Publications by authors named "Srikala S Sridhar"
Background: In PIVOT-02, bempegaldesleukin (BEMPEG), a pegylated interleukin-2 cytokine prodrug, in combination with nivolumab (NIVO), a Programmed cell death protein 1 inhibitor, demonstrated the potential to provide additional benefits over immune checkpoint inhibitor monotherapy in patients with urothelial carcinoma, warranting further investigation. We evaluated BEMPEG plus NIVO in cisplatin-ineligible patients with previously untreated locally advanced or metastatic urothelial carcinoma.
Methods: This open-label, multicenter, single-arm, phase II study enrolled patients with locally advanced/surgically unresectable or metastatic urothelial carcinoma and who were ineligible for cisplatin-based treatment.
Introduction: Bone metastases (BM) in metastatic urothelial carcinoma (mUC) may impact patient outcomes, but their independent effect with immune checkpoint inhibitors (ICIs) is uncertain. We aimed to assess the impact of BM and PD-L1 status on outcomes in mUC patients treated with ICIs.
Patients And Methods: This post hoc analysis of the DANUBE study included 1032 mUC patients treated with durvalumab (D), D + tremelimumab (T), or standard chemotherapy (SoC).
Article Synopsis
- Clinical trials in genitourinary oncology are primarily classified as industry-sponsored trials (ISTs) led by pharmaceutical companies, or investigator-initiated trials (IITs) spearheaded by academic researchers, with both playing critical roles in advancing cancer treatment.
- A study analyzing data from the US, Canada, France, and the UK found a total of 5,834 GU trials from 2007 to 2021, with a near-equal distribution of ISTs and IITs, though post-2017 saw a notable increase in ISTs, particularly in Canada and the UK.
- The widening gap between ISTs and IITs is likely due to funding and resource constraints for researchers
Background: Gemcitabine plus cisplatin (GC) is a highly active and commonly used regimen in locally advanced/metastatic urothelial carcinoma (la/mUC). With GC, cisplatin is dosed at 70 mg/m on day 1 of a 3-week cycle; however, for many patients, impaired renal or cardiac function, neuropathy, or poor performance status (PS) can preclude the use of cisplatin. A promising alternative is split-dose GC, in which the cisplatin dose is divided over 2 days.
View Article and Find Full Text PDFPlatinum-based chemotherapy has been the standard first-line (1L) treatment for advanced urothelial carcinoma (UC) for decades, based on the proven efficacy and established safety profiles of cisplatin- and carboplatin-based regimens. With the emergence of novel regimens, it is important to reevaluate and contextualize the role of 1L platinum-based chemotherapy. Platinum-based chemotherapy followed by avelumab 1L maintenance in patients without disease progression following platinum-based chemotherapy was established as a standard 1L regimen based on the JAVELIN Bladder 100 phase III trial.
View Article and Find Full Text PDFThe treatment landscape for patients with advanced urothelial carcinoma continues to evolve. Enfortumab vedotin plus pembrolizumab has received Food and Drug Administration approval based on recent phase 3 trial data showing superior efficacy compared with first-line platinum-based chemotherapy; however, its distinct toxicity profile may make it less suitable for some patients, and availability in some countries may be limited by cost considerations. Consequently, platinum-based chemotherapy is expected to remain an important first-line treatment option.
View Article and Find Full Text PDFDespite recent advances in the management of urothelial cancer (UC), cisplatin-based combination chemotherapy regimens remain critical. However, their use can be complicated in patients with chronic kidney disease (CKD), which is not uncommon in UC patients. Based on the Galsky criteria for cisplatin ineligibility, most patients with CKD will be excluded from receiving cisplatin-based chemotherapy altogether.
View Article and Find Full Text PDFObjectives: Immune checkpoint inhibitors (ICIs) are indicated for metastatic urothelial cancer (mUC), but predictive and prognostic factors are lacking. We investigated clinical variables associated with ICI outcomes.
Methods: We performed a multicentre retrospective cohort study of 135 patients who received ICI for mUC, 2016-2021, at three Canadian centres.
Article Synopsis
- The study investigates the effectiveness of geriatric assessment and management (GA + M) and remote symptom monitoring (RSM) on improving treatment tolerability and quality of life in older adults with metastatic prostate cancer receiving androgen receptor axis-targeted therapy (ARATs).
- TOPCOP3 is a pilot clinical trial designed with four treatment approaches, including combinations of GA + M and RSM, and will track 168 patients over six months at cancer centers in Toronto.
- The main outcomes measured will be severe toxicity and quality of life, along with secondary outcomes like fatigue and depression, while also evaluating the feasibility and acceptability of these interventions.
Immunotherapy (IO) with or without targeted therapy (TT) is the standard treatment for patients with metastatic clear cell renal cell carcinoma (RCC). The evidence supporting their use in metastatic nonclear cell renal cell carcinoma (nccRCC) subtypes is based on small prospective trials and retrospective analyses. Here, we report survival outcomes for patients with metastatic nccRCC treated with IO and/or TT at the Princess Margaret Cancer Centre, Toronto, ON, Canada.
View Article and Find Full Text PDFBackground And Objective: In comparison to chemotherapy, enfortumab vedotin (EV) prolonged overall survival in patients with previously treated advanced urothelial carcinoma in EV-301. The objective of the present study was to assess patient experiences of EV versus chemotherapy using patient-reported outcome (PRO) analysis of health-related quality of life (HRQoL).
Methods: For patients in the phase 3 EV-301 trial randomized to EV or chemotherapy we assessed responses to the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, weekly for the first 12 wk, and then every 12 wk until discontinuation.
Article Synopsis
- Cisplatin-based neoadjuvant chemotherapy (NAC) is commonly used in muscle-invasive bladder cancer patients but can lead to renal toxicity, and radical cystectomy (RC) itself is a risk factor for renal injury.
- An analysis of 234 patients showed a significant decrease in estimated glomerular filtration rate (eGFR) after receiving NAC, with a 17% decline and an increase in chronic kidney disease stage ≥3 from 27% to 50% one year after surgery.
- In comparison, a control group that underwent RC without NAC had a smaller eGFR decline of 6% and a baseline higher incidence of stage ≥3 CKD, highlighting the renal risks associated with NAC prior to surgery
Article Synopsis
- - This study analyzed data from clinical trials to identify patient characteristics linked to long-term survival in those with metastatic urothelial carcinoma treated with immune checkpoint inhibitors.
- - Out of 360 patients, 24.4% survived over 2 years following treatment, with factors such as ECOG performance status, PD-L1 expression, and specific laboratory results significantly influencing their long-term survival outcomes.
- - The findings suggest that understanding these baseline characteristics can help predict which patients are more likely to benefit from treatments like durvalumab or durvalumab plus tremelimumab.
Background: In the JAVELIN Bladder 100 phase 3 trial, avelumab first-line maintenance + best supportive care (BSC) prolonged overall survival (OS) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (advanced UC) without progression after first-line platinum-based chemotherapy.
Objective: To report post hoc analyses of subgroups defined by the duration of first-line chemotherapy and interval before maintenance.
Design, Setting, And Participants: Patients with advanced UC without progression after four to six cycles of platinum-based chemotherapy and a 4-10-wk interval after chemotherapy (n = 700) were randomized to receive avelumab + BSC or BSC alone.
Key Points: Many patients with metastatic urothelial carcinoma are deemed cisplatin-ineligible because of reduced kidney function. Options include split-dose cisplatin or carboplatin. There was no significant association between regimen type and AKI.
View Article and Find Full Text PDFThe COVID-19 pandemic precipitated the acute and efficient rollout of telehealth and virtual health care around the world. This review article focuses on the adoption of virtual care in the management of oncology patients, and discusses how virtual care offers the potential for large-scale, positive impacts on access to clinical trials. Virtual care during and following the peak of the pandemic has been found to be both safe and efficacious for oncology patients.
View Article and Find Full Text PDFContext: Bladder cancer (BC) is common worldwide and poses a significant public health challenge. External risk factors and the wider exposome (totality of exposure from external and internal factors) contribute significantly to the development of BC. Therefore, establishing a clear understanding of these risk factors is the key to prevention.
View Article and Find Full Text PDFArticle Synopsis
- Researchers wanted to compare two treatments for bladder cancer: one is surgery (radical cystectomy), and the other is a combination of surgery, chemotherapy, and radiation (trimodality therapy).
- They studied 722 patients with similar cancer stages from different hospitals in the USA and Canada to see which treatment worked better.
- The main goal was to see which treatment helped patients live longer without their cancer spreading, and they used complex methods (like matching patients) to ensure fair comparisons.
The treatment paradigm for metastatic castrate-sensitive prostate cancer (mCSPC) has evolved rapidly in the past decade with the approval of several life-prolonging therapies including docetaxel chemotherapy and multiple androgen receptor pathway inhibitors (ARPI) in combination with androgen deprivation therapy (ADT). Recently reported phase-three trials have demonstrated a survival benefit of upfront triplet therapy with ADT, docetaxel plus either abiraterone acetate or darolutamide when compared to ADT plus docetaxel alone. However, multiple questions including the incremental benefit of docetaxel to a combination of ADT and ARPI, the timing of ARPI, optimal patient selection for triplet therapy and clinical and genomic biomarkers still remain to be answered.
View Article and Find Full Text PDFBackground: In the phase 3 JAVELIN Bladder 100 trial, avelumab first-line (1L) maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (aUC) who were progression-free following 1L platinum-based chemotherapy, leading to regulatory approval in various countries.
Objective: To analyze clinically relevant subgroups from JAVELIN Bladder 100.
Design, Setting, And Participants: Patients with unresectable locally advanced or metastatic UC without progression on 1L gemcitabine + cisplatin or carboplatin were randomized to receive avelumab + BSC (n = 350) or BSC alone (n = 350).