Publications by authors named "Vincent Castonguay"

Intrapatient intermetastatic heterogeneity (IIH) has been demonstrated in metastatic castration-resistant prostate cancer (mCRPC) patients and is of the utmost importance for radiopharmaceutical therapy (RPT) eligibility. This study was designed to determine the prevalence of IIH and RPT eligibility in mCRPC patients through a triple-tracer PET imaging strategy. This was a multisite prospective observational study in which mCRPC patients underwent both F-FDG and Ga-prostate-specific membrane antigen (PSMA)-617 PET/CT scans.

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Immunotherapy-based systemic treatment (ST) is the standard of care for most patients diagnosed with metastatic renal cell carcinoma (mRCC). Cytoreductive nephrectomy (CN) has historically shown benefit for select patients with mRCC, but its role and timing are not well understood in the era of immunotherapy. The primary objective of this study is to assess outcomes in patients who received ST only, CN followed by ST (CN-ST), and ST followed by CN (ST-CN).

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Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making.

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Background: Cabozantinib, an oral multi-targeted tyrosine kinase inhibitor (TKI), has demonstrated efficacy in metastatic renal cell carcinoma (mRCC). The association between toxicity and therapeutic effectiveness has been established with other TKIs. We investigated whether cabozantinib dose reductions, a surrogate for toxicity and adequate drug exposure, were associated with improved clinical outcomes in mRCC.

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Article Synopsis
  • Metastatic renal cell carcinoma (mRCC) patients treated with immunotherapies (IO) show better overall survival outcomes compared to those treated with targeted therapies (TT), particularly in those with or without sarcomatoid features.
  • A study involving 1,202 patients assessed the impact of different first-line systemic therapies, revealing that IO treatment led to a significantly longer median survival than TT for both nonsarcomatoid (72 vs. 48 months) and sarcomatoid (48 vs. 18 months) patients.
  • The study utilized real-world data from the IMDC database and applied statistical models to ensure balanced comparisons, ultimately highlighting the effectiveness of IO in metastatic RCC treatment.
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Importance: The KEYNOTE-826 randomized clinical trial showed statistically significant and clinically meaningful survival benefits with the addition of pembrolizumab to chemotherapy with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer. Treatment effects in patient subgroups of the study population are unknown.

Objective: To assess efficacy outcomes in patient subgroups of KEYNOTE-826.

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Article Synopsis
  • The study examines the integration and use of systemic therapies for metastatic renal cell carcinoma (mRCC) in Canada between 2011 and 2021, highlighting significant advancements in treatment options over the years.
  • Data was collected from the Canadian Kidney Cancer Information System, involving 4,107 patients, with a focus on treatment trends and patient demographics across two separate time cohorts.
  • The findings indicate a rise in the use of immune checkpoint inhibitors and a shift towards vascular endothelial growth factor-tyrosine kinase inhibitors as subsequent treatments, with about 18-24% of patients participating in clinical trials based on their treatment line.
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Article Synopsis
  • The KEYNOTE-826 trial tested the effectiveness of pembrolizumab combined with chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer, showing significant improvements in survival rates compared to placebo plus chemotherapy.
  • At the final data analysis, median overall survival (OS) for those receiving pembrolizumab was significantly higher than for those on placebo, with results of 28.6 months vs. 16.5 months in one group and similar patterns in others, indicating strong benefits across various patient populations.
  • However, there were more grade ≥3 adverse events reported in the pembrolizumab group (82.4%) compared to the placebo group (75.4%), highlighting the need to consider potential side effects alongside treatment
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Introduction: Several recent randomized trials evaluated the impact of adjuvant immune checkpoint inhibitor (ICI)-based therapy on post-surgical outcomes in renal cell carcinoma (RCC), with disparate results. The objective of this consensus statement is to provide data-driven guidance regarding the use of ICIs after complete resection of clear-cell RCC in a Canadian context.

Methods: An expert panel of genitourinary medical oncologists, urologic oncologists, and radiation oncologists with expertise in RCC management was convened in a dedicated session during the 2022 Canadian Kidney Cancer Forum in Toronto, Canada.

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Background: In the KEYNOTE-826 study, the addition of the anti-PD-1 monoclonal antibody pembrolizumab to chemotherapy with or without bevacizumab improved overall survival and progression-free survival (primary endpoints) versus placebo plus chemotherapy with or without bevacizumab, with manageable toxicity, in patients with persistent, recurrent, or metastatic cervical cancer. In this Article, we report patient-reported outcomes (PROs) from KEYNOTE-826.

Methods: KEYNOTE-826 is a multicentre, randomised, phase 3 trial in 151 cancer treatment centres in 19 countries.

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The androgen inactivating UGT2B28 pathway emerges as a predictor of progression in prostate cancer (PCa). However, the clinical significance of UGT2B28 tumoral expression and its contribution to PCa progression remain unclear. Using the Canadian Prostate Cancer Biomarker Network biobank (CPCBN; n = 1512), we analyzed UGT2B28 tumor expression in relation to clinical outcomes in men with localized PCa.

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Background: The role and sequencing of combination immuno-oncology (IO) therapy following progression on or after first-line IO therapy has not been well-established. The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology (FRACTION) program is an open-label, phase 2 platform trial designed to evaluate multiple IO combinations in patients with advanced renal cell carcinoma (aRCC) who progressed during or after prior IO therapy. Here, we describe the results for patients treated with nivolumab plus ipilimumab.

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Purpose: With the integration of immunotherapy (IO) agents in the management of metastatic renal cell carcinoma (mRCC), there has been interest in the combined use with radiation therapy (RT). However, real world data are limited. The purpose of this study was to evaluate outcomes in patients with mRCC receiving both RT and IO compared with IO alone.

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Introduction: Ipilimumab plus nivolumab was associated with a survival benefit in a phase III clinical trial of first-line treatment for metastatic renal cell carcinoma (mRCC). In this study, mRCC patients from the Canadian Kidney Cancer Information System (CKCis) database who received first-line ipilimumab plus nivolumab were analyzed to determine the safety and outcomes in a real-world setting.

Patients And Methods: Patients who received ipilimumab plus nivolumab as first-line therapy for mRCC in CKCis, were identified, and the amount of treatment received, discontinuation rates, and reasons for discontinuing treatment were determined.

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Background: Pembrolizumab has efficacy in programmed death ligand 1 (PD-L1)-positive metastatic or unresectable cervical cancer that has progressed during chemotherapy. We assessed the relative benefit of adding pembrolizumab to chemotherapy with or without bevacizumab.

Methods: In a double-blind, phase 3 trial, we randomly assigned patients with persistent, recurrent, or metastatic cervical cancer in a 1:1 ratio to receive pembrolizumab (200 mg) or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy and, per investigator discretion, bevacizumab.

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Background: The prevalence of multiple myeloma is increasing and there is a need to evaluate escalating therapy costs (Canadian Cancer Statistics A, 2020). The MYX.1 phase II trial showed that high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone (wKCD) is efficacious in relapsed and refractory disease.

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Article Synopsis
  • A multidisciplinary continuing medical education (CME) program was created to improve knowledge gaps related to quality indicators in kidney cancer care, delivered by experts in four Canadian cities.
  • Fifty-two participants completed tests before and after the CME, showing a significant improvement from an average pre-CME score of 61% to 70% post-CME.
  • The program showed beneficial outcomes, particularly for urologists, and suggests the need for implementation across more locations to enhance kidney cancer care knowledge.
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Background: The anticipated clinical outcome of the standard/control arm is an important parameter in the design of randomized phase 3 (RP3) trials to properly calculate sample size, power, and study duration. Changing patterns of care or variation in the study population enrolled may lead to a deviation from the initially anticipated outcome. The authors hypothesized that recent changes in patterns of care in epithelial ovarian cancer (EOC) have led to challenges in correctly estimating the outcome of control groups.

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Objective: Treatment options remain limited for women with relapsed/metastatic endometrial cancer (EC). Angiogenesis is one of the major components of tumor progression and thus an attractive target. The aim of this phase II trial was to assess the efficacy and tolerability of sunitinib, an oral multitargeted receptor tyrosine-kinase inhibitor with antiangiogenic and antitumor activity in the treatment of recurrent EC.

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Purpose: Preclinical data suggest that exposure to PARP inhibitors (PARPi) may compromise benefit to subsequent chemotherapy, particularly platinum-based regimens, in patients with BRCA1/2 mutation carrier ovarian cancer (PBMCOC), possibly through the acquisition of secondary BRCA1/2 mutations. The efficacy of chemotherapy in the PARPi-resistant setting was therefore investigated.

Experimental Design: We conducted a retrospective review of PBMCOC who received chemotherapy following disease progression on olaparib, administered at ≥200 mg twice daily for one month or more.

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Purpose: The purpose was to assess the activity and side effect profile of ENMD-2076, an oral anti-angiogenic and anti-proliferative kinase inhibitor, in platinum-resistant recurrent epithelial ovarian cancer (EOC), fallopian tube or peritoneal cancer. Archival tumour tissue was obtained for correlative analyses.

Experimental Design: This was an open-label single-arm Phase II study of single agent ENMD-2076 taken daily orally (PO).

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In response to high levels of DNA damage, catalytic activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) triggers necrotic death because of rapid consumption of its substrate beta-nicotinamide adenine dinucleotide and consequent depletion of ATP. We examined whether there are other consequences of PARP activation that could contribute to cell death. Here, we show that PARP activation reaction in vitro becomes acidic with release of protons during hydrolysis of beta-nicotinamide adenine dinucleotide.

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