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Thromboembolic events (TE) are a common complication in patients with metastatic renal cell carcinoma (mRCC) and are associated with poorer clinical outcomes. However, the incidence of TE and clinical and genomic characteristics of patients with mRCC who develop this complication are poorly understood. Herein, we describe the incidence and clinical features of patients with mRCC with or without TE at our institution, and examine their association with the underlying genomic and transcriptomic characteristics of the tumor. This retrospective study included all consecutive cases of mRCC seen at our institution. A CLIA-certified lab performed tumor genomics and transcriptomics. Patients were classified based on the presence of a TE within the first year of diagnosis. Three hundred and seventy patients with mRCC were included in the study. TE was seen in 11% (42) of the patients. Patients with favorable International mRCC Database Consortium (IMDC) risk were less likely to develop a TE. In contrast, patients receiving combination treatment with a tyrosine kinase inhibitor (TKI) and an immune checkpoint inhibitor were more likely to develop a TE. No difference in overall survival among patients with or without TE was observed (52 vs. 55 months; HR 0.85, 95% CI 0.5574-1.293, p = 0.24). The most upregulated pathways in mRCC with TEs versus those without were the xenobiotic metabolism and mTORC1 signaling pathways. Our findings suggest potential biomarkers that, after external validation, could be used to better select patients who would benefit from prophylactic anticoagulation.
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The role of social determinants of health (SDOH) in controlling hypertension (HTN) in cancer patients is unknown. We hypothesize that high SDOH scores correlate with uncontrolled HTN in hypertensive cancer patients. In our prospective study patients completed the PRAPARE questionnaire. After integrating home and clinic blood pressure readings, uncontrolled HTN was defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg. Using Cox regression, we analyzed the impact of SDOH on HTN control, adjusting for relevant factors. The study involved 318 participants (median age 66.4, median follow-up 166 days, SDOH score 6.5 ± 3.2), with stress, educational insecurity, and social isolation as prevalent adverse SDOH. High SDOH scores led to 77% increased risk of uncontrolled HTN (aHR 1.77; 95% CI 1.10-2.83, p = .018). Urban residents with high SDOH scores were at an even greater risk. Identifying SDOH and mitigating underlying factors may help control HTN, the most typical disease process treated in all cardio-oncology clinics.
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PURPOSE: Deleterious germline/somatic homologous recombination-repair mutations (HRRm) are present in ~25% of metastatic castration resistant prostate cancer (mCRPC) patients. Preclinically, PARP-Inhibition demonstrated synergism with ARP-targeted therapy. This trial evaluated efficacy of ARP-Inhibitor versus PARP-Inhibitor versus combination as first-line therapy in mCRPC patients with HRRm. PATIENTS AND METHODS: BRCAAway is a biomarker pre-selected, randomized, phase-2 trial. Patients with BRCA1/2 and/or ATM alterations were randomized 1:1:1 to Arm1: Abiraterone (1000mg)/prednisone (Abi/pred) (5mg), Arm2: Olaparib (Ola) (300mg), or Arm3: Abiraterone/prednisone + Olaparib (Abi/pred+Ola). Single-agent arms could cross over at progression. Exploratory Arm4 patients with other HRRm received Olaparib alone. The primary endpoint was progression-free survival (PFS), and secondary endpoints were objective response, PSA response, and safety. RESULTS: 61/165 eligible patients had BRCA1/2 or ATM mutations: Median age: 67 (IQR 62-73) years. Mutations: BRCA1 n=3, BRCA2 n=46, ATM n=11, multiple n= 1; 33 germline, 28 somatic. Median PFS (95% CI): Abi/pred, 8.6 months (m) (2.9, 17), Ola, 14 m (8.4, 20), Abi/pred+Ola, 39 m (22, NR). There were no G4/5 AEs. 8/19 on Abi/pred crossed over to Ola, and 8/21 vice versa: Median PFS (95% CI) from crossover: Ola-after-Abi/pred, 8.3 m (5.5, 15); Abi/pred-after-Ola, 7.2 m (2.8, NR). Median PFS (95% CI) from randomization: Ola-after-Abi/pred, 16 m (7.8, 25), Abi/pred-after-Ola, 16 m (11, NR). 17/165 patients with other HRRm received olaparib: Median PFS (95% CI): 5.5 m (2, 11). CONCLUSIONS: In mCRPC patients with BRCA1/2 or ATM HRRm, abiraterone/prednisone + olaparib was well tolerated and demonstrated longer PFS versus either agent alone or sequentially.
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In the phase II FUZE trial targeting the FGFR pathway, Debio 1347 showed limited antitumor activity and manageable toxicity in patients with advanced solid tumors. Results from transcriptomic-based analysis enhanced our understanding of the genomic landscape of FGFR fusion-driven tumors, informing clinical trial design and generating hypotheses for resistance mechanisms.
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Importance: The presence of bone pain is significantly associated with worse overall survival (OS) in patients with castration-resistant prostate cancer. However, there are few data regarding bone pain and survival outcomes in the context of metastatic, hormone-sensitive prostate cancer (MHSPC). Objective: To compare survival outcomes among patients with MHSPC by presence or absence of baseline bone pain at diagnosis. Design, Setting, and Participants: This post hoc secondary analysis, conducted from September 1 to December 31, 2023, used patient-level data from SWOG-1216, a phase 3, prospective randomized clinical trial that enrolled patients with newly diagnosed MHSPC from 248 academic and community centers across the US from March 1, 2013, to July 15, 2017. All patients in the intention-to-treat population who had available bone pain status were eligible and included in this secondary analysis. Interventions: In the SWOG-1216 trial, patients were randomized (1:1) to receive either androgen deprivation therapy (ADT) with orteronel, 300 mg orally twice daily (experimental group), or ADT with bicalutamide, 50 mg orally daily (control group), until disease progression, unacceptable toxic effects, or patient withdrawal. Main Outcomes and Measures: Overall survival was the primary end point; progression-free survival (PFS) and prostate-specific antigen (PSA) response were secondary end points. Cox proportional hazards regression models were used for both univariable and multivariable analyses adjusting for age, treatment type, Gleason score, disease volume, Zubrod performance status, and PSA level. Results: Of the 1279 male study participants, 301 (23.5%) had baseline bone pain at MHSPC diagnosis and 896 (70.1%) did not. Bone pain status was unavailable in 82 patients (6.4%). The median age of the 1197 patients eligible and included in this secondary analysis was 67.6 years (IQR, 61.8-73.6 years). Compared with patients who did not experience bone pain, those with baseline bone pain were younger (median age, 66.0 [IQR, 60.1-73.4] years vs 68.2 [IQR, 62.4-73.7] years; P = .02) and had a higher incidence of high-volume disease (212 [70.4%] vs 373 [41.6%]; P < .001). After adjustment, bone pain was associated with shorter PFS and OS. At a median follow-up of 4.0 years (IQR, 2.5-5.4 years), patients with bone pain had median PFS of 1.3 years (95% CI, 1.1-1.7 years) vs 3.7 years (95% CI, 3.3-4.2 years) in patients without initial bone pain (adjusted hazard ratio [AHR], 1.46; 95% CI, 1.22-1.74; P < .001) and OS of 3.9 years (95% CI, 3.3-4.8 years) vs not reached (NR) (95% CI, 6.6 years to NR) in patients without initial bone pain (AHR, 1.66; 95% CI, 1.34-2.05; P < .001). Conclusions and Relevance: In this post hoc secondary analysis of the SWOG-1216 randomized clinical trial, patients with baseline bone pain at MHSPC diagnosis had worse survival outcomes than those without bone pain. These data suggest prioritizing these patients for enrollment in clinical trials, may aid patient counseling, and indicate that the inclusion of bone pain in prognostic models of MHSPC may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT01809691.
Subject(s)
Androgen Antagonists , Bone Neoplasms , Prostatic Neoplasms , Humans , Male , Aged , Androgen Antagonists/therapeutic use , Middle Aged , Prostatic Neoplasms/mortality , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/complications , Prostatic Neoplasms/pathology , Bone Neoplasms/secondary , Bone Neoplasms/mortality , Bone Neoplasms/complications , Bone Neoplasms/drug therapy , Nitriles/therapeutic use , Prospective Studies , Cancer Pain/drug therapy , Anilides/therapeutic use , Tosyl Compounds/therapeutic use , Tosyl Compounds/adverse effects , Androstenes/therapeutic use , Pain/drug therapy , Pain/etiologyABSTRACT
PURPOSE OF REVIEW: Analyze current evidence on racial/ethnic disparities in cardiovascular outcomes among cancer survivors, identifying factors and proposing measures to address health inequities. RECENT FINDINGS: Existing literature indicates that the Black population experiences worse cardiovascular outcomes following the diagnosis of both initial primary cancer and second primary cancer, with a notably higher prevalence of cardio-toxic events, particularly among breast cancer survivors. Contributing socioeconomic factors to these disparities include unfavorable social determinants of health, inadequate insurance coverage, and structural racism within the healthcare system. Additionally, proinflammatory epigenetic modification is hypothesized to be a contributing genetic variation factor. Addressing these disparities requires a multiperspective approach, encompassing efforts to address racial disparities and social determinants of health within the healthcare system, refine healthcare policies and access, and integrate historically stigmatized racial groups into clinical research. Racial and ethnic disparities persist in cardiovascular outcomes among cancer survivors, driven by multifactorial causes, predominantly associated with social determinants of health. Addressing these healthcare inequities is imperative, and timely efforts must be implemented to narrow the existing gap effectively.
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WHAT IS THIS SUMMARY ABOUT?: This summary is about the ongoing research study called TALAPRO-3. This study is testing the use of two medicines called talazoparib and enzalutamide. The two medicines are being used together as a treatment for patients with a type of cancer called metastatic castration-sensitive prostate cancer and changes in specific DNA repair genes within their tumors. The study began in May 2021, and includes 599 patients from 27 countries. WHAT IS METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER?: Metastatic castration-sensitive prostate cancer is known as mCSPC for short. It is cancer that has started in the prostate and spread to other body parts. The prostate is a gland below the bladder and helps make semen (the liquid that contains sperm). Castration-sensitive means that the cancer responds to treatments that lower testosterone in the blood. WHICH MEDICINES ARE BEING TESTED?: In this study, some patients will take talazoparib plus enzalutamide while others will take a placebo plus enzalutamide. Talazoparib and enzalutamide are two different cancer medicines. Talazoparib is not currently used to treat patients with mCSPC. Enzalutamide is used to treat patients with prostate cancer. Talazoparib plus enzalutamide is being compared with a placebo plus enzalutamide to see if patients live longer without their cancer getting worse, or them dying, when taking talazoparib plus enzalutamide or when taking a placebo plus enzalutamide. WHAT ARE THE AIMS OF THE TALAPRO-3 STUDY?: This study aims to find out if treatment with talazoparib plus enzalutamide increases the length of time the patients in the study live without their cancer getting worse, or them dying, compared with treatment with a placebo plus enzalutamide. The study will also measure how long the patients in the study live, the number and types of side effects they have, their general health and quality of life, and whether there are changes in how patients report their pain.Clinical Trial Registration: NCT03395197 (TALAPRO-2) (ClinicalTrials.gov).
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Importance: Targeted therapies based on underlying tumor genomic susceptible alterations have been approved for patients with metastatic prostate cancer (mPC) and advanced urothelial carcinoma (aUC). Objective: To assess trends and disparities in next-generation sequencing (NGS) testing among patients with mPC and aUC. Design, Setting, and Participants: This retrospective cohort study used an electronic health record-derived database to extract deidentified data of patients receiving care from US physician practices, hospital-affiliated clinics, and academic practices. Patients diagnosed with mPC or aUC between March 1, 2015, and December 31, 2022, were included. Exposures: Social determinants of health evaluated by race and ethnicity, socioeconomic status (SES), region, insurance type, and sex (for aUC). Main Outcomes and Measures: The primary outcomes were (1) NGS testing rate by year of mPC and aUC diagnosis using Clopper-Pearson 2-sided 95% CIs and (2) time to NGS testing, which considered death as a competing risk. Cumulative incidence functions were estimated for time to NGS testing. Disparities in subdistributional incidence of NGS testing were assessed by race and ethnicity, SES, region, insurance type, and sex (for aUC) using the Fine-Gray modified Cox proportional hazards model, assuming different subdistribution baseline hazards by year of mPC and aUC diagnosis. Results: A total of 11â¯927 male patients with mPC (167 Asian [1.6%], 1236 Black [11.6%], 687 Hispanic or Latino [6.4%], 7037 White [66.0%], and 1535 other [14.4%] among 10â¯662 with known race and ethnicity) and 6490 patients with aUC (4765 male [73.4%]; 80 Asian [1.4%], 283 Black [4.8%], 257 Hispanic or Latino [4.4%], 4376 White [74.9%], and 845 other [14.5%] among 5841 with known race and ethnicity) were eligible and included. Both cohorts had a median age of 73 years (IQR, 66-80 years), and most underwent NGS testing before first-line treatment in the mPC cohort (1502 [43.0%]) and before second-line treatment in the aUC cohort (1067 [51.3%]). In the mPC cohort, the rates of NGS testing increased from 19.0% in 2015 to 27.1% in 2022, but Black patients (hazard ratio [HR], 0.75; 95% CI, 0.67-0.84) and Hispanic or Latino patients (HR, 0.70; 95% CI, 0.60-0.82) were less likely to undergo NGS testing. Patients with mPC who had low SES (quintile 1: HR, 0.74 [95% CI, 0.66-0.83]; quintile 2: HR, 0.89 [95% CI, 0.80-0.99]), had Medicaid (HR, 0.53; 95% CI, 0.38-0.74) or Medicare or other government insurance (HR, 0.89; 95% CI, 0.82-0.98), or lived in the West (HR, 0.81; 95% CI, 0.70-0.94) also were less likely to undergo testing. In the aUC cohort, the NGS rate increased from 14.1% in 2015 to 46.6% in 2022, but Black patients (HR, 0.76; 95% CI, 0.61-0.96) and those with low SES (quintile 1: HR 0.77 [95% CI, 0.66-0.89]; quintile 2: HR, 0.87 [95% CI, 0.76-1.00]) or Medicaid (HR, 0.72; 95% CI, 0.53-0.97) or Medicare or other government insurance (HR, 0.88; 95% CI, 0.78-0.99) were less likely to undergo NGS testing. Patients with aUC living in the South were more likely to undergo testing (HR, 1.29; 95% CI, 1.12-1.49). Conclusions and Relevance: These findings suggest that although NGS tumor testing rates improved over time, the majority of patients still did not undergo testing. These data may help with understanding current disparities associated with NGS testing and improving access to standard-of-care health care services.
Subject(s)
Healthcare Disparities , High-Throughput Nucleotide Sequencing , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Retrospective Studies , Aged , High-Throughput Nucleotide Sequencing/methods , Middle Aged , Healthcare Disparities/statistics & numerical data , Female , United States/epidemiology , Urologic Neoplasms/genetics , Urologic Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Carcinoma, Transitional Cell/genetics , Aged, 80 and overABSTRACT
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).
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PURPOSE: Early PSA response has been found to be prognostic of outcomes in metastatic hormone sensitive prostate cancer. We performed a secondary analysis of the TITAN trial to determine if early PSA response was predictive of treatment efficacy in metastatic hormone sensitive prostate cancer patients. MATERIALS AND METHODS: Early PSA response was defined as achieving a PSA level of ≤ 0.2 ng/mL by 6 months of random assignment. A Cox proportional hazard model was constructed in a landmark population with an interaction term between the treatment and early PSA response to determine differential treatment effect on overall survival (OS). We applied multivariable Cox proportional hazard regression model with time to early PSA response fitted with restricted cubic spline to determine the association of time to early PSA response with OS. RESULTS: Approximately 24% (124/524) of patients in the androgen deprivation therapy (ADT) alone group and 61% (321/524) in the apalutamide group had PSA response ≤ 0.2 ng/mL by 6 months. Longer time to early PSA response was associated with significantly superior OS in the apalutamide group. There was a significant difference in treatment effect from apalutamide on OS (P = .03 for interaction) among 6-month PSA responders (HR: 0.66; 95% CI: 0.44-1.00) vs nonresponders (HR: 1.14; 95% CI: 0.89-1.46). This difference in treatment effect was not statistically significant at 3 months (P = .17 for interaction). Among 6-month PSA responders, 3-year confounder-adjusted OS was 84% (80%-88%) for the apalutamide group and 74% (66%-82%) for the ADT alone group. Among nonresponders, 3-year adjusted OS for the 2 treatment arms were 58% (52%-65%) and 56% (51%-60%), respectively. CONCLUSIONS: Early PSA response by 6 months was a predictor of treatment efficacy from ADT plus apalutamide on OS. Longer time to early PSA response was associated with superior OS in the apalutamide arm.
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OBJECTIVE: To assess the association between achievement of prostate-specific antigen (PSA) levels ≤0.2 ng/mL (henceforth 'ultralow') and clinical outcomes in patients in the 'Targeted Investigational Treatment Analysis of Novel Anti-androgen' (TITAN) study (ClinicalTrials.gov Identifier NCT02489318) with metastatic castration-sensitive prostate cancer (mCSPC). PATIENTS AND METHODS: Patients in the TITAN study with mCSPC were randomised to 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy. This post hoc analysis assessed the achievement of a PSA level of 0.2->0.02 ng/mL ('ultralow one' [UL1]) and ≤0.02 ng/mL ('ultralow two' [UL2]) vs >0.2 ng/mL with apalutamide treatment and its association with radiographic progression-free survival (rPFS), overall survival (OS), time to castration-resistant PC (TTCRPC), and time to PSA progression (TTPP). The landmark analysis and Kaplan-Meier methods were used. RESULTS: By 3 months, more patients achieved UL1 and UL2 with apalutamide (38% and 23%) vs placebo (15% and 5%). In the apalutamide-treated patients, UL2 vs PSA >0.2 ng/mL at landmark 3 months was associated with significantly longer rPFS (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.14-0.54), OS (HR 0.24, 95% CI 0.13-0.43), TTCRPC (HR 0.2, 95% CI 0.11-0.38), and TTPP (HR 0.11, 95% CI 0.04-0.27; nominal P values all <0.001); this association was also observed but less pronounced for UL1. Similar findings were observed at 6 months. Early onset of decline to UL2 by 3 months was associated with improved survival vs PSA >0.2 ng/mL anytime (HR 0.12, 95% CI 0.06-0.22; P < 0.001) in apalutamide-treated patients. CONCLUSIONS: In this post hoc analysis of TITAN, patients with the deepest PSA decline derived the greatest benefit. These results extend our findings of apalutamide efficacy in the overall TITAN population, underscoring the clinical value of PSA kinetics as a marker for treatment efficacy. PATIENT SUMMARY: Patients with metastatic prostate cancer that is sensitive to ongoing hormonal treatment benefited significantly from the addition of apalutamide compared with placebo. Those who achieved rapid and deep PSA reduction had the greatest survival benefit.
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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.
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BACKGROUND: The Life-Space Assessment (LSA) is an instrument that measures mobility in older adults as they reach different areas, defined as life-spaces extending from home to beyond towns or regions. The purpose of the study was to develop the Hindi version of the LSA (LSA- H) and to investigate the validity and reliability of the Hindi version as well as its cultural adaptation. METHODS: A cross-sectional study of two hundred forty-five older adults participated in the study from four different study practice areas. Following forward backwards translation, the LSA-H was developed, and the scores were correlated with those of the Activities-Specific Balance Confidence Scale Hindi (ABC- H), the Physical Health Subscale of the WHO-BREF Questionnaire and the Geriatric Depression Scale: Short Form Hindi (GDS-SFH) to test the criterion and concurrent validity. RESULTS: The mean score and standard deviation of the LSA-H questionnaire were 56.53 ± 35.99, those of the Physical Health Subscale of the WHO-BREF instrument were 18.54 ± 7.87, those of the GDS-SFH questionnaire were 6.95 ± 4.21 and those of the ABC- H questionnaire were 54.40 ± 28.96. The Pearson correlation coefficient (r) between the LSA-H score and ABC-H score was 0.707 (p value < 0.0001), that between the LSA-H score and the Physical Health Subscale of the WHO-BREF was 0.766 (p value < 0.0001), and that between the LSA-H score and GDS-SFG score was - 0.674 (p value < 0.0001). CONCLUSION: This study demonstrated that the Hindi version of the LSA is a valid and reliable instrument for assessing living space among older adults in the Hindi language in an Indian population. Furthermore, the LSA-H was significantly correlated with other health assessment tools in terms of functional mobility, general health status and mental well-being.
Subject(s)
Geriatric Assessment , Independent Living , Humans , Cross-Sectional Studies , Aged , Male , Female , Geriatric Assessment/methods , India , Aged, 80 and over , Activities of Daily Living/psychology , Surveys and Questionnaires/standards , Reproducibility of Results , Middle AgedABSTRACT
PURPOSE: Bempegaldesleukin (BEMPEG) is a pegylated interleukin (IL)-2 cytokine prodrug engineered to provide controlled and sustained activation of the clinically validated IL-2 pathway, with the goal of preferentially activating and expanding effector CD8+ T cells and natural killer cells over immunosuppressive regulator T cells in the tumor microenvironment. The open-label, phase III randomized controlled PIVOT-09 trial investigated the efficacy and safety of BEMPEG plus nivolumab (NIVO) as first-line treatment for advanced/metastatic clear cell renal cell carcinoma (ccRCC) with intermediate-/poor-risk disease. METHODS: Patients with previously untreated advanced/metastatic ccRCC were randomly assigned (1:1) to BEMPEG plus NIVO, or investigator's choice of tyrosine kinase inhibitor (TKI; sunitinib or cabozantinib). Coprimary end points were objective response rate (ORR) by blinded independent central review and overall survival (OS) in patients with International Metastatic RCC Database Consortium (IMDC) intermediate-/poor-risk disease. RESULTS: Overall, 623 patients were randomly assigned to BEMPEG plus NIVO (n = 311) or TKI (n = 312; sunitinib n = 225, cabozantinib n = 87), of whom 514 (82.5%) had IMDC intermediate-/poor-risk disease. In patients with IMDC intermediate-/poor-risk disease, ORR with BEMPEG plus NIVO versus TKI was 23.0% (95% CI, 18.0 to 28.7) versus 30.6% (95% CI, 25.1 to 36.6; difference, -7.7 [95% CI, -15.2 to -0.2]; P = .0489), and median OS was 29.0 months versus not estimable (hazard ratio, 0.82 [95% CI, 0.61 to 1.10]; P = .192), respectively. More frequent all-grade treatment-related adverse events (TRAEs) with BEMPEG plus NIVO versus TKI included pyrexia (32.6% v 2.0%) and pruritus (31.3% v 8.8%). Grade 3/4 TRAEs were less frequent with BEMPEG plus NIVO (25.8%) versus TKI (56.5%). CONCLUSION: First-line BEMPEG plus NIVO for advanced/metastatic ccRCC did not improve efficacy in patients with intermediate-/poor-risk disease but led to fewer grade 3/4 TRAEs versus TKI.
Subject(s)
Anilides , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Renal Cell , Kidney Neoplasms , Nivolumab , Polyethylene Glycols , Pyridines , Sunitinib , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Anilides/administration & dosage , Anilides/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Female , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Nivolumab/administration & dosage , Nivolumab/therapeutic use , Nivolumab/adverse effects , Aged , Pyridines/administration & dosage , Pyridines/therapeutic use , Sunitinib/therapeutic use , Sunitinib/administration & dosage , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Adult , Interleukin-2/administration & dosage , Interleukin-2/therapeutic use , Interleukin-2/adverse effects , Interleukin-2/analogs & derivatives , Aged, 80 and overABSTRACT
Aim: To describe overall survival, time to castration resistance and castration resistance-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) initiating apalutamide in a US oncology network. Patients & methods: Patients with mCSPC initiating apalutamide on or after 17 September 2019 from an electronic health record-derived deidentified database were included. Patients were followed from apalutamide initiation and were censored at the earlier of end of clinical activity or data availability (31 October 2022). Results: At 12 and 24 months, overall survival rates were 91.0 and 88.3%, rates of castration sensitivity were 85.7 and 72.1%, and castration resistance-free survival rates were 80.2 and 65.9%, respectively. Conclusion: Real-world clinical outcomes of patients with mCSPC treated with apalutamide were comparable to results from the phase III TITAN trial.
This study looked at health outcomes among 176 patients receiving a prostate cancer medication, apalutamide. The average age of patients was 72 years, and approximately two-thirds of patients were White. Two years after starting apalutamide, most patients remained alive and their cancer did not progress.
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Metastatic urinary tract cancer (mUTC) is challenging to treat in older adults due to comorbidities. We compared the clinical courses of younger and older (≥70 years) adults with mUTC receiving first-line (1L) systemic therapy in a tertiary cancer center. Baseline clinical characteristics, treatments received, tolerability, and survival outcomes were analyzed. Among 212 patients (103 older vs. 109 younger), the older patients had lower hemoglobin at baseline (84% vs. 71%, p = 0.03), the majority were cisplatin-ineligible (74% vs. 45%, p < 0.001), received more immunotherapy-based treatments in the 1L (52% vs. 36%, p = 0.01), received fewer subsequent lines of treatment (median 0 vs. 1, p = 0.003), and had lower clinical trial participation (30% vs. 18%, p = 0.05) compared to the younger patients. When treated with 1L chemotherapy, older patients required more dose adjustments (53.4% vs. 23%, p = 0.001) and received fewer cycles of chemotherapy (median 4 vs. 5, p= 0.01). Older patients had similar OS (11.2 months vs. 14 months, p = 0.06) and similar rates of treatment-related severe toxicity and healthcare visits, independent of the type of systemic treatment received, compared to younger patients. We conclude that select older adults with mUTC can be safely treated with immunotherapy and risk-adjusted regimens of chemotherapy with tangible survival benefits.
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BACKGROUND AND OBJECTIVE: EVEREST is a phase 3 trial in patients with renal cell cancer (RCC) at intermediate-high or very high risk of recurrence after nephrectomy who were randomized to receive adjuvant everolimus or placebo. Longer recurrence-free survival (RFS) was observed with everolimus (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.72-1.00; p = 0.051), but the nominal significance level (p = 0.044) was not reached. To contextualize these results with positive phase 3 trials of adjuvant sunitinib and pembrolizumab, we conducted a secondary analysis in a similar population of EVEREST patients with very high-risk disease and clear cell histology. METHODS: Postnephrectomy patients with any clear cell component and very high-risk disease, defined as pT3a (grade 3-4), pT3b-c (any grade), T4 (any grade), or node-positive status (N+), were identified. A Cox regression model stratified by performance status was used to compare RFS and overall survival (OS) between the treatment arms. KEY FINDINGS AND LIMITATIONS: Of 1499 patients, 717 had clear cell histology and very high-risk disease; 699 met the eligibility criteria, of whom 348 were randomized to everolimus arm, and 351 to the placebo arm. Patient characteristics were similar between the arms. Only 163/348 (47%) patients in the everolimus arm completed all treatment as planned, versus 225/351 (64%) in the placebo arm. Adjuvant everolimus resulted in a statistically significant improvement in RFS (HR 0.80; 95%CI 0.65-0.99, p = 0.041). Evidence of a survival benefit was not seen (HR 0.85; 95%CI 0.64-1.14, p = 0.3) CONCLUSIONS AND CLINICAL IMPLICATIONS: In patients with clear cell RCC at very high-risk for recurrence, adjuvant everolimus resulted in significantly improved RFS compared to placebo but resulted in a high discontinuation rate due to adverse events. Although the treatment HR for OS was consistent with RFS findings, it did not reach statistical significance. With a focus on risk stratification tools and/or biomarkers to minimize toxicity risk in those not likely to benefit, this information can help inform the design of future adjuvant trials in high-risk RCC PATIENT SUMMARY: We assessed treatment with everolimus in comparison to placebo after complete surgical removal of clear-cell kidney cancer at very high risk of recurrence. We found that survival outcomes were better for patients treated with everolimus, although these patients had a higher rate of side effects.
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Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.
Subject(s)
Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/therapy , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/pathology , Male , Neoplasm Staging , BCG Vaccine/therapeutic useABSTRACT
BACKGROUND AND OBJECTIVE: It has been reported that patients with de novo metastatic castration-sensitive prostate cancer (dn-mCSPC) have worse prognosis and outcomes than those whose cancer relapses after prior local therapy (PLT-mCSPC). Our aim was to interrogate and validate underlying differences in tumor gene expression profiles between dn-mCSPC and PLT-mCSPC. METHODS: The inclusion criteria were histologically confirmed prostate adenocarcinoma and the availability of RNA sequencing data for treatment-naïve primary prostate tissue. RNA sequencing was performed by Tempus or Caris Life Sciences, both of which have Clinical Laboratory Improvement Amendments certification. The Tempus cohort was used for interrogation, while the Caris cohort was used for validation. Differential gene expression analysis between the cohorts was conducted using the DEseq2 pipeline. The resulting gene expression profiles were further analyzed using Gene Set Enrichment software to identify pathways with enrichment in each cohort. KEY FINDINGS AND LIMITATIONS: Overall, 128 patients were eligible, of whom 78 were in the Tempus cohort (dn-mCSPC 37, PLT-mCSPC 41) and 50 were in the Caris cohort (dn-mCSPC 30, PLT-mCSPC 20). Tumor tissues from patients with dn-mCSPC had higher expression of genes associated with inflammation pathways, while tissues from patients with PLT-mCSPC had higher expression of genes involved in oxidative phosphorylation, fatty acid metabolism, and androgen response pathways. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study revealed upregulation of distinct genomic pathways in dn-mCSPC in comparison to PLT-mCSPC. These hypothesis-generating data could guide personalized therapy for men with prostate cancer and explain different survival outcomes for dn-mCSPC and PLT-mCSPC. PATIENT SUMMARY: We measured gene expression levels in tumors from patients with metastatic castration-sensitive prostate cancer. In patients with metastatic disease at first diagnosis, inflammatory pathways were upregulated. In patients whose metastasis occurred on relapse after treatment, androgen response pathways were upregulated. These findings could help in personalizing therapy for prostate cancer and explaining differences in survival.
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Purpose: Castration-sensitive prostate cancer (CSPC) is a complex and heterogeneous condition encompassing a range of clinical presentations. As new approaches have expanded management options, clinicians are left with myriad questions and controversies regarding the optimal individualized management of CSPC. Materials and Methods: The US Prostate Cancer Conference (USPCC) multidisciplinary panel was assembled to address the challenges of prostate cancer management. The first annual USPCC meeting included experts in urology, medical oncology, radiation oncology, and nuclear medicine. USPCC co-chairs and session moderators identified key areas of controversy and uncertainty in prostate cancer management and organized the sessions with multidisciplinary presentations and discussion. Throughout the meeting, experts responded to questions prepared by chairs and moderators to identify areas of agreement and controversy. Results: The USPCC panel discussion and question responses for CSPC-related topics are presented. Key advances in CSPC management endorsed by USPCC experts included the development and clinical utilization of gene expression classifiers and artificial intelligence (AI) models for risk stratification and treatment selection in specific patient populations, the use of advanced imaging modalities in patients with clinically localized unfavorable intermediate or high-risk disease and those with biochemical recurrence, recommendations of doublet or triplet therapy for metastatic CSPC (mCSPC), and consideration of prostate and/or metastasis-directed radiation therapy in select patients with mCSPC. Conclusions: CSPC is a diverse disease with many therapeutic options and the potential for adverse outcomes associated with either undertreatment or overtreatment. Future studies are needed to validate and clinically integrate novel technologies, including genomics, AI, and advanced imaging, to optimize outcomes among patients with CSPC.