Search

Objectives: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)‐Friends of Cancer Research (FCR) initiative. Methods: vPhase I–III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi‐square test were used to calculate their associations with certain trial characteristics. Results: A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively. Conclusion: A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO‐FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real‐world. [ABSTRACT FROM AUTHOR]

Background: Tertiary cancer centers offer clinical expertise and multi-modal approaches to treatment alongside the integration of research protocols. Nevertheless, most patients receive their cancer care at community practices. A better understanding of the relationships between tertiary and community practice environments may enhance collaborations and advance patient care. Methods: A 31-item survey was distributed to community and tertiary oncologists in Southern California using REDCap. Survey questions assessed the following attributes: demographics and features of clinical practice, referral patterns, availability and knowledge of clinical trials and precision medicine, strategies for knowledge acquisition, and integration of community and tertiary practices. Results: The survey was distributed to 98 oncologists, 85 (87%) of whom completed it. In total, 52 (61%) respondents were community practitioners and 33 (38%) were tertiary oncologists. A majority (56%) of community oncologists defined themselves as general oncologists, whereas almost all (97%) tertiary oncologists reported a subspecialty. Clinical trial availability was the most common reason for patient referrals to tertiary centers (73%). The most frequent barrier to tertiary referral was financial considerations (59%). Clinical trials were offered by 97% of tertiary practitioners compared to 67% of community oncologists (p = 0.001). Most oncologists (82%) reported only a minimal-to-moderate understanding of clinical trials available at regional tertiary centers. Conclusions: Community oncologists refer patients to tertiary centers primarily with the intent of clinical trial enrollment; however, significant gaps exist in their knowledge of trial availability. Our results identify the need for enhanced communication and collaboration between community and tertiary providers to expand patients’ access to clinical trials. [ABSTRACT FROM AUTHOR]

Background: Cabozantinib is approved for metastatic renal cell carcinoma (mRCC) based on the METEOR and CABOSUN trials. However, real‐world effectiveness and dosing patterns of cabozantinib are not well characterized. Methods: Patients with mRCC treated with cabozantinib between 2011 and 2019 were identified and stratified using the International mRCC Database Consortium (IMDC) risk groups. First‐ (1L), second‐ (2L), third‐ (3L), and fourth‐line (4L) overall response rate (ORR), time to treatment failure (TTF), and overall survival (OS) were analyzed. Dose reduction rates and their association with TTF and OS were determined. Results: A total of 413 patients were identified. The ORRs across 1L to 4L were 32%, 26%, 25%, and 29%, respectively, and the median TTF rates were 8.3, 7.3, 7.0, and 8.0 months, respectively. The median OS (mOS) rates in 1L to 4L were 30.7, 17.8, 12.6, and 14.9 months, respectively. For patients treated with 1L PD(L)1 combination agent (n = 31), 2L cabozantinib had ORR of 22%, median TTF of 5.4 months, and mOS of 17.4 months. About 50% (129/258) of patients required dose reductions. The TTF and mOS were significantly longer for patients who required dose reduction vs. patients who did not, with an adjusted hazard ratio of 0.37 (95% CI 0.202–0.672, p < 0.01) and 0.46 (95% CI 0.215–0.980, p = 0.04), respectively. Limitations include the retrospective study design and the lack of central radiology review. Conclusion: The ORR and TTF of cabozantinib were maintained from the 1L to 4L settings. Dose reductions due to toxicity were associated with improved TTF and OS. Cabozantinib has clinical activity after 1L Immuno‐oncology combination agents. [ABSTRACT FROM AUTHOR]

Background: Patient‐reported outcomes have been used to assess treatment effectiveness and actively engage patients in their disease management. This study was designed to describe the patient‐reported performance status (PS) and the provider‐reported PS. Methods: Patients with metastatic genitourinary cancers were recruited from a single cancer center before the initiation of a new line of treatment. PS (Eastern Cooperative Oncology Group [ECOG]), quality of life (Functional Assessment of Chronic Illness Therapy–General), and distress (Patient‐Reported Outcomes Measurement Information System Anxiety and Depression) were self‐reported by patients. Clinical data (eg, age, sex, diagnosis, and physician‐reported ECOG PS) were extracted from medical records. Multivariate analysis was used to determine the association between PS, quality of life, and psychological symptoms. Results: One hundred forty‐five patients were enrolled (76.6% male, 70.3% White, 81.4% married, and 76.6% well educated). The median age was 67 years; 66.9% were diagnosed with renal cell carcinoma, 20.0% were diagnosed with urothelial carcinoma, and 13.1% were diagnosed with prostate cancer. Clinicians more frequently classified patients' ECOG PS as 0 in comparison with the patients themselves (92.4% vs 64.1%; P =.001). Higher clinician‐reported ECOG PS was associated with poorer physical and functional well‐being and higher rates of depression (P <.01), whereas higher patient‐reported ECOG PS was associated with worse psychosocial outcomes (P <.01). Conclusions: Discrepancies were noted between the patient‐ and provider‐reported ECOG PS, with clinicians overestimating the ECOG PS in comparison with the patients themselves. This study's findings suggest that patients incorporate their social and emotional well‐being into their PS score in addition to their physical well‐being. This information is not immediately accessible to most clinicians from just a standard patient interview and likely accounts for the overestimation of the patients' ECOG PS by the clinicians. Clinicians appear to overestimate the Eastern Cooperative Oncology Group performance status in comparison with patients' self‐ratings. This study shows that the clinician‐reported performance status is unrelated to patients' ratings of their social/family well‐being and anxiety symptoms. [ABSTRACT FROM AUTHOR]

Studies suggest a link between the gut microbiome and metastatic renal cell carcinoma (mRCC) outcomes, including evidence that mRCC patients possess a lower abundance of Bifidobacterium spp. compared to healthy adults. We sought to assess if a Bifidobacterium‐containing yogurt product could modulate the gut microbiome and clinical outcome from vascular endothelial growth factor‐tyrosine kinase inhibitors (VEGF‐TKIs). mRCC patients initiating VEGF‐TKIs, regardless of the line of therapy, were randomized to probiotic‐supplemented (two 4 oz. servings of the probiotic yogurt product daily) or probiotic‐restricted arms. Stool samples were collected prior to therapy and at weeks 2, 3, 4, and 12. Microbiome composition was assessed using whole‐metagenome sequencing. A total of 20 patients were randomized. Bifidobacterium animalis, the active ingredient of the probiotic supplement, reached detectable levels in all patients in the probiotic‐supplemented arm versus two patients in the probiotic‐restricted arm. Clinical benefit rate was similar in probiotic‐supplemented versus probiotic‐restricted arms (70% vs. 80%, p = 0.606). Linear discriminant analysis (LDA) effect size analysis of MetaPhIAn2 abundance data predicted 25 enriched species demonstrating an LDA score >3 in either clinical benefit or no clinical benefit. In patients with clinical benefit (vs. no clinical benefit), Barnesiella intestinihominis and Akkermansia muciniphila were significantly more abundant (p = 7.4 × 10−6 and p = 5.6 × 10−3, respectively). This is the first prospective randomized study demonstrating modulation of the gut microbiome with a probiotic in mRCC. Probiotic supplementation successfully increased the Bifidobacterium spp. levels. Analysis of longitudinal stool specimens identified an association between B. intestinihominis, A. muciniphila, and clinical benefit with therapy. Trial Registration: NCT02944617 [ABSTRACT FROM AUTHOR]

Background: Infigratinib (BGJ398) is a potent and selective fibroblast grown factor receptor 1 to 3 (FGFR1-3) inhibitor with significant activity in patients with advanced or metastatic urothelial carcinoma bearing FGFR3 alterations. Given the distinct biologic characteristics of upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB), the authors examined whether infigratinib had varying activity in these settings.Methods: Eligible patients had metastatic urothelial carcinoma with activating FGFR3 mutations and/or fusions. Comprehensive genomic profiling was performed on formalin-fixed, paraffin-embedded tissues. Blood was collected for cell-free DNA analysis using a 600-gene panel. Patients received infigratinib at a dose of 125 mg orally daily (3 weeks on/1 week off) until disease progression or intolerable toxicity occurred. The overall response rate (ORR; partial response [PR] plus complete response [CR]) and disease control rate (DCR; CR plus PR plus stable disease [SD]) were characterized.Results: A total of 67 patients were enrolled; the majority (70.1%) had received ≥2 prior antineoplastic therapies. In 8 patients with UTUC, 1 CR and 3 PRs were observed (ORR, 50%); the remaining patients achieved a best response of SD (DCR, 100%). In patients with UCB, 13 PRs were observed (ORR, 22%), and 22 patients had a best response of SD (DCR, 59.3%). Notable differences in genomic alterations between patients with UTUC and those with UCB included higher frequencies of FGFR3-TACC3 fusions (12.5% vs 6.8%) and FGFR3 R248C mutations (50% vs 11.9%), and a lower frequency of FGFR3 S249C mutations (37.5% vs 59.3%).Conclusions: Differences in the cumulative genomic profile were observed between patients with UTUC and those with UCB in the current FGFR3-restricted experience, underscoring the distinct biology of these diseases. These results support a planned phase 3 adjuvant study predominantly performed in this population. [ABSTRACT FROM AUTHOR]

Objective: Rare cancers are a heterogeneous group of conditions that can be associated with emotional and physical impairments. In view of the dearth of research in this area, we investigated the quality of life and prevalence of distress in a cohort of patients diagnosed with a rare cancer, classified by the RARECARE definition. Methods: A cohort of rare cancer patients, treated in a Brazilian public cancer center, was assessed for distress (Distress Thermometer), anxiety/depression (Hospital Anxiety and Depression Scale), and quality of life (Functional Assessment of Cancer Therapy‐General Version). Descriptive statistics were generated, and multivariate analyses were used to identify factors associated with distress, anxiety/depression, and quality of life. Results: A total of 137 patients (52.6% male, mean age of 50 years; range 18‐90) were identified. Nearly half (49.6%) of patients reported high levels of distress, with 19.7% endorsing anxiety and 15.3% depression. In multivariate analysis, demographic and clinical variables associated with worse psychosocial outcomes included younger age (P < 0.05), female gender (P < 0.01), advanced disease stage (P < 0.01), and engagement in active therapy (P < 0.05). Conclusions: Patients diagnosed with rare cancer reported poorer psychosocial outcomes and impaired quality of life when compared to the general population of cancer patients. Certain demographic groups (eg, women and younger patients) may benefit from targeted psychosocial interventions. [ABSTRACT FROM AUTHOR]