Publications by authors named "Cora N Sternberg"
Article Synopsis
- The JAVELIN Bladder 100 trial demonstrated that avelumab, used as a first-line maintenance therapy, improves overall survival and progression-free survival in patients with advanced urothelial carcinoma after platinum-based chemotherapy.
- The PATRIOT-II study analyzed real-world outcomes of avelumab in 160 patients across various healthcare centers, emphasizing survival, safety, and resource use over a median follow-up of 16 months.
- Findings indicated a median progression-free survival of 5.4 months and overall survival of 24.4 months, with some patients experiencing treatment-related adverse effects, supporting the continued use of avelumab in similar patient populations.
Background: In the global ARASENS study (NCT02799602), darolutamide plus androgen-deprivation therapy (ADT) and docetaxel significantly reduced risk of death by 32.5% versus placebo plus ADT and docetaxel (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.
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- Innovations in advanced prostate cancer have improved outcomes, but there's still a lack of high-level evidence in clinical management, prompting the 2024 Advanced Prostate Cancer Consensus Conference to survey experts for insights.
- A panel of 120 international experts developed and voted on 183 consensus questions through a web-based survey prior to the conference, defining consensus as ≥75% agreement.
- The voting results highlight areas of agreement and disagreement that can guide clinical decisions and future research, with a focus on individualizing treatment based on patient characteristics and encouraging participation in clinical trials.
Article Synopsis
- Advanced urothelial cancer displays significant genetic diversity and involves complex interactions between internal and external mutagens, which contributes to its deadly nature.
- The study revealed that APOBEC3-induced mutations occur early during tumor development, while chemotherapy leads to a surge of later mutations, with both processes affecting the structure of extrachromosomal DNA.
- Findings emphasized the role of circular ecDNA in the development of treatment resistance, specifically through CCND1 amplifications, highlighting key mechanisms that can inform future cancer therapies.
Article Synopsis
- The review discusses the effectiveness of novel hormonal therapies (NHTs) and androgen receptor pathway inhibitors in treating castration-sensitive prostate cancer (CSPC), particularly in metastatic cases (mCSPC).
- Despite strong evidence showing that combining NHT with androgen deprivation therapy (ADT) extends life and improves quality of life, many patients are still only receiving single-agent ADT due to various barriers, including patient and physician misconceptions and access issues.
- For patients facing biochemical recurrence without metastasis, treatment strategies are being developed based on risk factors and characteristics, and early initiation of NHT may be beneficial for high-risk patients, alongside lifestyle management to counteract treatment side effects.
Purpose: Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate with an SN-38 payload, approved for patients with locally advanced (LA) or metastatic urothelial cancer (mUC) who progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report results from Cohort 2 of TROPHY-U-01 trial, evaluating the efficacy and safety of SG in patients with mUC.
Methods: TROPHY-U-01 (ClinicalTrials.
Background And Objective: Until recently, the standard first-line treatment for advanced urothelial carcinoma (UC) was platinum-based combination chemotherapy followed by avelumab maintenance therapy for patients without progressive disease (PD). For patients with advanced UC who experience PD or recurrence, standard-of-care treatment is pembrolizumab monotherapy based on the phase 3 KEYNOTE-045 study. This post hoc analysis of the KEYNOTE-045 study evaluated the efficacy of pembrolizumab compared with chemotherapy by the best response to prior platinum-based chemotherapy.
View Article and Find Full Text PDFPurpose: Human trophoblast cell surface antigen 2 (Trop-2) is a protein highly expressed in urothelial cancer (UC). Sacituzumab govitecan (SG) is a Trop-2-directed antibody drug conjugate with a hydrolysable linker and a potent SN-38 payload. This study explored Trop-2 expression in tumors treated with SG in cohorts 1 to 3 (C1-3) from the TROPHY-U-01 study and evaluated whether efficacy was associated with Trop-2 expression.
View Article and Find Full Text PDFBackground: Indoleamine 2,3-dioxygenase 1 (IDO1) levels correlate with poor outcomes in urothelial carcinoma (UC). IDO1 and programmed death-ligand 1 (PD-L1) are often co-expressed. Epacadostat is a potent and highly selective inhibitor of IDO1.
View Article and Find Full Text PDFBackground: The activity of PARP inhibitors (PARPi) in patients with homologous recombination repair (HRR) mutations and metastatic castration-resistant prostate cancer has been established. We hypothesized that the benefit of PARPi can be maintained in the absence of androgen deprivation therapy (ADT) in an HRR-mutated population. We report the results of a phase II clinical trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
View Article and Find Full Text PDFBackground: Defining optimal therapeutic sequencing strategies in prostate cancer (PC) is challenging and may be assisted by artificial intelligence (AI)-based tools for an analysis of the medical literature.
Objective: To demonstrate that INSIDE PC can help clinicians query the literature on therapeutic sequencing in PC and to develop previously unestablished practices for evaluating the outputs of AI-based support platforms.
Design, Setting, And Participants: INSIDE PC was developed by customizing PubMed Bidirectional Encoder Representations from Transformers.
Article Synopsis
- Atezolizumab was assessed for its safety in a diverse group of patients with pretreated urinary tract carcinoma (UTC) in the SAUL study, which included those typically excluded from clinical trials.
- The study involved 1004 patients and found that 68 patients continued treatment for over 4 years, with 16% experiencing serious treatment-related adverse events.
- Long-term results show a median overall survival of 8.6 months, with 14% of patients surviving more than 4 years, indicating the drug's potential benefits in real-world settings with complex patient profiles.
What Is This Summary About?: Sacituzumab govitecan (brand name: TRODELVY) is a new treatment being studied for people with a type of bladder cancer, called urothelial cancer, that has progressed to a locally advanced or metastatic stage. Locally advanced and metastatic urothelial cancer are usually treated with platinum-based chemotherapy. Metastatic urothelial cancer is also treated with immune checkpoint inhibitors.
View Article and Find Full Text PDFBackground And Objective: Addition of darolutamide to androgen deprivation therapy (ADT) and docetaxel significantly improved overall survival (OS) in ARASENS (NCT02799602). Here we report on prostate-specific antigen (PSA) responses and their association with outcomes.
Methods: ARASENS is an international, double-blind, phase 3 study in patients with metastatic hormone-sensitive prostate cancer (mHSPC) randomized to darolutamide 600 mg orally twice daily (n = 651) or placebo (n = 654), both with ADT + docetaxel.
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.
Article Synopsis
- Cancer of unknown primary (CUP) poses a major challenge, being a leading cause of cancer death despite better diagnostic methods.
- A novel genomic analysis using whole-exome sequencing (WES) and RNA sequencing (RNA-seq) helped tailor treatment for a patient with a history of multiple tumors and fast progression on chemotherapy.
- The approach resulted in significant improvements across all metastatic sites and underscores the need for personalized genomic profiling to effectively manage CUP and identify tumor origins.
Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3.
J Clin Oncol
April 2024
Purpose: Pembrolizumab is standard therapy for patients with metastatic urothelial cancer (mUC) who progress after first-line platinum-based chemotherapy; however, only approximately 21% of patients respond. Sacituzumab govitecan (SG) is a trophoblast cell surface antigen-2-directed antibody-drug conjugate with US Food and Drug Administration-accelerated approval to treat patients with locally advanced or mUC who previously received platinum-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report the primary analysis of TROPHY-U-01 cohort 3.
View Article and Find Full Text PDFBackground And Objective: BRCA2 mutations in metastatic castration-resistant prostate cancer (mCRPC) confer sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. However, additional factors predicting PARP inhibitor efficacy in mCRPC are needed. Preclinical studies support a relationship between speckle-type POZ protein (SPOP) inactivation and PARP inhibitor sensitivity.
View Article and Find Full Text PDFPurpose: Novel therapies are needed to extend survival in metastatic castration-resistant prostate cancer (mCRPC). Prostate-specific membrane antigen (PSMA), a cell surface antigen overexpressed in PC, provides a validated target. This dose-escalation study investigated the safety, efficacy, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) for Ac-J591, anti-PSMA monoclonal antibody J591 radiolabeled with the alpha emitter actinium-225.
View Article and Find Full Text PDFBackground: In the ARASENS trial (NCT02799602), darolutamide in combination with androgen-deprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5% (HR, 0.68; 95% CI, 0.
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