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PurposeThe TAXYNERGY trial (ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and MethodsPatients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve $ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed $ 50% PSA decline versus historical control (TAX327). The primary biomarker endpoint was analysis of post-treatment CTCs to confirm the hypothesis that clinical response was associated with taxane drug-target engagement, evidenced by decreased percent androgen receptor nuclear localization (%ARNL) and increased microtubule bundling. ResultsSixty-three patients were randomly assigned to docetaxel (n = 41) or cabazitaxel (n = 22); 44.4% received prior potent androgen receptor-targeted therapy. Overall, 35 patients (55.6%) had confirmed $ 50% PSA responses, exceeding the historical control rate of 45.4% (TAX327). Of 61 treated patients, 33 (54.1%) had $ 30% PSA declines by C4 and did not switch taxane, 15 patients (24.6%) who did not achieve $ 30% PSA declines by C4 switched taxane, and 13 patients (21.3%) discontinued therapy before or at C4. Of patients switching taxane, 46.7% subsequently achieved $ 50% PSA decrease. In 26 CTC-evaluable patients, taxane-induced decrease in %ARNL (cycle 1 day 1 v cycle 1 day 8) was associated with a higher rate of $ 50% PSA decrease at C4 (P = .009).Median composite progression-free survival was 9.1 months (95% CI, 4.9 to 11.7 months); median overall survival was not reached at 14 months. Common grade 3 or 4 adverse events included fatigue (13.1%) and febrile neutropenia (11.5%). ConclusionThe early taxane switch strategy was associated with improved PSA response rates versus TAX327. Taxane-induced shifts in %ARNL may serve as an early biomarker of clinical benefit in patients treated with taxanes.

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BackgroundFor Canadian men, prostate cancer (PCa) is the most common cancer and the 3rd leading cause of cancer mortality. Men dying of PCa do so after failing castration. The management of metastatic castration-resistant prostate cancer (mCRPC) is complex and the associated drug treatments are increasingly costly. The objective of this study was to estimate the cost of drug treatments over the mCRPC period, in the context of the latest evidence-based approaches.MethodsTwo Markov models with Monte-Carlo microsimulations were developed in order to simulate the management of the disease and to estimate the cost of drug treatments in mCRPC, as per Quebec’s public healthcare system. The models include recently approved additional lines of treatment after or before docetaxel (i.e. abiraterone and cabazitaxel). Drug exposure and survival were based on clinical trial results and clinical practice guidelines found in a literature review. All costs were assigned in 2013 Canadian dollars ($). Only direct drug costs were estimated.ResultsThe mean cost of mCRPC drug treatments over an average period of 28.1 months was estimated at $48,428 per patient (95% Confidence Interval: $47,624 to $49,232). The mean cost increased to $104,071 (95% CI: $102,373 - $105,770) per patient when one includes abiraterone initiation prior to docetaxel therapy. Over the mCRPC period, luteinizing hormone-releasing hormone agonists (LHRHa) prescribed to maintain castrate testosterone levels accounted for 20.4% of the total medication cost, whereas denosumab prescribed to decrease bone-related events accounted for 30.5% of costs. When patients received cabazitaxel in sequence after abiraterone and docetaxel, the mCRPC medications cost per patient per month increased by 60.2%. The total cost of medications for the treatment of each annual Canadian cohort of 4,000 mCRPC patients was estimated at $ 193.6 million to $416.3 million.ConclusionsOur study estimates the direct drug costs associated with mCRPC treatments in the Canadian healthcare system. Recently identified effective yet not approved therapies will become part of the spectrum of mCRPC treatments, and may potentially increase the cost.

Introduction: Clinical trial data has shown pazopanib to be noninferior in overall survival (OS) compared to sunitinib as first-line treatment for metastatic renal cell carcinoma (mRCC). The purpose of this study was to evaluate outcomes and compare dose-modifying toxicities of mRCC patients treated with suntinib or pazopanib in the real-world setting. Methods: Data were collected on mRCC patients using the prospective Canadian Kidney Cancer Information System (CKCis) database from January 2011 to November 2015. Statistical analyses were performed using Cox regression adjusted for several risk factors and the Kaplan-Meier method. Results: We identified 670 patients treated with sunitinib (n=577) and pazopanib (n=93). There were no significant differences in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups (p=0.807). Patients treated with sunitinib had improved OS compared with pazopanib (median 31.7 vs. 20.6 months, p=0.028; adjusted hazard ratio [aHR] 0.60; 95% confidence interval [CI] 0.38-0.94). Time to treatment failure (TTF) was numerically, but not statistically, improved with sunitinib (medians 11.0 vs. 8.4 months, p=0.130; aHR 0.87; 95% CI 0.59-1.28). Outcomes with individualized dosing on sunitinib were unavailable for this analysis. Patients treated with sunitinib had a higher incidence of mucositis, hand-foot syndrome, and gastroesophageal reflux disease; patients treated with pazopanib had a higher incidence of hepatotoxicity. Conclusions: In Canadian patients with mRCC, treatment with sunitinib appears to be associated with an improved OS compared to pazopanib in the first-line setting. Patient selection factors and the contemporary practice of individualized dosing with sunitinib may contribute to these real-world outcomes and warrant further investigation.

Appropriately timed neoadjuvant chemotherapy with a highly effective regimen rapidly restores normal swallowing, maintains nutritional status, and obviates the need for invasive tube feeding in patients with significant dysphagia from esophageal adenocarcinoma.

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Background: Inaccurate risk classification and the burden of unnecessary biopsies are a challenge due to the limited ability of current risk assessment tools and modalities to diagnose prostate cancer (PCa) and distinguish indolent from aggressive disease. This systematic review assesses newly developed tests and interventions with high evidence of clinical utility that might be adopted in clinical practice during PCa management before initial and repeat biopsy, after positive biopsy, and after radical treatment. Methods: The Cochrane, Embase, MED-LINE, and Web of Science databases were searched for studies pertaining to the clinical utility of PCa diagnostic tests. Outcomes of interest were (1) a measure of the percentage of altered decision-making, (2) decrease in number of unnecessary biopsies, (3) decrease or increase in treatment intensity, and (4) risk reclassification after test results. Results: The search yielded 2,940 articles, of which 46 met the inclusion criteria. We found clinical utility evidence on the Prostate Health Index (PHI), 4Kscore test, MRI, OncotypeDX, Decipher test, Prolaris, ConfirmMDx, Progensa PCA3, NADiA ProsVue, and ProMark. No evidence was identified for Prostarix, ProstaVysion, Prostate Core Mitomic Test, and Mi-Prostate Score. The interventions demonstrated their clinical utility in terms of change in treatment recommendations, decrease/increase in interventional treatment, decrease in biopsy, and risk reclassification. At diagnosis after a positive biopsy, ProMark, OncotypeDX, Prolaris, and MRI guided the use of active surveillance. Use of NADiA ProsVue, Decipher, and Prolaris aided in the decision to add adjuvant therapy post-prostatectomy. PHI, 4Kscore, and MRI used prior initial and repeat biopsies, and ConfirmMDx and Progensa PCA3 used prior repeat biopsies to improve prediction of biopsy outcome, allowing a decrease in unnecessary biopsies. Conclusions: This systematic review suggests that implementation of these tests in clinical practice could effectuate personalized treatment of PCa. Further clinical and economic evaluation studies of long-term PCa outcomes are warranted to provide further guidance.