Impact of DPP4 Inhibition on Survival in Patients With Metastatic Renal Cell Carcinoma and Type 2 Diabetes Mellitus.

Background: Dipeptidyl peptidase IV (DPP4) is a cell surface receptor that possesses numerous substrates implicated in tumor growth and metastasis. Prior studies have suggested an association between DPP4 inhibition and increased progression-free survival (PFS) and overall survival (OS) in colorectal and lung cancers but no benefit in breast or pancreatic cancers. However, no studies to date have explored the impact of DPP4 inhibitors (DPP4i) in patients with metastatic renal cell carcinoma (mRCC).

Abiraterone, Olaparib, or Abiraterone + Olaparib in First-Line Metastatic Castration-Resistant Prostate Cancer with DNA Repair Defects (BRCAAway).

Purpose: Deleterious germline/somatic homologous recombination repair mutations (HRRm) are present in ∼25% of patients with metastatic castration-resistant prostate cancer (mCRPC). Preclinically, poly(ADP-ribose) polymerase (PARP) inhibition demonstrated synergism with androgen receptor pathway (ARP)-targeted therapy. This trial evaluated the efficacy of ARP inhibitor versus PARP inhibitor versus their combination as first-line therapy in patients with mCRPC with HRRms.

Clinical and Genomic Features of Patients with Renal Cell Carcinoma and Advanced Chronic Kidney Disease: Analysis of a Multi-Institutional Database.

Background: Patients with advanced chronic kidney disease (ACKD) are at an increased risk of developing renal cell carcinoma (RCC), but molecular alterations in RCC specimens arising from ACKD and overall survival (OS) in affected patients are not well defined.

Patients And Methods: Using the Oncology Research Information Exchange Network (ORIEN) Total Cancer Care protocol, 296 consented adult patients with RCC and somatic tumor whole exome sequencing were included. Patients with ACKD were defined as those with serum creatinine ≥1.

Clinical Management of Advanced Prostate Cancer: Where Does Radiopharmaceutical Therapy Fit in the Treatment Algorithm?

Most men with newly appreciated metastatic prostate cancer are optimally treated with a backbone consisting of androgen receptor-directed therapy with or without taxane chemotherapy. Despite improvements in disease outcomes, prostate cancer remains an extremely heterogeneous disease with variable mechanisms of therapeutic resistance. As a result, it remains a leading cause of cancer-related death in men.

PrECOG PrE0807: A Phase 1b Feasibility Trial of Neoadjuvant Nivolumab Without and with Lirilumab in Patients with Muscle-invasive Bladder Cancer Ineligible for or Refusing Cisplatin-based Neoadjuvant Chemotherapy.

Background 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.

Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States.

Unlabelled: Bone pain is a well-known quality-of-life detriment for individuals with prostate cancer and is associated with survival. This study expands previous work into racial differences in multiple patient-reported dimensions of pain and the association between baseline and longitudinal pain and mortality. This is a prospective cohort study of individuals with newly diagnosed advanced prostate cancer enrolled in the International Registry for Men with Advanced Prostate Cancer (IRONMAN) from 2017 to 2023 at U.

PROMISE Registry: A prostate cancer registry of outcomes and germline mutations for improved survival and treatment effectiveness.

Background: Recently approved treatments and updates to genetic testing recommendations for prostate cancer have created a need for correlated analyses of patient outcomes data via germline genetic mutation status. Genetic registries address these gaps by identifying candidates for recently approved targeted treatments, expanding clinical trial data examining specific gene mutations, and understanding effects of targeted treatments in the real-world setting.

Methods: The PROMISE Registry is a 20-year (5-year recruitment, 15-year follow-up), US-wide, prospective genetic registry for prostate cancer patients.

Quality of life in the year after new diagnosis with advanced prostate cancer for Black and White individuals living in the US.

Purpose: To assess differences in baseline and longitudinal quality of life among Black and White individuals in the US with advanced prostate cancer.

Methods: Secondary analysis of data from the International Registry for Men with Advanced Prostate Cancer (IRONMAN) including US participants newly diagnosed with advanced prostate cancer and identifying their race as Black or White from 2017 to 2023. Participants completed the EORTC QLQ-C30 Quality of Life (QoL) Survey at study enrollment and every 3 months thereafter for up to 1 year of follow-up reporting 15 scale scores ranging from 0 to 100 (higher functioning and lower symptom scores represent better quality of life).

Updates to Advanced Prostate Cancer: AUA/SUO Guideline (2023).

Purpose: In 2022 the American Urological Association (AUA) requested an Update Literature Review (ULR) to incorporate new evidence generated since the 2020 publication of this guideline. The resulting 2023 Guideline Amendment addresses updated recommendations for patients with advanced prostate cancer.

Materials And Methods: The ULR addressed 23 of the original 38 guideline statements and included an abstract-level review of eligible studies published since the 2020 systematic review.

CD46 targeted Pb alpha particle radioimmunotherapy for prostate cancer treatment.

We recently identified CD46 as a novel prostate cancer cell surface antigen that shows lineage independent expression in both adenocarcinoma and small cell neuroendocrine subtypes of metastatic castration resistant prostate cancer (mCRPC), discovered an internalizing human monoclonal antibody YS5 that binds to a tumor selective CD46 epitope, and developed a microtubule inhibitor-based antibody drug conjugate that is in a multi-center phase I trial for mCRPC (NCT03575819). Here we report the development of a novel CD46-targeted alpha therapy based on YS5. We conjugated Pb, an in vivo generator of alpha-emitting Bi and Po, to YS5 through the chelator TCMC to create the radioimmunoconjugate, Pb-TCMC-YS5.

EphrinB2 Inhibition and Pembrolizumab in Metastatic Urothelial Carcinoma.

Purpose: Patients with metastatic urothelial carcinoma have poor prognosis after failure of standard first-line chemotherapy. Immune check point programmed death 1-programmed death ligand 1 antibodies have low response rates and thus there exists a major unmet need.

Materials And Methods: In this phase II trial, patients with metastatic urothelial carcinoma that recurred or progressed after platinum-based chemotherapy received soluble EphB4-human serum albumin (sEphB4-HSA) in combination with pembrolizumab.

Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results from an expansion cohort of a multicentre, open-label, phase 1b trial (COSMIC-021).

Background: Patients with metastatic castration-resistant prostate cancer have few treatment options after novel hormonal therapy (eg, abiraterone or enzalutamide). We aimed to evaluate cabozantinib, a tyrosine kinase inhibitor with immunomodulatory properties, in combination with the PD-L1 inhibitor atezolizumab in metastatic castration-resistant prostate cancer.

Methods: COSMIC-021 is an ongoing, multicentre, open-label, phase 1b study with a dose-escalation stage followed by tumour-specific expansion stages.

Association between baseline body mass index and survival in men with metastatic hormone-sensitive prostate cancer: ECOG-ACRIN CHAARTED E3805.

Background: E3805 (CHAARTED) is a phase 3 trial demonstrating improved survival for men with metastatic hormone-sensitive prostate cancer (mHSPC) randomized to treatment with docetaxel (D) and androgen-deprivation therapy (ADT) versus ADT alone. We assessed the association of baseline body mass index (BMI) and metformin exposure with quality of life (QOL) and prostate cancer outcomes including survival in patients enrolled in the CHAARTED study.

Methods: We performed a posthoc exploratory analysis of the CHAARTED trial of men with mHSPC randomized to treatment with ADT with or without D between 2006 and 2012.

Cabozantinib in Combination With Atezolizumab for Advanced Renal Cell Carcinoma: Results From the COSMIC-021 Study.

Purpose: COSMIC-021 is evaluating cabozantinib plus atezolizumab in patients with solid tumors. We report results from patients with advanced clear cell (cc) and non-clear cell (ncc) renal cell carcinoma (RCC).

Methods: This phase Ib study (NCT03170960) enrolled patients age ≥ 18 years with advanced RCC.

Effect of Cisplatin and Gemcitabine With or Without Berzosertib in Patients With Advanced Urothelial Carcinoma: A Phase 2 Randomized Clinical Trial.

Importance: Preclinical studies suggest that inhibition of single-stranded DNA repair by ataxia telangiectasia and Rad3 (ATR) may enhance the cytotoxicity of cisplatin, gemcitabine, and other chemotherapeutic agents. Cisplatin with gemcitabine remains the standard up-front therapy for treatment in patients with metastatic urothelial cancer.

Objective: To determine whether the use of the selective ATR inhibitor, berzosertib, could augment the activity of cisplatin with gemcitabine.

Randomized Phase III Trial of Gemcitabine and Cisplatin With Bevacizumab or Placebo in Patients With Advanced Urothelial Carcinoma: Results of CALGB 90601 (Alliance).

Purpose: The combination of gemcitabine and cisplatin (GC) is a standard therapy for metastatic urothelial carcinoma. Based on data that angiogenesis plays a role in urothelial carcinoma growth and progression, a randomized placebo-controlled trial was performed with the primary objective of testing whether patients treated with GC and bevacizumab (GCB) have superior overall survival (OS) than patients treated with GC and placebo (GCP).

Patients And Methods: Between July 2009 and December 2014, 506 patients with metastatic urothelial carcinoma without prior chemotherapy for metastatic disease and no neoadjuvant or adjuvant chemotherapy within 12 months were randomly assigned to receive either GCB or GCP.

Molecular Imaging of Prostate Cancer Targeting CD46 Using ImmunoPET.

Purpose: We recently identified CD46 as a novel therapeutic target in prostate cancer. In this study, we developed a CD46-targeted PET radiopharmaceutical, [Zr]DFO-YS5, and evaluated its performance for immunoPET imaging in murine prostate cancer models.

Experimental Design: [Zr]DFO-YS5 was prepared and its binding affinity for CD46 was measured.

Partial Response and Stable Disease Correlate with Positive Outcomes in Atezolizumab-treated Patients with Advanced Urinary Tract Carcinoma.

Background: The value of a complete response to immune checkpoint inhibitor treatment for urothelial cancer is well recognised, but less is known about long-term outcomes in patients with a partial response or the benefit of achieving disease stabilisation.

Objective: To determine clinical outcomes in patients with a partial response or stable disease on atezolizumab therapy for advanced urinary tract carcinoma (UTC).

Design, Setting, And Participants: Data were extracted from three prospective trials (IMvigor210 cohort 2, SAUL, and IMvigor211) evaluating single-agent atezolizumab therapy for platinum-pretreated advanced UTC.

Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART I.

Purpose: The summary presented herein represents Part I of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. Please refer to Part II for discussion of the management of castration-resistant disease.

Materials And Methods: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant.

Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART II.

Purpose: The summary presented herein represents Part II of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with castration-resistant disease. Please refer to Part I for discussion of the management of patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer.

Results: The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer.