a multivariate analysis of the IMDC database (subjects in the current study), FASN staining was associated with prognosis but not overall survival.
Albiges noted that this finding was observed in clear cell RCC only. “We hypothesize that lipid metabolism may be modulated by the fat-laden tumor cells. FASN staining in the IMDC cohort is ongoing to better investigate the obesity paradox in metastatic RCC,” she said.
When stratified by line of therapy, the results remained unchanged, but when analyzed according to histological subtype, the favorable outcomes associated with higher BMI remained true only in clear cell RCC.
Albiges L, Hakimi AA, Lin X, et al. The impact of BMI on outcomes of patients with metastatic renal cell carcinoma treated with targeted therapy: an external validation data set and analysis of underlying biology from The Cancer Genome Atlas. J Clin Oncol. 2015;33(suppl 7):abstract 405. Poster presented at: 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL.
Radium-223 and Pain
Radium-223 is a novel alpha-emitting radiopharmaceutical that has been found to prolong lives of men with castration-resistant prostate cancer (CRPC) and bone metastasis. Results from the phase 3 ALSYMPCA trial showed that radium-223 prolonged overall survival by 2.8 months versus placebo (P <.001) and prolonged the time to first symptomatic skeletal event primarily associated with bone pain by 5.8 months compared with placebo (P <.001).
Radium-223 also has potential to reduce the severity of pain associated with bone metastases and to improve enjoyment of life, as shown in the safety results of a US Expanded Access Program (US EAP, a multicenter, prospective interventional, open-label phase 2 trial) that was initiated to provide radium-223 to patients with CRPC and symptomatic bone metastases.
In the US EAP, treatment with radium-223 achieved pain relief in 43% of patients, 19% had no change in pain, 28% had worsening pain, and 10% had a mix of worsening and improved pain. These findings were obtained in men not on opioids at baseline.
According to the authors, led by Michael Morris, MD, Memorial Sloan Kettering Cancer Center in New York City, the effect of radium-223 cannot be adequately interpreted in patients taking opioids at baseline due to the confounding effect of change in opioids after initiation of treatment.
Safety results were reported on 184 men with a median age of 70 years and median prostate-specific antigen (PSA) of 129 ng/mL; 59% received prior docetaxel, 10% were on current bisphosphonates, and 17% were on current denosumab. Of these men, 109 were not on opioids at baseline.
A significant improvement in pain severity (as assessed by mean pain score) was achieved by radium-223 treatment at all treatment visits (P < .05), which corresponded to a higher percentage of patients experiencing improvement versus worsening at each treatment visit. Among 97 patients with the potential for pain improvement at baseline (pain score ≥2), 57 (59%) experienced pain improvement during at least 1 on-treatment visit.
Radium-223 treatment was also associated with reduced pain interference in general activity, sleep, work, and walking, as well as with a higher percentage of patients who reported improved enjoyment of life.
Morris MJ, Sartor AO, Vogelzang NJ, et al. Effect of radium-223 dichloride (Ra-223) on pain from US EAP. J Clin Oncol. 2015;33(suppl 7):abstract 160. Poster presented at: 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL.
New Biomarker for Survival
Cumulative bone scan lesion area (BSLA) appears to be able to predict response to treatment and overall survival in patients with metastatic castration-resistant prostate cancer (CRPC). These findings have been replicated with different drug treatments.
BSLA is an imaging biomarker that is computed semiautomatically from whole-body scintigraphic imaging as a measure of overall bone tumor burden in CRPC.
The present study sought to test BSLA in 198 anonymous patients with CRPC enrolled in a treatment trial (127 on treatment and 71 on placebo). This cohort of men was independent from other cohorts used to develop the biomarker and initial validation studies, and the current study used a drug with a different mechanism of action from previous trials, reported Matthew Brown, PhD, Professor of Radiology at the University of California Los Angeles.
Standard of care whole-body scintigraphy was performed at baseline and week 12. BSLA was calculated at both time points. A 30% increase in BSLA was defined as disease progression, and a 30% decrease in BSLA was defined as response.
In a multivariate Cox regression analysis, low baseline BSLA <2000 mm2 was a significant prognostic factor (P = .003) and predicted longer survival (P <.001) compared with high BSLA ≥2000 mm2.
Looking at BSLA as a surrogate marker of outcome, patients without progressive disease according to BSLA at week 12 had significantly longer overall survival compared with patients who had progressive disease at that time point (P = .007).
Brown MS, Kim HJ, Chu GH, et al. Quantitative bone scan lesion area as an early surrogate outcome measure indicative of overall survival in metastatic castration-resistant prostate cancer. J Clin Oncol. 2015; 33(suppl 7):abstract 179. Poster presented at: 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL.
Quality of Life in Long-Term Survivors of Bladder Cancer
A survey of survivors of muscle invasive bladder cancer demonstrated that bladder-sparing trimodality therapy (TMT) was associated with improved quality of life (QOL) and bowel function compared with radical cystectomy (RC).
“Muscle-invasive bladder cancer can be treated with either muscle-sparing trimodality therapy or radical cystectomy. Both modalities are associated with 50% to 60% overall survival at 5 years. Both TMT and RC provide good long-term outcomes in these patients, but our study suggests that TMT has some significant advantages,” said presenting author Kimberly S. Mak, MD, Harvard Radiation Oncology Program, Boston, MA. “Whether these significant findings translate into clinically meaningful differences requires further study.”
The cross-sectional, multi-institutional study compared long-term QOL in patients aged 18 years or older with nonmetastatic muscle invasive bladder cancer diagnosed between 1990 and 2011 who had been disease free for at least 2 years. A questionnaire was sent to 226 eligible patients and was returned by 173 patients, for a response rate of 77%. Instruments used to assess QOL included EuroQOL (EQ)-5D 3L and EQ VAS, EORTC QLQ-C30, and Expanded Prostate Cancer Index Composite (EPIC) – Bowel Domain.
Sixty-four patients were treated with TMT and 109 with RC. Of those treated with RC, 89 had an ileal conduit and 18 had neobladder diversions. Median time from diagnosis to questionnaire was 9 years for the TMT group and 6 years for the RC group.
When baseline characteristics were compared between the 2 treatment groups, no significant difference was observed for age at diagnosis, age at the time of responding to the questionnaire, sex, smoking status, clinical stage, or comorbidities.
In a univariate analysis, TMT was associated with better general QOL compared with RC, with a significant 4.8-point difference on the EQ-5D 3L Visual Analog Scale (P = .07) and a 7.4-point difference on the EORTC QLQ-C30 (P = .02).
In a multivariate analysis, adjusted for age, time from diagnosis, year of treatment, sex, and comorbidity status, TMT achieved significantly better general QOL by an average of 6 or 7 points (P = .005). Looking at bowel function on multivariate analysis, TMT achieved an average increment of 4.5 points compared with RC on the EPIC bowel function subscale. However, there was no difference between treatments on the EPIC bowel bother subscale. Both groups had similar urinary QOL, as assessed by the EORTC-QLQ-BLM30 instrument.
Mak KS, Smith A, Eidelman A, et al. Quality of life in long-term survivors of muscle-invasive bladder cancer. J Clin Oncol. 2015;33(suppl 7):abstract 319. Poster presented at: 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL.