Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy: the ARON-2 study.

BACKGROUND: Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. PATIENTS AND METHODS: Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Cox proportional hazards models were adopted to explore the presence of prognostic factors. RESULTS: In total, 836 patients were included: 544 patients (65%) received pembrolizumab after progression to first-line platinum-based chemotherapy in the metastatic setting (cohort A) and 292 (35%) after recurring within < 12 months since the completion of adjuvant or neoadjuvant chemotherapy (cohort B). The median follow-up time was 15.3 months. The median OS and the ORR were 10.5 months and 31% in the overall study population, 9.1 months and 29% in cohort A and 14.6 months and 37% in cohort B. At multivariate analysis, ECOG-PS ≥ 2, bone metastases, liver metastases and pembrolizumab setting (cohort A vs B) proved to be significantly associated with worst OS and PFS. Stratified by the presence of 0, 1-2 or 3-4 prognostic factors, the median OS was 29.4, 12.5 and 4.1 months (p < 0.001), while the median PFS was 12.2, 6.4 and 2.8 months, respectively (p < 0.001). CONCLUSIONS: Our study confirms that pembrolizumab is effective in the advanced UC real-world context, showing outcome differences between patients recurred or progressed after platinum-based chemotherapy.

Plain language summary of the results from the TALAPRO-2 study: Talazoparib plus enzalutamide versus placebo plus enzalutamide for patients with advanced prostate cancer.

WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from the TALAPRO-2 research study (also known as a clinical trial). The TALAPRO-2 study tested the combination of two medicines called talazoparib plus enzalutamide. This combination of medicines was used as the first treatment for adult patients with metastatic castration-resistant prostate cancer. The combination of talazoparib plus enzalutamide was compared with a placebo plus enzalutamide. WHAT IS METASTATIC CASTRATION-RESISTANT PROSTATE CANCER?: Metastatic castration-resistant prostate cancer is a type of cancer that starts in the prostate and has spread to other parts of the body. Castration-resistant means that the cancer continues to grow even when testosterone levels in the blood are reduced to very low levels. Taking medicines to lower testosterone levels in the blood is a standard treatment for men with advanced prostate cancer. WHAT ARE THE AIMS OF THE TALAPRO-2 TRIAL?: TALAPRO-2 looked at if combining talazoparib plus enzalutamide would increase the length of time patients lived before their cancer got worse or they died compared with a placebo plus enzalutamide. Researchers looked at how treatment affected the size and number of tumors and the length of time before patients needed to change to a new cancer medicine. Researchers also looked at any side effects patients had during the study. WHAT ARE THE KEY TAKEAWAYS?: A total of 805 patients with metastatic castration-resistant prostate cancer took part in the study. Compared with patients who took a placebo plus enzalutamide, the group of patients who took talazoparib plus enzalutamide had a 37% reduced risk of their cancer getting worse or dying. Some patients had tumors that at the start of the study could be measured with scans. Sixty-two percent of patients who took talazoparib plus enzalutamide had their tumors decrease or shrink to the point that they could no longer be seen on scans versus 44% of patients who took a placebo plus enzalutamide. Patients who took talazoparib plus enzalutamide were more likely to have a longer time before they needed to change to a new cancer medicine. The most common side effects of talazoparib plus enzalutamide were low levels of red blood cells (66% of patients) and neutrophils (36% of patients), and excessive tiredness or exhaustion (34% of patients).Clinical Trial Registration: NCT03395197 (TALAPRO-2) (ClinicalTrials.gov).

Expert Consensus Recommendations on the Management of Treatment-emergent Adverse Events Among Men with Prostate Cancer Taking Poly-ADP Ribose Polymerase Inhibitor + Novel Hormonal Therapy Combination Therapy.

BACKGROUND AND OBJECTIVE: Recent clinical trials have shown improvement in progression-free survival in men with metastatic prostate cancer (mPC) treated with combination poly-ADP ribose polymerase (PARP) inhibitors (PARPi) and novel hormonal therapy (NHT). Regulatory bodies in the USA, Canada, Europe, and Japan have recently approved this combination therapy for mPC. Common adverse events (AEs) include fatigue, nausea and vomiting, and anemia. Nuanced AE management guidance for these combinations is lacking. The panel objective was to develop expert consensus on AE management in patients with mPC treated with the combination PARPi + NHT. METHODS: The RAND/University of California Los Angeles modified Delphi Panel method was used. AEs were defined using the Common Terminology Criteria for Adverse Events. Twelve experts (seven medical oncologists, one advanced practice registered nurse, three urologists, and one patient advocate) reviewed the relevant literature; independently rated initial AE management options for the agent suspected of causing the AE for 419 patient scenarios on a 1-9 scale; discussed areas of agreement (AoAs) and disagreement (AoDs) at a March 2023 meeting; and repeated these ratings following the meeting. Second-round ratings formed the basis of guidelines. KEY FINDINGS AND LIMITATIONS: AoDs decreased from 41% to 21% between the first and second round ratings, with agreement on at least one management strategy for every AE. AoAs included the following: (1) continue therapy with symptomatic treatment for patients with mild AEs; (2) for moderate fatigue, recommend nonpharmacologic treatment, hold treatment temporarily, and restart at a reduced dose when symptoms resolve; (3) for severe nausea or any degree of vomiting where symptomatic treatment fails, hold treatment temporarily and restart at a reduced dose when symptoms resolve; and (4) for hemoglobin 7.1-8.0 g/dl and symptoms of anemia, hold treatment temporarily and restart at a reduced dose after red blood cell transfusion. CONCLUSIONS AND CLINICAL IMPLICATIONS: This expert guidance can support management of AEs in patients with mPC receiving combination PARPi + NHT therapy. PATIENT SUMMARY: A panel of experts developed guidelines for adverse event (AE) management in patients with metastatic prostate cancer treated with a combination of poly-ADP ribose polymerase inhibitors and novel hormonal therapy. For mild AEs, continuation of cancer therapy along with symptomatic treatment is recommended. For moderate or severe AEs, cancer therapy should be stopped temporarily and restarted at the same or a reduced dose when AE resolves.

Marital Status, Living Arrangement, and Survival among Individuals with Advanced Prostate Cancer in the International Registry for Men with Advanced Prostate Cancer.

BACKGROUND: Studies have shown improved survival among individuals with cancer with higher levels of social support. Few studies have investigated social support and overall survival (OS) in individuals with advanced prostate cancer in an international cohort. We investigated the associations of marital status and living arrangements with OS among individuals with advanced prostate cancer in the International Registry for Men with Advanced Prostate Cancer (IRONMAN). METHODS: IRONMAN is enrolling participants diagnosed with advanced prostate cancer (metastatic hormone-sensitive prostate cancer, mHSPC; castration-resistant prostate cancer, CRPC) from 16 countries. Participants in this analysis were recruited between July 2017 and January 2023. Adjusting for demographics and tumor characteristics, the associations were estimated using Cox regression and stratified by disease state (mHSPC, CRPC), age (<70, ≥70 years), and continent of enrollment (North America, Europe, Other). RESULTS: We included 2,119 participants with advanced prostate cancer, of whom 427 died during up to 5 years of follow-up (median 6 months). Two-thirds had mHSPC. Most were married/in a civil partnership (79%) and 6% were widowed. Very few married participants were living alone (1%), while most unmarried participants were living alone (70%). Married participants had better OS than unmarried participants [adjusted HR: 1.44; 95% confidence interval (CI): 1.02-2.02]. Widowed participants had the worst survival compared with married individuals (adjusted HR: 1.89; 95% CI: 1.22-2.94). CONCLUSIONS: Among those with advanced prostate cancer, unmarried and widowed participants had worse OS compared with married participants. IMPACT: This research highlighted the importance of social support in OS within this vulnerable population.

Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update.

PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.