Publications by authors named "Daniel Heng"
Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF).
View Article and Find Full Text PDFBackground And Objective: Patients receiving immune checkpoint blockade (ICB) therapy may experience periods of prolonged disease control without a need for systemic therapy. Treatment-free survival (TFS) is an important measure for this period, but no data are available for patients with metastatic renal cell carcinoma (mRCC) starting first-line agents. Our aim was to analyze TFS outcomes for patients with mRCC starting first-line therapy.
View Article and Find Full Text PDFBackground: Neuroendocrine prostate cancer (NEPC) encompasses pure NEPC and tumors with mixed adenocarcinoma and neuroendocrine histology. While NEPC is thought to confer a poor prognosis, outcome data are sparse, making risk stratification and treatment decisions difficult for clinicians.
Methods: This retrospective study identified patients with morphological and/or immunohistochemical NEPC features on pathological review of high-grade prostate cancer cases.
Background And Objective: Lenvatinib is a multitargeted tyrosine kinase inhibitor (TKI) used in the upfront and refractory settings for metastatic renal cell carcinoma (mRCC). However, there are limited data on the efficacy of subsequent TKI therapies after lenvatinib. We investigated the activity of TKI therapies after lenvatinib in patients with mRCC.
View Article and Find Full Text PDFObjective: To evaluate and compare the outcomes of patients with localised renal cell carcinoma (RCC) with and without sarcomatoid features and the impact of this on cancer recurrence and survival.
Material And Methods: The Canadian Kidney Cancer information system database was used to identify patients diagnosed with localised RCC between January 2011 and December 2022. Patients with pT1-T3, n Nx-N0N1, M0 stage and documented sarcomatoid status were included.
Purpose: Postoperative prognostic tools allow for improved prediction of future recurrence risk, patient counseling, and assessment of eligibility for adjuvant treatments and ensure appropriate follow-up surveillance. The purpose of this analysis was to validate existing prognostic models for patients with kidney cancer.
Materials And Methods: The Canadian Kidney Cancer information system is a prospective cohort of patients managed at 14 institutions since January 1, 2011, to present.
Article Synopsis
- The review focuses on the recent advancements in treatment options for metastatic renal cell carcinoma (mRCC), highlighting the importance of selecting appropriate first- and second-line therapies based on the latest evidence.
- First-line treatments include immune checkpoint inhibitor combinations and tyrosine kinase inhibitors, with four regimens approved internationally; however, treatment decisions are complicated by the absence of head-to-head trials and standardized biomarkers.
- Clinicians must consider various factors, such as the IMDC risk score and patient preferences, when transitioning between treatment lines to ensure personalized and effective care for mRCC patients.
Docetaxel Versus Androgen-Receptor Signaling Inhibitors (ARSI) as Second-Line Therapy After Failure of First-Line Alternative ARSI for the Elderly ≥ 75 Years Old With Metastatic Castration-Resistant Prostate Cancer (mCRPC): A SPARTACUSS-Meet-URO 26 Real-World Study.
Clin Genitourin Cancer
December 2024
Article Synopsis
- The study focuses on the effectiveness and safety of second-line treatment options (docetaxel vs. alternative ARSI) for patients aged 75 and older who have metastatic castration-resistant prostate cancer (mCRPC) after failing first-line androgen receptor signaling inhibitors (ARSIs).
- Researchers analyzed a group of 122 elderly patients, finding no significant differences in overall survival or progression-free survival when comparing those who received docetaxel to those who received an alternative ARSI.
- The results suggest that both treatment options are similar for elderly patients, providing useful insights despite the limitations of a small and retrospective study design.
Article Synopsis
- A study compared the combination treatment of tivozanib and nivolumab against tivozanib alone for patients with advanced renal cell carcinoma who progressed after one or two prior therapies, focusing on the post-immune checkpoint inhibitor (ICI) setting.
- The TiNivo-2 trial included 343 patients from 190 sites across multiple continents, with the primary goal of evaluating progression-free survival (PFS) as the main outcome.
- Results showed that the median PFS was 5.7 months for the combination therapy and 7.4 months for tivozanib monotherapy, indicating no significant advantage for the combination treatment based on the hazard ratio.
JCO Mesenchymal-epithelial transition (MET) signaling pathway plays a role in the pathogenesis of selected patients with papillary renal cell carcinoma (PRCC). In the phase II PAPMET trial (ClinicalTrials.gov identifier: NCT02761057), cabozantinib significantly prolonged progression-free survival and improved objective response rate compared with sunitinib in patients with advanced PRCC.
View Article and Find Full Text PDFOutcomes of First-Line Abiraterone Acetate or Enzalutamide for Older Adults With Metastatic Castration-Resistant Prostate Cancer According to Use of Upfront Docetaxel for Metastatic Castration-Sensitive Prostate Cancer in an International Multicenter Registry: A SPARTACUSS-Meet-URO 26 Study.
Clin Genitourin Cancer
October 2024
Article Synopsis
- Managing metastatic castration-resistant prostate cancer (mCRPC) in men aged 75 and older is difficult due to limited research, but common first-line treatments include abiraterone acetate plus prednisone (AA) and enzalutamide (Enza).
- A study analyzed 337 patients aged 75+ who started AA or Enza and found no significant differences in survival rates or adverse effects between those who previously used docetaxel (D) and those who only received androgen deprivation therapy (ADT).
- The results imply that elderly men with mCRPC can expect similar outcomes and side effect profiles from AA or Enza, irrespective of prior D treatment, though the study's retrospective nature
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).
View Article and Find Full Text PDFArticle Synopsis
- * Methods: Researchers analyzed data from 94 patients treated at 29 institutions, assessing various factors like type of therapy, timing of recurrence, and patient risk categories, while also monitoring treatment-related side effects.
- * Key Findings: The study revealed an 18-month PFS rate of 45% and overall survival (OS) rate of 85%, with common treatment-related side effects including skin toxicity and fatigue; it did have limitations due to patient selection.
Article Synopsis
- The study investigated the effectiveness of nivolumab, an immunotherapy drug, used before and after surgery in patients with high-risk renal cell carcinoma compared to traditional surgery alone.
- It was a randomized phase 3 trial involving 819 patients across multiple sites in the US and Canada, who were assigned to either the nivolumab plus surgery group or surgery only group.
- The primary outcome measured was recurrence-free survival, with safety being assessed for all patients who started treatment, and the trial has been officially closed to new participants.
Background: The association between objective imaging response and first line immune checkpoint inhibitor (ICI) therapy regimes in advanced melanoma remains uncharacterized in routine practice.
Methods: We conducted a multi-center retrospective cohort analysis of advanced melanoma patients receiving first line ICI therapy from August 2013-May 2020 in Alberta, Canada. The primary outcome was likelihood of RECIST v1.
Multidisciplinary systemic and local therapies for metastatic renal cell carcinoma: a narrative review.
Expert Rev Anticancer Ther
August 2024
Introduction: Systemic and local therapies for patients with metastatic renal cell carcinoma (mRCC) are often challenging despite the evolution of multimodal cancer therapies in the last decade. In this review, we will focus on recent multidisciplinary approaches for patients with mRCC.
Areas Covered: Systemic therapies for patients with mRCC have been garnering attention particularly after the approval of immuno-oncology (IO) agents, including anti-programmed death 1/programmed death-ligand 1.
Background: Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens.
Materials And Methods: Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively.
Aims: To resolve the ongoing controversy surrounding the impact of teratoma (TER) in the primary among patients with metastatic testicular non-seminomatous germ-cell tumours (NSGCT).
Patients And Methods: Using the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium database, we compared the survival probabilities of patients with metastatic testicular GCT with TER (TER) or without TER (NTER) in their primaries corrected for known prognostic factors. Progression-free survival (5y-PFS) and overall survival at 5 years (5y-OS) were estimated by the Kaplan-Meier method.
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.
View Article and Find Full Text PDFPatients with brain metastases (BrM) from renal cell carcinoma and their outcomes are not well characterized owing to frequent exclusion of this population from clinical trials. We analyzed data for patients with or without BrM using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). A total of 389/4799 patients (8.
View Article and Find Full Text PDFArticle Synopsis
- Immune-related adverse events (irAEs) linked to immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC) patients may enhance overall survival, though the relationship between irAE severity and survival is not well understood.
- This study analyzed data from 803 NSCLC patients treated with ICIs between March 2014 and November 2021 in Alberta, Canada, focusing on those who experienced clinically meaningful irAEs that affected their treatment regimen.
- The findings suggest a connection between the occurrence of irAEs and improved overall survival, with extensive data analysis conducted to determine factors influencing this outcome while avoiding biases in the evaluation.
Real-world Assessment of Clinical Outcomes in Patients with Metastatic Renal Cell Carcinoma with or Without Sarcomatoid Features Treated with First-line Systemic Therapies.
Eur Urol Oncol
June 2024
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.
Article Synopsis
- High-dose chemotherapy with autologous stem-cell transplantation (HDC-ASCT) is a standard treatment for patients with metastatic germ cell tumors (mGCTs) who relapse after conventional chemo, and this study reviews its effectiveness in Alberta, Canada, over 20 years.
- A review of 43 patients treated with HDC-ASCT revealed a median age of 28, with most having non-seminoma tumors; survival rates showed 42% were disease-free at last follow-up.
- The findings suggest that HDC-ASCT is an effective second-line therapy for mGCT, with indications that tandem transplants may yield better outcomes, though the results are limited by a small sample size.