Publications by authors named "Vadim Koshkin"
Background: FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.
Patients And Methods: We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI.
Enfortumab vedotin (EV) is used as monotherapy or combined with pembrolizumab in advanced urothelial carcinoma (aUC), but biomarker data associated with EV outcomes are limited. We identified 170 patients in the UNITE study who received EV monotherapy and had molecular biomarker data available. Outcomes for groups with and without a particular biomarker were compared using logistic regression (unadjusted) for the objective response rate (ORR), and a log-rank test and Cox proportional-hazard models (CPHMs) for progression-free survival (PFS) and overall survival (OS) from EV initiation.
View Article and Find Full Text PDFArticle Synopsis
- - Patients with advanced/metastatic urothelial carcinoma who previously responded to or maintained stable disease with pembrolizumab immunotherapy may benefit from retreatment after disease progression, based on a post hoc analysis involving 49 patients from earlier clinical trials.
- - The study found that 41% of these patients achieved an objective response following retreatment, with a notable percentage having had a complete response during the initial treatment, and the median duration of the response was around 14 months.
- - Additionally, the retreatment led to manageable adverse effects, with only 45% experiencing treatment-related events, indicating that pembrolizumab retreatment is a viable and relatively safe option for select patients.
Introduction: Consultation audio recordings improve patient decision-making but are underutilized. Patient-administered recording apps on mobile devices may increase access, but implementation has not been evaluated.
Methods: We conducted a single-arm study delivering education, coaching, and reminders for patients to record their appointment using a mobile recording app.
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.
Association of Tumor Mutational Burden and Microsatellite Instability With Response and Outcomes in Patients With Urothelial Carcinoma Treated With Immune Checkpoint Inhibitor.
Clin Genitourin Cancer
December 2024
Article Synopsis
- - The study investigated the relationship between Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI) status in patients with urothelial carcinoma (UC) receiving immune checkpoint inhibitors (ICI), focusing on overall survival (OS).
- - Results showed that patients with a higher TMB (≥10 mut/Mb) generally experienced longer median OS compared to those with lower TMB, although these differences weren't always statistically significant.
- - Notably, patients treated with maintenance avelumab had a significantly better OS when TMB was high (61 months vs. 17 months for low TMB), indicating potential benefits of ICI based on TMB and MSI status, warranting further investigation.
Article Synopsis
- The study assessed the effectiveness of poly(ADP-ribose)polymerase inhibitors (PARPi) and platinum chemotherapy in men with prostate cancer (PC) and specific genetic mutations related to DNA repair.
- It utilized data from the PROMISE consortium to compare outcomes between three groups based on their mutation profiles: one with direct BRCA complex interactions and two without.
- Results showed that patients with BRCA mutations had significantly better responses to PARPi, including higher PSA response rates and longer progression-free survival, compared to those without direct BRCA interactions.
Background: [Lu]Lu-PSMA-617 (Lu-PSMA-617) plus protocol-permitted standard of care (SOC) prolonged overall survival (OS) and radiographic progression-free survival (rPFS) versus SOC in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 VISION study, in addition to beneficial effects on symptomatic skeletal events (SSEs) and health-related quality of life (HRQOL).
Methods: Post hoc analyses used the full analysis set from the VISION study (N = 831) overall and by randomized treatment arm (Lu-PSMA-617 plus SOC, n = 551; SOC, n = 280). Correlations were determined between OS and rPFS and between rPFS or OS and time to SSE or to worsening HRQOL (Functional Assessment of Cancer Therapy-Prostate [FACT-P] and 5-level EQ-5D [EQ-5D-5L]).
Clinical implications of Wnt pathway genetic alterations in men with advanced prostate cancer.
Prostate Cancer Prostatic Dis
July 2024
Article Synopsis
- Aberrant Wnt signaling is linked to advanced prostate cancer, but its genetic impact on patients is still uncertain.
- A study analyzed data from the PROMISE database, finding that 12.9% of patients had Wnt alterations which were associated with significantly higher rates of liver and lung metastases compared to those without these alterations.
- Despite the increased prevalence of other genetic mutations in Wnt-altered patients, there were no significant differences in overall survival or treatment outcomes between groups.
Purpose: Ga-PSMA-11 is recommended for the selection of patients for treatment in the package insert for Lu-PSMA-617. We aimed to compare imaging properties and post-treatment outcomes from radioligand therapy (RLT) of patients selected with Ga-PSMA-11 and F-DCFPyL.
Methods: We retrospectively evaluated 80 patients undergoing PSMA RLT, who had pretreatment imaging using either Ga-PSMA-11 or F-DCFPyL.
HER2, encoded by the ERBB2 gene, is an important druggable driver of human cancer gaining increasing importance as a therapeutic target in urothelial carcinoma (UC). The genomic underpinnings of HER2 overexpression in ERBB2 nonamplified UC are poorly defined. To address this knowledge gap, we investigated 172 UC tumors from patients treated at the University of California San Francisco, using immunohistochemistry and next-generation sequencing.
View Article and Find Full Text PDFThere is no clear standard-of-care treatment for patients with metastatic urothelial carcinoma following progression on enfortumab vedotin and pembrolizumab, although multiple regimens are available, including platinum-based chemotherapy, sacituzumab govitecan, and erdafitinib for selected patients. Clinical trials will be important in informing decisions on the best treatment.
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- The study looked at how often men with advanced prostate cancer get tested with a special method called next-generation sequencing (NGS) to find helpful information about their disease.
- They analyzed data from 1,597 patients and found that only 9% had more than one NGS test, often discovering new useful information on the second test.
- The results suggest that doing these tests more than once could help doctors make better treatment choices for men with advanced prostate cancer.
Clinical implications of AR alterations in advanced prostate cancer: a multi-institutional collaboration.
Prostate Cancer Prostatic Dis
February 2024
Article Synopsis
- The study investigates how alterations in the androgen receptor (AR) gene affect the treatment outcomes for patients with castration-resistant prostate cancer (CRPC) receiving androgen receptor-targeting agents (ARTA).
- Researchers analyzed data from the PROMISE database, looking at patients' genomic testing results in relation to their ARTA treatment timing and clinical outcomes.
- Findings indicate that AR amplifications correlate with a longer time to disease progression, highlighting the need for more in-depth studies to better understand these genomic alterations' impact on treatment responses.
Mechanisms of tyrosine kinase inhibitor resistance in renal cell carcinoma.
Cancer Drug Resist
December 2023
Renal cell carcinoma (RCC), the most prevalent type of kidney cancer, is a significant cause of cancer morbidity and mortality worldwide. Antiangiogenic tyrosine kinase inhibitors (TKIs), in combination with immune checkpoint inhibitors (ICIs), are among the first-line treatment options for patients with advanced RCC. These therapies target the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase pathway and other kinases crucial to cancer proliferation, survival, and metastasis.
View Article and Find Full Text PDFImproved imaging modalities are needed to accurately stage patients with muscle-invasive bladder cancer (MIBC) and metastatic urothelial carcinoma. Imaging with small-molecule ligands or inhibitors of fibroblast activation protein (FAP) is a promising modality that has demonstrated initial efficacy across a broad range of tumors. We present our experience with the novel FAP-peptide binder Ga-FAP-2286 in patients with MIBC.
View Article and Find Full Text PDFBackground And Objective: Neoadjuvant cisplatin-based chemotherapy prior to radical cystectomy (RC) improves overall survival (OS) in muscle-invasive bladder cancer (MIBC). However, many patients are cisplatin ineligible; therefore, new treatment options are needed. Nivolumab without/with lirilumab prior to RC was investigated in cisplatin-ineligible patients in this phase 1b trial (NCT03532451) to determine its safety/feasibility.
View Article and Find Full Text PDFTreatment options for patients with metastatic urothelial carcinoma ineligible for cisplatin-based chemotherapy have historically been limited. O'Donnell et al. recently reported the results of EV-103 Cohort K, leading to accelerated approval of enfortumab vedotin and pembrolizumab for cisplatin-ineligible patients and raising additional questions of how to best utilize this effective regimen.
View Article and Find Full Text PDFBackground: Checkpoint inhibitors have been shown to have limited activity in patients with metastatic castration-resistant prostate cancer. We aimed to determine whether a single dose of lutetium-177 [Lu]-prostate-specific membrane antigen (PSMA)-617 (Lu-PSMA-617) followed by maintenance pembrolizumab was safe and could induce durable clinical benefit.
Methods: We did an open-label, dose-expansion, phase 1 study at the University of California, San Francisco (San Fransisco, CA, USA).
Article Synopsis
- This study investigates the impact of COVID-19 on female patients with breast cancer, particularly focusing on underrepresented racial/ethnic populations from March 2020 to June 2021 in the US.
- The analysis included 1,383 patients, revealing that older age and certain racial/ethnic groups (such as Black and Asian American/Pacific Islanders) showed higher odds of severe COVID-19 outcomes.
- Key findings noted that factors like worse performance status, pre-existing health conditions, and active cancer significantly contributed to increased severity, while variables like Hispanic ethnicity and anti-cancer therapy type did not impact outcomes as much.
Importance: Black men have higher incidence and mortality from prostate cancer. Whether precision oncology disparities affect Black men with metastatic castration-resistant prostate cancer (mCRPC) is unknown.
Objective: To compare precision medicine data and outcomes between Black and White men with mCRPC.