bluuebunny/crossref_metadata_2025_split huggingface dataset:
Camrelizumab plus apatinib for previously treated advanced adrenocortical carcinoma: A single-arm, open-label, phase 2 trial.
Authors: Wei Zhigong , Zhu Yuchun , Cai Lei , Peng Xingchen 
Published: June 2024

4511 Background: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with dismal prognosis. Therapeutic options for patients with advanced ACC after failure of standard treatments are limited. The clinical benefit of single-agent immunotherapy as second-line therapy was still unsatisfactory. Methods: This was an investigator-initiated, prospective, single-arm, open-label, phase 2 trial and conducted at a single medical center. Patients were eligible for inclusion if they were aged at least 18 years; were pathologically diagnosed as unresectable or metastatic ACC; had failed first-line therapy; had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; had at least one measurable lesion; and had adequate organ function. The key exclusion criteria included a history of treatment with immunotherapy, anti-angiogenic small molecule TKIs, or anti-angiogenic monoclonal antibodies; a history of uncontrolled hypertension; and a history of an autoimmune condition requiring systemic therapy. All study participants received camrelizumab 200 mg intravenously on the first day of each 3 week cycle, combined with apatinib 250 mg orally once per day until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was objective response rate (ORR), defined as the proportion of participants with complete response (CR) or partial response (PR) per RECIST (version 1.1). Results: A total of 21 patients with advanced ACC received at least one dose of camrelizumab and apatinib. ORR was 52% (95% CI, 30 to 74), and the disease control rate was 95% (95% CI, 84 to 100), superior to PD-1 inhibitor monotherapy and first-line standard therapy. The median PFS was 12.6 months (95% CI, 8.4 to 20.9), and the median OS was 20.9 months (95% CI, 11.0 to 20.9). The most common grade 3—4 treatment-related adverse events were alanine aminotransferase elevation (28.6%), aspartate aminotransferase elevation (23.8%) and lymphopenia (23.8%). Our exploratory analysis showed higher peripheral blood CXCR3+CD8+ T cell abundance, lower immunosuppressive CD4+ T cell abundance, and higher overlap of clonotypes between tumor-infiltrating T cells and circulating T cells, likely related to preferable response to camrelizumab plus apatinib therapy. Conclusions: In conclusion, the combination of camrelizumab with apatinib showed promising activity and acceptable toxicity in advanced ACC patients who failed previous lines of therapy. Pre-treatment peripheral blood immune cell subsets could be regarded as potential predictors of efficacy. Given the promising clinical activity, the potential of camrelizumab with apatinib as first-line therapy for advanced ACC need further evaluated. Clinical trial information: NCT04318730 .
Health-related quality of life and pain in a phase 3 study of [177Lu]Lu-PSMA-617 in taxane-naïve patients with metastatic castration-resistant prostate cancer (PSMAfore).
Authors: Fizazi Karim , Morris Michael J. , Shore Neal D. , Chi Kim N. , Crosby Michael , De Bono Johann S. , Herrmann Ken , Roubaud Guilhem , Nagarajah James , Fleming Mark T. , Lewis Brian E. , Nordquist Luke , Castellano Daniel , Carnahan Natalie , Ghebremariam Samson , Hertelendi Marianna , Sartor Oliver 
Published: June 2024

5003 Background: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolonged radiographic progression-free survival vs change of androgen receptor pathway inhibitor (ARPI) in taxane-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) in PSMAfore (NCT04689828). We now present health-related quality of life (HRQoL) and pain outcomes at second interim analysis. Methods: Eligible patients had mCRPC, were candidates for change of ARPI after progression on one prior ARPI, and had ≥1 PSMA-positive and no exclusionary PSMA-negative metastatic lesions by [68Ga]Ga-PSMA-11 PET/CT. Ineligible patients were candidates for PARP inhibition or had received prior systemic radiotherapy, immunotherapy or chemotherapy. Patients were randomized 1:1 to open-label 177Lu-PSMA-617 (7.4 GBq/6 weeks; 6 cycles) or ARPI change (abiraterone/enzalutamide). Patients with confirmed radiographic progression on ARPI change could cross over to 177Lu-PSMA-617. Secondary endpoints included time to worsening (TTW) in self-reported HRQoL (FACT-P, EQ-5D-5L) and pain (BPI-SF), defined as a composite of score worsening (prespecified thresholds), clinical progression (including new anti-cancer treatment) or death. Post hoc analyses of TTW in FACT-P and BPI-SF excluded clinical progression and death. The study was not powered for these endpoints and type I error was not controlled. Results: We randomized 468 patients (234/arm) with a median age of 72 years (range, 43–94). Median duration of exposure was 8.4 months for 177Lu-PSMA-617 and 6.5 months for ARPI change. 177Lu-PSMA-617 delayed TTW in FACT-P, EQ-5D-5L and BPI-SF scales and subscales vs ARPI change (Table). Results were similar in non-composite analyses. Incidence of grade ≥3 adverse events (AEs), serious AEs and AEs leading to discontinuation for 177Lu-PSMA-617 and ARPI change were 34% vs 44%, 20% vs 28% and 5.7% vs 5.2%, respectively. Conclusions: 177Lu-PSMA-617 delayed TTW in self-reported pain and HRQoL vs change of ARPI in taxane-naïve patients with PSMA-positive mCRPC. Clinical trial information: NCT04689828 . [Table: see text]
Prevalence of HER3 expression in prostate adenocarcinoma and its clinicopathological characteristics.
Authors: Rajendran Rithika , Lap Coen Johannes Gerardus , Estephan Fayez , Liu Shanshan , Subrahmanyam Ramesh , Diao Guoqing , Nava Victor , Jain Maneesh Rajiv 
Published: June 2024

5019 Background: Human epidermal growth factor receptor 3 (HER3) has been found upregulated in a wide variety of cancers and has been associated with disease progression and resistance to EGFR-targeted therapies in HER2-positive malignancies. Several studies have reported expression of HER3 in prostate cancer (PCa). Furthermore, concurrent expression of HER2 and HER3 in PCa has been associated with androgen resistance, development of metastatic disease, and less favorable outcomes. However, due to conflicting results, the exact nature of the relationship between HER2 and HER3 in PCa requires further investigation. Methods: 194 patients diagnosed with PCa between 2000-2021 at the Washington DC Veterans Affairs Medical Center who had adequate formalin-fixed paraffin embedded prostate tissue available were selected from our previously published cohort of patients. HER3 immunostaining was performed and independently scored by two pathologists as 0 (absent), 1+ (weak), 2+ (moderate), or 3+ (marked). HER2 immunostaining data and clinical information was retrieved. Statistical analysis included Fisher’s exact test and linear regression models. Results: In our self-identified predominantly African American (85%) patient cohort, a 94% overall prevalence of HER3 positivity (1+, 2+, or 3+) was observed. Notably, the majority of positive patients was found to have HER3 expression of either 2+ (~60%; 116/194) or 3+ (~17%; 33/194). HER3 positivity was associated with a higher PSA ( p=0.023), a higher Grade Group (GG) ( p=0.017), and a higher AJCC disease stage ( p=0.006) at time of diagnosis (Table 1). A significant association was observed between positivity for both HER2 and HER3 ( p=0.031). HER3 positivity independently predicted GG ( p=0.02) and AJCC disease stage ( p=0.01) when adjusted for HER2 positivity. Conclusions: In this predominantly African American cohort, a high prevalence of HER3 positivity was observed across PCa disease stages. Higher expression levels of HER3 were observed in more advanced stages of the disease. Because of the observed efficacy of HER3-antibody drug conjugates in other HER3-expressing malignancies, the high prevalence of HER3 in PCa makes it an attractive therapeutic target that warrants further evaluation.[Table: see text]
Real-world evidence of overall survival (OS) and treatment patterns of patients (pts) with testicular germ cell tumors (GCT) receiving palliative chemotherapy in the United States.
Authors: Feldman Darren R. , Habucky Karen , Gagnon-Sanschagrin Patrick , Maitland Jessica , Boileau Philippe , Yokoji Kana , Guérin Annie , Joseph George 
Published: June 2024

5038 Background: Pts with relapsed/refractory (R/R) GCT have a poor prognosis, with only palliative options remaining. Real-world data in this population, particularly around prior salvage strategies with high-dose (HDCT) or conventional-dose chemotherapy (CDCT), are needed to inform future treatment standards. Methods: Adult males with R/R testicular GCT who received palliative chemotherapy between 01/2016 to 03/2023 were identified in the Komodo Research Database Demographics were described on the index date, defined as the date of palliative chemotherapy initiation. OS, defined as the time from index date to death and stratified by prior HDCT exposure, was assessed among pts with 12 months (mos) follow-up time using the Kaplan-Meier method. Additionally, treatment patterns were analyzed in a subgroup of pts with an eligible health plan continuously from diagnosis to index date. Results: Of 57,508 pts with testicular GCT, 248 received palliative chemotherapy, among whom 97 (39.1%) had sufficient claims data to confirm prior exposure to salvage HDCT (+/- CDCT) or only CDCT (57 HDCT; 40 CDCT only). Median (interquartile range [IQR]) age on the index date for these 97 pts was 32 (25-42) years and most had commercial (47.4%) or Medicaid (36.1%) insurance. Observed index palliative regimens included gemcitabine + oxaliplatin (46.4%), oral etoposide (12.4%), and gemcitabine + paclitaxel (12.4%); 24.7% of pts received multiple palliative regimens (median 2, range 2-5). Median (95% confidence interval) OS was 8.0 (6.3-9.7) mos; 7.0 (5.7-9.7) mos for those HDCT exposed, and 9.3 (7.5-22.6) mos for those exposed to CDCT only. The treatment patterns subgroup comprised 51 pts observed for a median of 19.9 (IQR: 15.6-28.8) mos after diagnosis. Median (IQR) time from diagnosis to first-line (1L) chemotherapy was 0.9 (0.5-2.1) mos and to palliative chemotherapy was 12.5 (9.0-16.8) mos. Prior to palliative chemotherapy, 33 pts (64.7%) received salvage chemotherapy, including HDCT (+/- CDCT) in 23 pts (69.7%) and only CDCT in 10 pts (30.3%). Of 18 pts (35.3%) who did not receive salvage chemotherapy prior to palliative chemotherapy, median time from end of 1L chemotherapy to index date was 4.1 (IQR: 2.4-8.0) mos and 13 pts (72.2%) had renal insufficiency. Conclusions: Real-world data was able to capture treatment patterns, palliative chemotherapy use, and outcomes for pts with R/R testicular GCT. Surprisingly, more than 1/3 of pts did not receive a salvage chemotherapy regimen prior to palliative chemotherapy and of those who did, >30% did not receive HDCT. Renal insufficiency may be a major reason for lack of salvage chemotherapy use. These data provide prognostic information and variables influencing poor outcome in this understudied population for whom novel treatments are urgently needed.
Race and association between ADT and adverse events.
Authors: Friedrich Nadine , Janes Jessica L. , Parrish Joshua , De Hoedt Amanda Marie , Tatonetti Nicholas , Freedland Stephen J. 
Published: June 2024

5073 Background: Many prior studies have linked androgen deprivation therapy (ADT) for prostate cancer (PC) with adverse events such as cardiac events and osteoporosis. Whether these associations differ by race is unknown. Methods: We performed a retrospective population-level analysis to assess the association between ADT (specifically GnRH agonist) use and time to cardiovascular events, bone fracture, new osteoporosis diagnosis, or time to composite event (i.e., the first of any of cardiovascular, bone fracture, or osteoporosis events) in the Veterans Affairs Health Care System (VA) as a function of race. We identified 790,916 patients from 2001-2021 who were diagnosed with PC and treated with ADT or no ADT. Given small numbers, patients treated with other forms of ADT including bilateral orchiectomy or GnRH antagonists were excluded. Patients were also excluded if they were missing race/ethnicity. Data were stratified by race/ethnicity including: Non-Hispanic White (White) 598,574, Non-Hispanic Black (Black) 145,267, Hispanic 30,139 and Other 16,936. Univariable and multivariable Cox proportional hazards models were used to test the association between ADT as a time-dependent covariate and time to the given event across all patients and as a function of race. Results: On multivariable analysis among all patients, ADT was associated with increased risk of cardiovascular events (HR 1.16, 95% CI 1.15- 1.17, p<0.001), bone fractures (HR 1.59, 95% CI 1.55-1.62, p<0.001), osteoporosis (HR 2.73, 95% CI 2.65-2.80, p<0.001), and composite event (HR 1.29, 95% CI 1.27-1.30, p <0.001). When stratified by race, ADT remained significantly associated with all outcomes in all races (all p<0.001). Compared to White men, among Black men, the HRs for ADT were slightly lower for cardiovascular events (1.09 vs. 1.18), bone fracture (1.35 vs 1.65), and composite event (1.19 vs 1.31), but slightly higher for osteoporosis (3.16 vs 2.64). HRs in Hispanics and Other races were very similar to those in White men. Conclusions: Consistent with many prior studies, we found that ADT was associated with increased risk of cardiovascular events and bone complications. Though risks differed slightly among Black men, overall differences were small. These findings demonstrate that ADT is associated with adverse cardiovascular and bone complications regardless of race. Better means to reduce ADT-associated risks are needed across all races.
Hematologic toxicity in 177lu-PSMA-617 treatment for mCRPC: Unraveling the impact of PSMA PET bone tumor volume (PSMA-bTTV).
Authors: Ghodsi Alireza , Demirci Ridvan Arda , Gulati Roman , Raychaudhuri Ruben , Cheng Heather H. , Hawley Jessica E. , Yezefski Todd , Haffner Michael C. , Montgomery Robert Bruce , Nelson Peter , Schweizer Michael Thomas , Yu Evan Y. , Chen Delphine L. , Iravani Amir 
Published: June 2024

5075 Background: Lutetium-177 prostate-specific membrane antigen (177Lu-PSMA-617) is a life-prolonging treatment approved by the FDA in metastatic castration-resistant prostate cancer (mCRPC), at a very late stage when there frequently reduced bone marrow reserve. We aim to report the incidence of hematologic toxicity during treatment and potential risk factors in a single-center study. Methods: This retrospective single-institution case series included mCRPC patients who underwent at least one cycle of 177Lu-PSMA-617 treatment between June 2022 and January 2024. Hematological parameters were documented at baseline, 3 weeks after each treatment, and before each subsequent treatment administration. Then, we captured the nadir values for each parameter during treatment. Hematologic toxicities were assessed using the Common Terminology Criteria for Adverse Events v5.0, with Grades 3 and 4 considered significant. Multivariable logistic regression analyses were conducted to investigate the association between hematological adverse events and baseline characteristics including PSMA-bTTV, measured by semi-automatic contouring of the PSMA-expressing whole-body bone metastases on pre-treatment PSMA PET. Results: Our study included 138 mCRPC patients (median age: 73y, prior chemotherapy: 92%, prior radiation: 43.5%, bone involvement: 89.1%), who underwent a median of 3 cycles (IQR: 2-5) of 177Lu-PSMA-617 treatment. At baseline, 8 (5.8%) patients had grade 3 anemia, 2 (1.4%) patients had grade 3 leukopenia, and 1 (0.7%) patient had grade 3 thrombocytopenia. Nadir values during treatment indicated that 23 (16.7%) had grade 3 anemia, 5 (3.6%) had grade 3 leukopenia, and 11 (8%) had grade 3 and 4 thrombocytopenia. Multivariable analysis of predisposing factors for hematologic adverse events showed that the PSMA-bTTV was significantly associated with occurrence of any grade ≥3 hematologic toxicity, anemia, and thrombocytopenia after adjusting for other baseline clinical variables (Table). Conclusions: Over 1 in 5 patients with mCRPC experienced significant hematologic adverse events during treatment with 177Lu-PSMA-617. Bone tumor volume is a possible risk factor for developing significant hematologic toxicity. [Table: see text]
Resources to address challenges in first-line treatment intensification in metastatic castration-sensitive prostate cancer (mCSPC): A discrete choice experiment.
Authors: Loeb Stacy , Agarwal Neeraj , El-Chaar Nader N. , de Ruiter Laura , Kim Janet , Mack Jessica , Bland Christopher S , Rich-Zendel Sarah , Sheldon Jay , Joo Jin Su , Dyson Judith 
Published: June 2024

5087 Background: Althoughfirst-line treatment intensification (TI) (i.e., androgen-deprivation therapy with chemotherapy, novel hormonal therapies, or both) is recommended in mCSPC guidelines, it is used in <1/3 of patients. Phase 1 of the IMPLEMENT study used an implementation science approach to identify barriers to and facilitators of TI. Phase 2 of IMPLEMENT aimed to prioritize these factors and identify resources to increase TI. Methods: A discrete choice experiment was developed for 300 US-based physicians (150 oncologists, 150 urologists) who manage mCSPC. It included 6 descriptions of potential resources to help with TI decisions, based on results from Phase 1. Respondents selected from pairs of resource sets the set they perceived as most helpful across 12 scenarios. We analyzed responses using a mixed-effects logistic regression model and calculated a coefficient of helpfulness for each resource to identify those with the strongest impact on physicians’ decisions. Coefficients were required to have a minimum value of zero, as resources would be optional. Results: Overall, physicians preferred decision support tools and databases of post-treatment options. Urologists found decision support tools most beneficial (coefficient of helpfulness 3.27; 95% CI 2.90-3.64), while oncologists preferred post-treatment databases (2.58; 95% CI 2.29-2.89) and clinical trial summaries (2.41; 95% CI 2.13-2.69). Tools to reduce administrative burden and information on outcomes of earlier vs later TI were not considered as helpful compared to other resources and across specialties. Conclusions: There were key differences between specialties in the helpfulness of resources, indicating substantial variability in clinical practice needs. These findings provide a clear path to develop concrete, specialty-tailored tools to increase guideline-concordant treatment of mCSPC. [Table: see text]
Impact of pre-treatment MRI capsular involvement and extraprostatic extension on metastasis free and overall survival in localized prostate cancer.
Authors: Kumar Abhishek , LaBella Dominic , Snider Michael , Acklin-Wehnert Scarlett , Gupta Rajan T. , Salama Joseph Kamel , Boyer Matthew J 
Published: June 2024

5097 Background: Multiparametric magnetic resonance imaging (mpMRI) is not currently included in prostate cancer (PC) staging. The purpose of this study was to test the association between mpMRI detected prostate capsule involvement and extraprostatic extension (EPE) with metastasis free survival (MFS) and overall survival (OS) in patients treated for localized PC. Methods: Patients treated for localized PC between 2000-2021 from the Veterans Affairs Prostate Data Core having an mpMRI prior to definitive treatment were identified. MRI reports were assessed for minor or significant capsule abutment (defined as greater than or equal to 1.5 cm of capsule contact or radiologist’s mention of long segment abutment), extracapsular extension (ECE), seminal vesicle invasion (SVI), or adjacent organ invasion (OI). mpMRI findings' impact on MFS by multivariable Fine-Gray competing-risks regression and OS by Cox regression were assessed. Results: Overall, 2,933 patients were included. Most pre-treatment mpMRIs (85%) occurred after 2016. 1,238 (42%) patients were Black. 569 (19%) patients had palpable disease. Median follow-up was 5 years. The 5-year cumulative incidence of metastasis was 10% (95% confidence interval (CI) 9-11%) and death was 7% (95% CI 6-9%). There were 643 (22%) patients with minor capsule abutment, 212 (7%) with significant capsule abutment, 281 (10%) with ECE, 103 (4%) with SVI, and 25 (1%) with OI. After controlling for age, race, prostate specific antigen level, grade group, clinical tumor stage, and treatment, the presence of significant capsule abutment, ECE, SVI, and OI were independently associated with MFS, but minor capsule abutment was not. On multivariable analysis controlling for the same factors, EPE (ECE, SVI, or OI) was associated with worse OS. Conclusions: In a modern, real-world cohort of localized PC patients from the largest integrated health system in the United States, significant capsule abutment and EPE on mpMRI are independently prognostic of MFS, but minor capsular abutment is not. EPE is associated with inferior OS. Given its independent prognostic value for MFS and association with OS, mpMRI should be more widely available to PC patients. Studies are ongoing to define its role as a standard staging tool. [Table: see text]