Long-term responders to nivolumab in previously treated advanced renal cell carcinoma: a sub-analysis of meet-URO15 study.

BACKGROUND: Although nivolumab prolongs overall survival (OS) in pretreated patients with metastatic renal cell carcinoma (mRCC), underlining clinical and biological features of long-term responses are still to be determined. This study aims to investigate clinical and pathological characteristics of mRCC patients who achieved long-term responses during nivolumab treatment. MATERIALS AND METHODS: A retrospective analysis was performed on mRCC patients receiving nivolumab as second or further therapy line between May 2016 and January 2019 in 34 Italian Oncology Centres. Outcome assessments and logistic regression were performed to evaluate factors influencing long-term responses. RESULTS: A total of 571 patients with a median age of 61 years (range 17-85) were included in the analysis. With a median follow-up of 22.1 (1.0-89.0) months, 23.1% of patients were 2-year progression-free on treatment with nivolumab, hence they were categorized as long-term responders. Baseline characteristics, including age, gender, and histology, were similar between long- and short-term responders. Karnofsky Performance Status ≥ 80% was significantly associated with long-term response (p = 0.02), while bone metastases (p = 0.03), International mRCC Database Consortium intermediate-poor risk (p < 0.01) and Neutrophil-to-Lymphocyte Ratio ≥ 3.2 (p = 0.02) were associate with short-term responses. Long-term responders exhibited a median progression-free survival of 55.0 months versus 4.0 months of the short-term responders. The median OS was not reached in long-term responders while it was 17.0 months for short*term responders. CONCLUSION: This retrospective analysis sheds light on factors associated with long-term response to nivolumab in mRCC. Understanding these clinical features will be essential for selecting patients who may mostly benefit from immunotherapy.

The role of the caregiver in older patients with advanced prostate cancer: results from the ADHERE Prospective Study of the Meet-URO network.

PURPOSE: To assess caregivers' characteristics and influence of the presence or absence of the caregiver on clinical outcomes of older (≥70 years) metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone (ABI) or enzalutamide (ENZ). METHODS: Patients from the Meet-URO 5 ADHERE study were assessed with a 5-item caregiver evaluation questionnaire focusing on the presence, age, degree of kinship, working status and qualification of the caregiver. We investigated the association between the presence of a caregiver and the clinical characteristics and outcomes of enrolled patients. RESULTS: No differences were found in the main clinical characteristics between patients with or without a caregiver, except for a lower median G8 score (p = 0.0453) in the caregiver group. A longer radiographic PFS (rPFS) was observed in the group without a caregiver, with a trend towards more prolonged overall survival (OS) in the same group. CONCLUSION: Our work suggests a detrimental effect of caregivers in managing older mCRPC patients treated with ABI or ENZ, especially those identified as frail by the geriatric G8 screening score. Further work is needed to identify and address patients' vulnerability areas, which could have a detrimental effect on prognosis.

Pembrolizumab Plus Axitinib for Metastatic Papillary and Chromophobe Renal Cell Carcinoma: NEMESIA (Non Clear MEtaStatic Renal Cell Carcinoma Pembrolizumab Axitinib) Study, a Subgroup Analysis of I-RARE Observational Study (Meet-URO 23a).

Non-clear cell renal cell carcinoma (nccRCC) represents a heterogeneous histological group which is 20-25% of those with renal cell carcinoma (RCC). Patients with nccRCC have limited therapeutic options due to their exclusion from phase III randomized trials. The aim of the present study was to investigate the effectiveness and tolerability of pembrolizumabaxitinib combination in chromophobe and papillary metastatic RCC (mRCC) patients enrolled in the I-RARE (Italian Registry on rAre genitor-uRinary nEoplasms) observational ongoing study (Meet-URO 23). Baseline characteristics, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) and toxicities were retrospectively and prospectively collected from nccRCC patients treated in 14 Italian referral centers adhering to the Meet-Uro group, from December 2020 to April 2022. Only patients with chromophobe and papillary histology were considered eligible for the present pre-specified analysis. There were 32 eligible patients who received pembrolizumab-axitinib as first-line treatment, of whom 13 (40%) had chromophobe histology and 19 (60%) were classified as papillary RCC. The DCR was 78.1% whereas ORR was 43.7% (11 patients achieved stable disease and 14 patients obtained partial response: 9/19 papillary, 5/13 chromophobe). Six patients (18.7%) were primary refractory. Median PFS was 10.8 months (95%CI 1.7-11.5). Eleven patients (34.3%) interrupted the full treatment due to immune-related adverse events (irAEs): G3 hepatitis (n = 5), G3 hypophisitis (n = 1), G3 diarrhea (n = 1), G3 pancreatitis (n = 1), G3 asthenia (n = 1). Twelve patients (37.5%) temporarily interrupted axitinib only due to persistent G2 hand-foot syndrome or G2 hypertension. Pembrolizumab-axitinib combination could be an active and feasible first-line treatment option for patients with papillary or chromophobe mRCC.

Adherence to Oral Treatments in Older Patients with Advanced Prostate Cancer, the ADHERE Study: A Prospective Trial of the Meet-URO Network.

BACKGROUND: Novel androgen receptor signaling inhibitors for prostate cancer (PC) impose the burden of self-administration on older patients overwhelmed by the requirement of many other concomitant medications. PATIENTS AND METHODS: This study evaluated the proportion of non-adherence in a 12-month follow-up period and the first 3 months to abiraterone (ABI) or enzalutamide (ENZ). In a prospective multicenter observational cohort study, patients with metastatic castration-resistant PC (mCRPC) aged ≥70 years receiving ABI or ENZ pre- or post-docetaxel were enrolled. Treatment monitoring included pill counting, a self-assessment questionnaire, and clinical diaries at each clinical visit. Non-adherence rates were based on proportions of missed/prescribed pills ratios by pill counting. RESULTS: Overall, 234 patients were recruited with median age of 78 years (range, 73-82); 86 (37%) were treated with ABI, and 148 (63%) with ENZ. The median follow-up for adherence was seven monthly cycles (IQR: 4-12). The two cohorts were well balanced for baseline characteristics. The percentage of non-adherence by pill counting was slightly higher for ABI than ENZ (5.2% vs. 4.2%, P < .001). By self-reporting, patients on ENZ tended to report more frequently than those with ABI forgetfulness as the reason for missing events (42% vs. 17%, P < .001). A lower Geriatric G8 score correlated with non-adherence (P = .004). Overall survival (OS) was 48.8 months. Patients on ABI had radiographic progression-free survival (rPFS) of 28.4 [24.2-32.5], while for ENZ patients, we reported a median rPFS of 23.1 [18.2-28.1] months. CONCLUSION: Physicians tend to treat older mCRPC patients with ENZ. Non-adherence rate is relatively low overall but can be higher with ABI than with ENZ and correlates with the Geriatric G8 score. Forgetfulness is a potential barrier for ENZ.

The prognostic value of the previous nephrectomy in pretreated metastatic renal cell carcinoma receiving immunotherapy: a sub-analysis of the Meet-URO 15 study.

BACKGROUND: Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era. METHODS: We investigated the Meet-URO-15 study dataset of 571 pretreated mRCC patients receiving nivolumab as second or further lines about the prognostic role of the previous nephrectomy (received in either the localized or metastatic setting) in the overall population and according to the Meet-URO score groups. RESULTS: Patients who underwent nephrectomy showed a significantly reduced risk of death (HR 0.44, 95% CI 0.32-0.60, p < 0.001) with a longer median overall survival (OS) (35.9 months vs 12.1 months), 1-year OS of 71.6% vs 50.5% and 2-years OS of 56.5% vs 22.0% compared to those who did not. No significant interaction between nephrectomy and the overall five Meet-URO score risk groups was observed (p = 0.17). It was statistically significant when merging group 1 with 2 and 3 and group 4 with 5 (p = 0.038) and associated with a longer OS for the first three prognostic groups (p < 0.001), but not for groups 4 and 5 (p = 0.54). CONCLUSIONS: Our study suggests an overall positive impact of the previous nephrectomy on the outcome of pretreated mRCC patients receiving immunotherapy. The clinical relevance of cytoreductive nephrectomy, optimal timing and patient selection deserves further investigation, especially for patients with Meet-URO scores of 1 to 3, who are the once deriving benefit in our analyses. However, that benefit is not evident for IMDC poor-risk patients (including the Meet-URO score groups 4 and 5) and a subgroup of IMDC intermediate-risk patients defined as group 4 by the Meet-URO score.

Safety and Efficacy of Tivozanib in First-Line mRCC: A Multicenter Compassionate-Use Study (Meet-Uro 16).

INTRODUCTION: Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, and VEGFR-3, recently approved in Europe for the first-line treatment of metastatic renal cell carcinoma (mRCC). METHODS: Retrospective analysis of safety and activity of tivozanib administered at 1.34 mg daily (3 weeks on, 1 week off) within a compassionate-use program to patients with mRCC with no prior systemic treatment in Italy. RESULTS: From August 2018 to April 2019, 64 patients have started tivozanib in 9 oncology units. The median age was 67.5 years (range 40-85), 62.5% males. According to International Metastatic Renal Cell Carcinoma Database Consortium criteria, 27.1% of patients were good prognosis, 57.6% intermediate, and 15.3% poor. Primary tumor had been removed in 71.9% of patients. Histology was clear cell 89%, papillary 4.7%, and unclassified 6.3%. The response rate was 34.4%, stable disease 40.6%, and progression 15.6%. Grade 3-4 toxicities were 7.8% hypertension, 4.7% anemia, 3.1% mucositis, 3.1% asthenia, 1.6% diarrhea, 1.6% anorexia, 1.6% worsening of renal function, and 3.1% cardiac events. Dose reduction to 0.89 mg was applied to 17.2% of patients, and the discontinuation rate due to toxicity was 5.8%. Median progression-free survival was 12.4 months, with 68.7% of patients alive at 12 months. The developing of hypertension predicted increased progression-free survival at multivariate analysis (HR, 0.128; 95% CI, 0.03-0.59; p = 0.008). CONCLUSIONS: Tivozanib showed good activity and favorable safety profile in a real-world cohort of unselected patients with mRCC. Predictive biomarkers of response to antiangiogenic therapy are urgently needed in order to identify RCC patients who could still receive a monotherapy with VEGFR inhibitors in the first line.

Eribulin Mesylate as Third or Subsequent Line Chemotherapy for Elderly Patients with Locally Recurrent or Metastatic Breast Cancer: A Multicentric Observational Study of GIOGer (Italian Group of Geriatric Oncology)-ERIBE.

BACKGROUND: Metastatic breast cancer (MBC) is highly prevalent in middle-aged or elderly patients. Eribulin is a nontaxane microtubule inhibitor, approved for the treatment of pretreated MBC. This multicentric study (sponsored by GIOGer, Italian Group for Geriatric Oncology) was designed to assess the efficacy and tolerability of eribulin, according to parameters usually used in geriatric oncology. SUBJECTS, MATERIALS, AND METHODS: An observational study was conducted on 50 consecutive elderly patients with MBC. The primary endpoint was to evaluate the change in items score of comprehensive geriatric assessment (CGA) and health-related quality of life (HRQL). Italian versions of the CGA and HRQL questionnaires were administered at baseline, before the third and fifth cycles, and then every three cycles until treatment discontinuation. Secondary endpoints were efficacy and safety. RESULTS: Overall, both EQ-5D scores and EQ-5D-3 L visual analogic scale did not significantly change from baseline; the percentage of subjects without problems doing usual activities tended to decrease during treatment (p for linear trend .018), and the percentage of patients with minor problems performing usual activities tended to increase (p for linear trend.012). Among CGA items, Instrumental Activities of Daily Living tended to decrease during treatment and Geriatric Depression Scale tended to increase. After 12 months follow-up, 24 patients (out of 47) showed clinical benefits; median progression-free survival was 4.49 months (2.10-10.33) and median OS was 7.31 months (3.70-14.03). The treatment was associated with mild toxicity. CONCLUSION: Eribulin treatment preserved quality of life and geriatric parameters included in the CGA, except for instrumental functioning and geriatric depression, in elderly patients with MBC. IMPLICATIONS FOR PRACTICE: A collaboration between oncologist and geriatric specialists is essential in the management of patients with metastatic breast cancer, who are frequently elderly or frail. The assessment of geriatric parameters in the decision-making process can contribute to direct toward the most appropriate therapeutic plan and preserve the quality of life of patients. Eribulin does not seem to affect quality of life or worsen the overall geriatric status; therefore, it can be considered a suitable option for elderly patients with metastatic breast cancer.

Enzalutamide after chemotherapy in advanced castration-resistant prostate cancer: the Italian Named Patient Program.

AIM: To collect efficacy and safety data of enzalutamide after docetaxel, we retrospectively evaluated the Italian Named Patient Program results. PATIENTS & METHODS: Two hundred and nine metastatic castration-resistant prostate cancer patients were enrolled. Median age was 73 years. Total 42.1% patients had pain, 14.4% had a performance status of two and 59.8% had a Gleason score ≥8. Total 31.1% had previously received ≥2 chemotherapies, 15.3 and 12% had been previously treated with abiraterone and cabazitaxel, respectively and 14.8% had received both. RESULTS:  Median progression-free survival and overall survival were 4.8 and 13.1 months, respectively. A prostate-specific antigen reduction ≥50% was observed in 49.1%. Total 32.7% abiraterone-pretreated patients achieved a biochemical response compared with 56% of abiraterone-naive patients. CONCLUSION:  Enzalutamide was safe and well tolerated. Its antitumor activity in abiraterone-pretreated patients was limited.

Clinical outcomes in octogenarians treated with docetaxel as first-line chemotherapy for castration-resistant prostate cancer.

AIM: To assess clinical outcomes in octogenarians treated with docetaxel (DOC) for metastatic castration-resistant prostate cancer. PATIENTS & METHODS: The multicenter retrospective study was based on a review of the pre- and post-DOC clinical history, DOC treatment and outcomes. RESULTS: We reviewed the records of 123 patients (median age: 82 years) who received DOC every 3 weeks or weekly, without significant grade 3-4 toxicities. Median progression-free survival was 7 months; median overall survival from the start of DOC was 20 months, but post-progression treatments significantly prolonged overall survival. CONCLUSION: The findings of this study suggest that toxicity is acceptable, survival is independent of patient's age and survival can be significantly prolonged by the use of new agents.

Patient-Centered Cancer Care Programs in Italy: Benchmarking Global Patient Education Initiatives.

In Italy, educational programs for cancer patients are currently provided by the national government, scientific societies, and patient advocate organizations. Several gaps limit their effectiveness, including the lack of coordinated efforts, poor involvement of patient feedback in the planning of programs, as well as a lack of resources on innovative cancer-related topics. This process is parallel to a strong shift in the attitude of patients towards health in general and taking charge of their own health conditions in particular. The National Cancer Institute in the USA and the Organization of European Cancer Institutes encourage comprehensive cancer centers in providing educational programs conceived to overcome these gaps. The goal of this paper is to identify and describe the key elements necessary to develop a global patient education program and provide recommendations for strategies with practical examples for implementation in the daily activities of cancer institutes. A multidisciplinary committee was established for patient education, including patient representatives as equal partners, to define, implement, verify, and evaluate the fundamental steps for establishing a comprehensive education program. Six essential topics were identified for the program: appropriate communication of cancer epidemiology, clinical trial information, new therapeutic technologies, support in the use of medicines, psycho-oncological interventions, age-personalized approaches, and training programs for healthcare providers. Integration of these topics along with patient feedback is the key to a successful model for educational programs. An integrated educational program can transform a comprehensive cancer center to an institution that provides research and care for and with patients.

Metabolic syndrome in castration-resistant prostate cancer patients treated with abiraterone.

BACKGROUND: Metabolic syndrome (MS) has not yet been studied in castration-resistant prostate cancer (CRPC) men treated with novel hormonal therapies. The study aims to assess the impact of MS on outcome from time starting abiraterone. PATIENTS AND METHODS: We retrospectively evaluated a consecutive series of metastatic CRPC patients treated with abiraterone after docetaxel failure. MS, as defined by modified Adult Treatment Panel (ATP) III criteria, was assessed at the time of initiation of abiraterone, during treatment and follow-up. RESULTS: Sixty-seven of 178 patients evaluated (37.6%) met MS criteria at baseline, before abiraterone initiation, whereas for 11 (9.9%) without MS before treatment with abiraterone this occurred during treatment. Median PFS was equal to 4.7 months for patients with MS versus 9 months for those without MS. Patients with MS had an increased risk of 71% of progression or death for all causes than patients without MS (HR = 1.7, 95% CI [1.2-2.4], P = 0.03). Median OS was 14.7 months and 22.3 months in patients with and without MS, respectively. After adjusting for covariates, MS resulted not significantly associated to OS (HR = 1.42, 95% CI [0.91-2.22], P = 0.073). CONCLUSIONS: The presence of MS is a significant risk factor for shorter PFS in CRPC patients treated with abiraterone, even if it does not show a significant impact on OS. A prospective evaluation is warranted.

Safety and clinical outcomes of patients treated with abiraterone acetate after docetaxel: results of the Italian Named Patient Programme.

OBJECTIVE: To assess the safety and efficacy of abiraterone acetate (AA) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated in a compassionate named patient programme (NPP). PATIENTS AND METHODS: We retrospectively reviewed the clinical records of patients with mCRPC treated with AA at the standard daily oral dose of 1000 mg plus prednisone 10 mg/day in 19 Italian hospitals. RESULTS: We assessed 265 patients with mCRPC treated with AA. The most frequent (>1%) grade 3-4 toxicities were anaemia (4.2%), fatigue (4.2%), and bone pain (1.5%). The median progression-free survival was 7 months; median overall survival was 17 months after starting AA, and 35 months after the first docetaxel administration. Our study reproduced the clinical outcomes reported in the AA pivotal trial, including those relating to special populations such as the elderly, patients with a poor performance status, symptomatic patients, and patients with visceral metastases. CONCLUSIONS: Our data show the safety and activity of AA when administered outside clinical trials, and confirm the findings of the post-docetaxel pivotal trial in the patients as a whole population and in special populations of specific interest.

Intermittent docetaxel chemotherapy as first-line treatment for metastatic castration-resistant prostate cancer patients.

AIMS: The intermittent administration of chemotherapy is a means of preserving patients' quality of life (QL). The aim of this study was to verify whether the intermittent administration of docetaxel (DOC) improves the patients' QL. PATIENTS & METHODS: All patients received DOC 70 mg/m(2) every 3 weeks for eight cycles. The patients were randomized to receive DOC continuously or with a fixed 3-month interval after the first four DOC courses. RESULTS: The study involved 148 patients. There was no difference in QL between the groups receiving intermittent or continuous treatment. Intermittence had no detrimental effects on disease control. CONCLUSION: Although feasible and not detrimental, our results showed that true intermittent chemotherapy in metastatic castration-resistant prostate cancer patients failed to improve the patients' QL.

Impact of visceral metastases on outcome to abiraterone after docetaxel in castration-resistant prostate cancer patients.

BACKGROUND: The objective of this study was to analyze the impact of visceral metastases in castration-resistant prostate cancer (CRPC) treated with abiraterone. MATERIALS & METHODS: All CRPC patients received abiraterone 1000 mg daily plus prednisone 10 mg orally daily. Liver and lung metastases were considered as visceral metastases. RESULTS: Of 265 CRPC patients, 49 had visceral metastases. Results on progression-free survival were not significantly different in patients with or without visceral metastases. Conversely, the median overall survival between the two groups was 12.4 and 18.5 months (p = 0.01), respectively, and median overall survival of patients with liver-only disease versus other sites was 10.5 versus 18.5 months (p = 0.006), respectively. CONCLUSION: Visceral disease appears to be an important predictor of clinical outcome in CRPC patients treated with abiraterone.

Metabolomics biomarkers of frailty in elderly breast cancer patients.

Metabolome analysis has emerged as a powerful technique for detecting and define specific physio-pathological phenotypes. In this investigation the diagnostic potential of metabolomics has been applied to better characterize the multiple biochemical alterations that concur in the definition of the frailty phenotype observed in elderly breast cancer patients. The study included 89 women with breast cancer (range 70-97 years) classified as Fit (n = 49), Unfit (n = 23), or Frail (n = 17) according to comprehensive geriatric assessment. The serum metabolomic profile was performed by tandem mass spectrometry and included different classes of metabolites such as amino acids, acylcarnitines, sphingo-, and glycerol-phospolipids. ANOVA was applied to identify the metabolites differing significantly among Fit, Unfit, and Frail patients. In patients carrying the frail phenotype, the amino acid perturbations involve serine, tryptophan, hydroxyproline, histidine, its derivate 3-methyl-hystidine, cystine, and ß-aminoisobutyric acid. With regard to lipid metabolism, the frailty phenotype was characterized by a decrease of a wide number of glycerol- and sphingo-phospholipid metabolites. These metabolomics biomarkers may give a further insight into the biochemical processes involved in the development of frailty in breast cancer patients. Moreover, they might be useful to refine the comprehensive geriatric assessment model.

Real-world cabazitaxel safety: the Italian early-access program in metastatic castration-resistant prostate cancer.

AIM: Cabazitaxel is a novel taxane that is approved for use in metastatic castration-resistant prostate cancer based on the Phase III TROPIC study, which showed improved overall survival with cabazitaxel/prednisone versus mitoxantrone/prednisone. A global early-access program was initiated in order to provide early access to cabazitaxel in docetaxel-pretreated patients and to obtain real-world data. PATIENTS & METHODS: We report interim safety results from an Italian prospective, single-arm, multicenter, open-label trial of 218 patients receiving cabazitaxel 25 mg/m2 every 3 weeks plus prednisolone 10 mg/day, until disease progression, unacceptable toxicity, investigator's decision or death. RESULTS: Patients completing treatment received a median of six cabazitaxel cycles. The most common grade 3/4 adverse events were neutropenia (33.9%), leukopenia (15.6%), anemia (6%) and asthenia (6%). No peripheral neuropathy or nail disorders were observed. CONCLUSION: These results confirm that cabazitaxel has a manageable safety profile in daily clinical practice and support its use in patients with prostate cancer who progress during or after a docetaxel-based therapy.

Prognostic Stratification by the Meet-URO Score in Real-World Older Patients With Metastatic Renal Cell Carcinoma (mRCC) Receiving Cabozantinib: A Subanalysis of the Prospective ZEBRA Study (Meet-URO 9).

BACKGROUND: The addition of neutrophil to lymphocyte ratio (NLR) and bone metastases to the IMDC classification provided by the Meet-URO score, resulted in higher prognostic accuracy in metastatic renal cell carcinoma (mRCC) patients receiving ≥2nd line nivolumab or cabozantinib in 2 retrospective analyses and 1st line nivolumab-ipilimumab in an expanded access programme. Prognostic estimates for older mRCC patients might be key for clinical decision-making. METHODS: The outcome of real-world older (≥70 years) mRCC patients treated with any line cabozantinib within the multicenter observational prospective ZEBRA (Meet-URO 9) study was analyzed according to the baseline Meet-URO score. The primary endpoint was overall survival (OS). The discriminative ability by Harrell's c-index and calibration were assessed to compare the Meet-URO and IMDC scores. RESULTS: A total of 104 mRCC patients received cabozantinib as 1st (38%), 2nd (20%), or ≥3rd (41%) line. With a median follow-up of 11.2 months, the median OS (mOS) was of 18.4 months. According to the IMDC score, favorable (15%), intermediate (65%) and poor-risk (19%) patients had a mOS not reached, of 15.6 and 5.7 months respectively (p = .011). According to the Meet-URO score groups, mOS was not reached in both group 1 (10%) and group 2 (25%), while in group 3 (33%), group 4 (25%) and group 5 (8%) mOS was of 13.6, 12.5, and 3.7 months, respectively (p < .001). The discriminative ability of the Meet-URO score was maintained by merging groups 1 to 2 vs. 3 to 4 vs. 5 (p < .001). The Meet-URO score (with either the original 5-group stratification or the modified 3-group one) showed higher accuracy than the IMDC score (c-index of 0.686 and 0.676 vs. 0.622). CONCLUSION: This analysis confirmed the prognostic accuracy of the Meet-URO score in older mRCC patients treated with cabozantinib and its role as a convenient tool for informing the patient and clinical decisions.

A phase II study evaluating the efficacy of enzalutamide and the role of liquid biopsy for evaluation of ARv7 in mCRPC patients with measurable metastases including visceral disease (Excalibur study).

Background: Up to 30% of patients with metastatic castration-resistant prostate cancer (mCRPC) develop visceral metastases, which are associated with a poor prognosis. Objectives: Efficacy of enzalutamide in mCRPC patients with measurable metastases, including visceral and/or extra-regional lymph nodes. Methods: In this phase II multicenter study, patients with mCRPC and measurable metastases received enzalutamide as the first line. Primary endpoint: 3-month (mo) disease control rate (DCR) defined as the proportion of patients with complete (CR) or partial response (PR) or stable disease (SD) as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoint: safety. Exploratory endpoint: the association between ARv7 splicing variants in basal circulating tumor cell (CTC)-enriched blood samples and treatment response/resistance using the AdnaTest ProstateCancerSelect kit and the AdnaTest ProstateCancer Panel AR-V7. Results: From March 2017 to January 2021, 68 patients were enrolled. One patient never started treatment. Median age: 72 years. A total of 52 patients (78%) received enzalutamide as a first line for mCRPC. The median follow-up was 32 months. At the 3-month assessment, 24 patients presented an SD, 1 patient achieved a CR, and 23 patients had a PR (3-mo-DCR of 72%). Discontinuations due to adverse events (AEs), disease-related death, or disease progression occurred in 9%, 6%, and 48% of patients. All patients reported at least one grade (G) 1-2 AE: the most common were fatigue (49%) and hypertension (33%). Six G3 AEs were reported: two hypertension, one seizure, one fatigue, one diarrhea, and one headache. Basal detection of ARv7 was significantly associated with poor treatment response (p = 0.034) and a nonsignificant association (p = 0.15) was observed between ARv7 detection and response assessments. At month 3, ARv7 was detected in 57%, 25%, and 15% of patients undergoing progressive disease, SD, and PR, respectively. Conclusion: The study met its primary endpoint, showing the efficacy of enzalutamide in men with mCRPC and measurable metastatic lesions in visceral and/or lymph node sites. Trial registration: ClinicalTrials.gov Identifier: NCT03103724. First Posted: 6 April 2017. First patient enrollment: 19 April 2017.

Instrumental activities of daily living in older patients with metastatic prostate cancer: results from the meet-URO network ADHERE prospective study.

Instrumental activities of daily living (IADL) are significant health indicators closely related to executive functions and able to detect mild cognitive impairment. A decline in IADL usually precedes ADL limitation, including taking medications, and may therefore predict a cognitive decline. We aimed to investigate the association of patients' IADL score with other clinical factors, with a particular focus on the presence of a caregiver, and the impact on adherence to androgen receptor pathway inhibitors (ARPIs) and survival outcomes within the Meet-URO 5-ADHERE study. It was a large prospective multicentre observational cohort study monitoring adherence to ARPIs in 234 metastatic castrate-resistant PC (mCRPC) patients aged ≥ 70. We observed an association between impaired IADL and lower geriatric G8 scores (p < 0.01), and lower adherence to ARPIs whether assessed by pill counting (p = 0.01) or self-reported by the patient himself (p = 0.03). The combination of an IADL < 6 and the absence of a caregiver resulted in a significantly high risk of non-adherence to the ARPIs at the multivariable analysis (HR 9.23, 95% confidence interval 2.28-37.43, p = 0.01). IADL alongside the geriatric G8 scales represent essential tools to identify frail and less auto-sufficient patients who are extremely vulnerable particularly if not supported by a caregiver and have the highest risk of nonadherence to ARPIs.

Initial management approach for localized/locally advanced disease is critical to guide metastatic castration-resistant prostate cancer care.

BACKGROUND: Currently, several therapies are available for metastatic castration-resistant prostate cancer (mCRPC) but no specific clinical factors to personalize treatment. We first sought the prognostic value of duration on androgen-deprivation therapy (ADT) for hormone-sensitive prostate cancer (HSPC) in patients receiving androgen-receptor-signaling inhibitors (ARSI) for mCRPC. METHODS: A multicenter cohort of mCRPC patients who started ARSI between July 2011 and October 2021 was identified. Based on their initial disease burden and duration on ADT for HSPC, primary progressive (PP) men were classified into four groups: low/intermediate-risk localized disease (LOC) and high-risk localized/locally advanced disease (LAD) and short-term (ST) < 24 vs. long-term (LT) ADT ≥ 24 months, whereas de novo (DN) mHSPC were subdivided into short-time vs. long-time to CRPC. RESULTS: We included 919 mCRPC patients with a median age of 77 years [interquartile range (IQR) = 71-82)]. Median ADT duration in HSPC was 24 months (IQR = 14-40). Median follow-up was 91 months (IQR = 62-138), median OS and PFS from ARSI start were 20 (IQR 10-32) and 10 months (IQR = 5-19), respectively. In PP developing metastatic disease (n = 655, 71.3%), LOC and LAD with ST ADT had a greater than almost double-risk of death compared to LT ADT (LOC/ST: hazard ratio [HR] = 2.01; 95% CI 1.54-2.64; LAD/ST: HR = 1.73; 95% CI 1.34-2.24; p < 0.001). In the multivariate analysis including age, prognostic cohort, Gleason, ECOG, radical radiotherapy and prostatectomy, groups with ST ADT were associated with worse OS compared to LT ADT (LOC/ST: HR = 1.84; 95% CI 1.38-2.45; p < 0.001; LAD/ST: HR = 1.59; 95% CI 1.21-2.10; p < 0.001), along with ECOG > 2 (HR = 1.55; 95% CI 1.06-2.26; p = 0.03). There were also similar results of PFS. Moreover, long-time to CRPC in patients with history of DN mHSPC (n = 264, 28.7%) resulted in a better OS/PFS (HR = 0.76, 95% CI 0.56-1.02, p = 0.064 and HR = 0.74, 95% CI 0.55-0.99, p = 0.042, respectively). CONCLUSIONS: Our study showed that duration on ADT for mHSPC was significantly associated with survival in mCRPC undergoing ARSI. These findings suggest a possible connection between initial management of prostate tumour and a better prognostication in mCRPC. Prospective trials are warranted.