tbuckley/cabot-search huggingface dataset:
A randomized phase II trial of secondary cytoreductive surgery (SCS) +/- carboplatin hyperthermic intraperitoneal chemotherapy (HIPEC) in patients (pts) with recurrent platinum-sensitive ovarian cancer (EOC).
Authors: Oliver Zivanovic, Dennis Chi, Qin Zhou, Alexia Iasonos, Vicky Makker, Rachel N. Grisham, Jason A. Konner, John Paul Diaz, Amy K. Brown, Carrie L Langstraat, Viktoriya Paroder, Krysten Soldan, Katy Su, Ginger J. Gardner, Elizabeth Lin Jewell, Kara Long, William P. Tew, Stuart M. Lichtman, Yukio Sonoda, Roisin Eilish O'Cearbhaill
Journal: Journal of Clinical Oncology (2020)

6016 Background: The role of HIPEC for recurrent EOC is not well defined. The aim of this phase II study was to determine the proportion of pts without evidence of disease progression at 24 months post SCS +/- intraoperative carboplatin HIPEC. Methods: After SCS to ≤ 0.5 cm residual visible disease pts were intraoperatively randomized to carboplatin HIPEC (800mg/m 2 for 90 minutes) or no HIPEC. The HIPEC arm received 5 additional and the standard arm received 6 postoperative cycles of IV platinum-based chemotherapy without maintenance treatment. Based on an exact binomial single stage “pick the winner” design, each arm is considered “winner” if ≥ 17/49 pts are without evidence of disease progression at 24 months post SCS. Secondary objectives include postoperative grade ≥ 3 toxicity and complications within 4 weeks post SCS, and pharmacokinetics of carboplatin HIPEC. Results: Of 98 pts, 49 (50%) were randomized to the HIPEC arm. The arms were well balanced for age, stage, histology, BRCA mutation status, prior chemotherapy, and disease-free interval. Complete gross SCS was achieved in 94% of the standard and 82% of the HIPEC arm (p = 0.12). Bowel resection was performed more frequently in the standard (65%) compared to the HIPEC arm (37%; p = 0.008). Median operative time was shorter in the standard (296 minutes) compared to the HIPEC arm (475 minutes; p &lt; 0.001). There was no perioperative mortality and no difference in use of ostomies, length of stay or postoperative toxicity. At a median follow-up of 27.7 months (range: 8.8-81.8 months) 70 of 98 pts progressed and 26 died with a median progression free survival (PFS) of 14.3 months (12.1-16 months) and a median overall survival (OS) of 55.2 months (47.7-not reached). At 24 months post SCS 32 pts progressed within 24 months in the standard versus 35 in the HIPEC arm. There was no statistically significant difference in median PFS (15.4 vs 12.3 months, p = 0.173) or median OS (69.2 vs 53.1 months, p = 0.317) between arms. These are preliminary efficacy estimates as 83/98 pts have a minimum of 24 months follow-up. Conclusions: The HIPEC arm did not reach the predefined “winner” endpoint; the standard arm is still undetermined as 6 pts did not reach 24 months follow-up. No perioperative mortality, and no increased perioperative morbidity or toxicity was seen with HIPEC. SCS with carboplatin HIPEC followed by 5 cycles of platinum-based chemotherapy was not superior to SCS without HIPEC followed by 6 cycles of platinum-based chemotherapy. Clinical trial information: NCT01767675.
Examination of PD-1/PD-L1 inhibitor use and adverse events in a real-world setting.
Authors: Debra E. Irwin, Brenna L. Brady
Journal: Journal of Clinical Oncology (2020)

e19294 Background: Immune checkpoint blockade through PD-1 and PD-L1 inhibition is an effective treatment for multiple cancers. This study used administrative claims to examine potential adverse events (AEs) associated with real-world PD-1 or PD-L1 inhibitor use. Methods: Adult patients newly initiating a PD-1 (pembrolizumab or nivolumab) or PD-L1 (atezolizumab, avelumab, or durvalumab) inhibitor from September 1, 2016 to August 30, 2018 were selected in the MarketScan Commercial and Medicare Supplemental Database. Patients were grouped by use of PD-1 or PD-L1 inhibitor; the study period consisted of 90 days baseline and 60 days follow-up around drug initiation. Patients who used both PD-1 and PD-L1 inhibitors during follow-up were excluded. Clinical characteristics were examined during baseline, while AEs were investigated over follow-up. Results: A total of 6,430 patients qualified for the analysis. The majority of the sample (N = 5,956; 93%) received PD-1 inhibitors. Compared to the PD-1 cohort, the PD-L1 cohort was older (64±10 vs. 61±12 yrs) and more likely to be male (61% vs. 56%), p &lt; 0.05. PD-L1 patients were significantly more likely to have history of chronic pulmonary disease (28% vs. 23%) or myocardial infarction (4% vs. 3%) but less likely to have liver disease (2% vs. 0.6%) compared to PD-1 patients, p &lt; 0.05. Lung cancer was the most common diagnosis in both groups (PD-1: 47%; PD-L1: 62%, p &lt; 0.001). The PD-L1 cohort was more likely to have evidence of bladder cancer (36% vs. 5%), while the PD-1 cohort was more likely to have a melanoma (19% vs. 0.8%) or renal cell carcinoma diagnosis (10% vs. 7%), p &lt; 0.05. Over half of the PD-1 (65%) and PD-L1 (61%) patients had metastatic cancer diagnosis during the study period. Incident AEs occurring in &gt; 5% of the sample included dyspnea (PD-1: 13%; PD-L1: 14%), nausea/vomiting (PD-1: 11%; PD-L1: 8%, p &lt; 0.05), anemia (PD-1: 11%; PD-L1: 12%), fatigue (PD-1: 10%; PD-L1: 12%), abdominal pain (PD-1: 7%; PD-L1: 7%), cough (PD-1: 7%; PD-L1: 10%, p &lt; 0.05), back pain (PD-1: 7%; PD-L1: 10%, p &lt; 0.05), constipation (PD-1: 6%; PD-L1: 8%), arthralgia (PD-1: 6%; PD-L1: 6%), pyrexia (PD-1: 5%; PD-L1: 8%, p &lt; 0.01), and edema (PD-1: 6%; PD-L1: 5%). Conclusions: This study assessed real-world AEs associated with PD-1/PD-L1 inhibitor use in the 60 days following first treatment. Results showed AEs are common soon after starting therapy. Although, PD-1 and PD-L1 inhibitors target the same pathway, slightly different AE profiles exist for the two classes. More longitudinal analyses of real-world AEs are needed to better understand potential impacts of prolonged therapy.
Identification and in silico structural insights of rare recurrent <i>EGFR</i> mutations as resistance mechanisms to osimertinib in <i>EGFR</i>-mutated lung cancer.
Authors: N/a Zhoutong, Changling Wu, Binbin Lu, Ran Cao, Yutong Ma, Hua Bao, Qiuxiang Ou, Xue Wu, Yang Shao, Zhaoxia Wang
Journal: Journal of Clinical Oncology (2020)

9531 Background: Inevitable progression on 3 rd -generation EGFR-tyrosine kinase inhibitor (TKI) osimertinib of EGFR-mutated lung cancer patients represents a great challenge in clinic. Previous studies have revealed that one-third of the resistant mechanisms are due to acquired EGFR secondary mutations, mainly on C797, L718 and L792 residues. Our study aims to gain insights into novel mechanisms of acquired resistance to osimertinib. Methods: We performed genomic profiling on a total of 1,058 EGFR-mutated lung cancer patients with progressed disease on osimertinib, and a cohort of 1,803 patients who received only 1 st -generation EGFR TKIs upon progression. Recurrent EGFR mutations with a significant enrichment in the osimertinib group were identified. We further established and applied molecular dynamic simulation-based computational model of the mutant EGFR protein to predict its sensitivity to osimertinib. Results: As expected, compared with 1 st -TKIs alone group, EGFR mutations, including C797S/G (22.1% vs. 0.5%), L718Q/V (6.2% vs. 0.3%), L792F/H (4.4% vs. 0.3%), were significantly more enriched in the osimertinib cohort. Our computational model has also successfully predicted their sensitivities to osimertinib: WT (-35.19 kcal/mol) &gt; L792F (-34.10 kcal/mol) &gt; L718Q (-30.33kcal/mol) &gt; C797S (-28.02 kcal/mol), which are consistent with our previous in vitro validations. Importantly, a total of 14 low-frequency EGFR mutations were exclusively observed in the osimertinib group, seven of which, including EGFR G796S(n = 6), V802F(n = 3), T725M(n = 2), Q791L/H(n = 2), P794S/R(n = 2), were predicted to dramatically reduce the binding affinity of osimertinib to EGFR. Of note, analysis of the pretreatment samples of two patients supported that EGFR V802F and Q791L/H were acquired during osimertinib treatment. Interestingly, EGFR G796S was predicted to be sensitive to gefitinib, suggesting the possibility of administration of gefitinib in patients with acquired EGFR G796S to first-line osimertinib treatment. Further in vitro functional validations are currently ongoing. Conclusions: Our study represents the largest EGFR-mutated lung cancer cohort so far to investigate osimertinib resistance in a real-world setting, and has uncovered a list of recurrent low-frequency EGFR mutations that may confer acquired resistance to osimertinib. Our in silico structural model was proved to be powerful and robust in the prediction of osimertinib sensitivity of EGFR mutants.
Burden of relapsed/refractory (RR) acute myeloid leukemia.
Authors: Sumeet Panjabi, Dionne M. Hines, Catherine Balderston McGuiness, Emre Yucel, Steven Yea, Zachariah McIver, Rolin L Wade
Journal: Journal of Clinical Oncology (2020)

e19509 Background: To examine treatment patterns and health care costs of RRAML in the US. Methods: We identified adults with ≥ 2 outpatient or ≥ 1 inpatient claim with a diagnosis of AML from 1/1/2011 to 12/31/2017 (first AML claim = index date) using IQVIA’s fully-adjudicated Health Plan Claims Data. Continuous health plan enrolment for ≥ 12 months prior to the index date and ≥ 1-month post-index, a RRAML diagnosis on or prior to the index date, or with hematopoietic stem cell transplantation (HSCT) or chemotherapy pre-index were required. Patients were grouped by post-index treatment (high- or low-intensity chemotherapy [HIC, LIC] with and with no HSCT, HSCT only, best supportive care [BSC], or no treatment within 90 days of index [NoTx]). Costs were evaluated for 12 months following index. Results: The final sample of patients with RRAML (n = 804) were grouped by age:18-59 (n = 411; 51.2%), 60-74 (n = 318; 39.5%), and ≥75 years (n = 75; 9.3%). Treatment within the three age cohorts was: HIC (13%, 11%, 1%); LIC (27%, 38%, 52%); HIC+HSCT (14%, 7%, 0%); LIC+HSCT (2%, 3%, 0%); HSCT (9%, 9%, 0%); BSC (21%, 21%, 31%); NoTx (13%, 12%, 16%), respectively. Mean monthly costs were lowest for BSC and highest for HSCT or HIC containing treatments, irrespective of age (Table). Inpatient costs were 50 to 100% of total costs. Monthly costs across treatment/age groups were higher earlier in treatment [month 1 range: $28,627 (BSC) to $180,867 (HIC)] and declined over time [month 12 range: $2,853 (BSC) to $53,003 (HIC+HSCT)]. Conclusions: Nearly half of all patients age ≥75 years and 33% of patients &lt; 75 years received BSC or NoTx, which highlights a significant unmet need for new treatment options. Average costs per patient, especially early in treatment are high and driven by hospital service utilization. [Table: see text]
Poor performance status and front-line pembrolizumab in advanced non-small-cell lung cancer (NSCLC) patients with PD-L1&gt;50%.
Authors: Alfredo Addeo, Giulio Metro, Diego Signorelli, Panagiota Economopoulou, Fausto Roila, Giuseppe Luigi Banna, Alessandro De Toma, Andrea Camerini, Athina Christopoulou, Giuseppe Lo Russo, Domenico Galetta, Beatriz Jimenez Munarriz, Ana Collazo, Antonio Calles, Panagiotis Baxevanos, Helena Linardou, Paris A. Kosmidis, Giannis Socrates Mountzios, Marina Chiara Garassino, Alex Friedlaender
Journal: Journal of Clinical Oncology (2020)

e21651 Background: We retrospectively analysed real-world clinical outcomes of patients with advanced non-small-cell lung cancer (NSCLC) harbouring high PD-L1 expression ( &gt; 50%) and treated with first-line pembrolizumab, following the Keynote 024 regimen. In the recent PePS2 trial and Checkmate 817, we see that some patients with PS2 could benefit from a durable response to checkpoint inhibitors. However, current data does not suggest an improvement in median OS compared to historical data on chemotherapy in this setting. Methods: Data was collected by 16 participating centers. The trial was approved by local ethics committees and patients included signed a general consent form. All patients with NSCLC with PD-L1 expression ≥50%, treated with first-line pembrolizumab were included, from the introduction of first-line pembrolizumab to the present. We collected medical data from patient files, pathology reports and laboratory reports for all patients. Patient characteristics, comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and tumor characteristics were reported. Overall survival (OS) was calculated from the date of the first cycle of pembrolizumab to death and estimated through the Kaplan-Meier method. Results: 302 patients were identified, of which 247 with a PS of 0-1, 52 with a PS of 2. Patients (3) with PS3 were excluded. The median age was 69 with a range from 19 to 87 years. There were 193 males and 106 females, 90% were active or former smokers, 19% had brain lesions at diagnosis. Only 14% received brain radiotherapy. Median OS was 7.2 months among patients with PS2, while not reached for those with PS0-1 (HR 3.80, 95% confidence interval 2.49-5.78). Conclusions: Patients with a PS of 2 had significantly worse survival than those with PS0-1. The retrospective nature of our trial and lack of a control arm treated with chemotherapy do not allow us to postulate as to whether PS is predictive or prognostic. Our data suggests worse survival among NSCLC patients with PS2 treated with front-line pembrolizumab. A prospective randomized trial comparing immunotherapy to chemotherapy or chemo-immunotherapy in this population would be welcome.
糖尿病并痛性眼肌麻痹一例
Authors: 吴金枝
Journal: BMJ (2006)

患者男,53岁,因多饮、多尿、多食、消瘦1个月,头痛伴左眼睑下垂3 d于2005年9月21日人院.入院前10 d有上呼吸道感染病史.查体:血压106/68 mm Hg(1 mm Hg=0.133 kPa),神志清楚,口角无歪斜,左眼睑下垂,左眼外斜15°,内转受限,视力正常,右眼球活动无异常,双侧瞳孔等圆、等大,对光反应正常.外周血常规:白细胞11.2×109/L,中性粒细胞0.58;头颅磁共振成像检查未见异常;空腹血糖13.9 mmolL,餐后2 h血糖18.9 mmolL,吡啶新斯的明试验阴性,初步诊断为糖尿病性动眼神经麻痹,予控制血糖、营养神经、改善循环、止痛等治疗10 d,血糖控制好,但头痛无缓解,左眼睑仍下垂,予甲基强的松龙80 mg/d静脉滴注、共10 d,并补充B族维生素,头痛缓解,左眼睑活动正常。
Impact of sarcopenia on muscle strength and exercise capacity in elderly patients with chronic heart failure
Authors: Xiao Xiao, Song Hu, Ting Zhao, Jia Liu, Nina An, Yongjun Mao
Journal: BMJ (2019)

Objective
To investigate the impact of sarcopenia on muscle strength and exercise capacity in elderly patients with chronic heart failure (CHF).


Methods
One hundred and sixteen inpatient aged ≥65 years with CHF were enrolled in the study. General clinical characteristics were collected with questionnaire; the appendicular skeletal muscle mass (ASM) was assessed with body composition analyzer; the arm muscle strength was measured and a 6m-walk test was performed. The sarcopenia was evaluated according to the Asian Working Group for Sarcopenia (AWGS) criteria. Simple regression analysis and logistic regression were used to analyze the correlation between sarcopenia and decreased muscle strength, exercise capacity in elderly CHF patients.


Results
Among 116 elderly CHF patients, sarcopenia was confirmed in 42 patients(36.2%). Patients with sarcopenia had poorer cardiac function and lower muscle strength, ASM and 6m-walking speed than patients without sarcopenia did(allP<0.05). Simple regression analysis showed positive correlation between ASM and muscle strength in both groups. Logistic regression analysis showed that after adjustment for confounders, ASM reduction was an independent risk factor for reducedexercisecapacity(OR=0.158, 95%CI: 0.055-0.455, P<0.05).


Conclusion
Sarcopenia is a common complication in elderly patients with CHF and may lead to decreased muscle strength and exercise capacity.


Key words: 
Aged; Chronic heart failure; Sarcopenia; Exercise capacity
Outcomes and Immunogenicity of pancreatic cancer stratified by the HRDetect score.
Authors: Grainne M. O'Kane, Gun Ho Jang, Rob Denroche, Amy Zhang, Sarah Louise Picardo, Robert C Grant, Michael Allen, Yifan Wang, Anna Dodd, Stephanie Ramotar, Shawn Hutchinson, Mustapha Tehfe, James Joseph Biagi, Bernard Lam, Julie Wilson, Faiyaz Notta, Sandra Fischer, George Zogopoulos, Steven Gallinger, Jennifer J. Knox
Journal: Journal of Clinical Oncology (2020)

4630 Background: The HRDetect score uses whole genome sequencing (WGS) to incorporate patterns of substitution base signatures and structural variation to identify tumours deficient in homologous recombination repair (HRD). HRD-tumours, with a higher mutational burden, may be more immunogenic. Methods: We applied HRDetect to 182 resected pancreatic cancers (PDA) and 233 advanced PDA enrolled on the COMPASS trial; both cohorts underwent WGS after tumour enrichment. Patients were classified as high( hi ) or low( lo ) according to the published score threshold of 0.7; clinical characteristics and survival outcomes were determined. Immunogenicity of the cohorts was explored by analyzing cytolytic activity (CYT) as measured by RNA expression of perforin and granzyme A. Results: 14% of resected (25/182) and 14% of advanced cases (32/233) were considered HRDetect hi . The median age at PDA diagnosis was younger in HRDetect hi vs HRDetect lo (61 vs 66 years, p = 0.005), with no difference in sex between groups. Of the 57 cases identified, 37 (65%) were considered true HRD-PDA with inactivation of BRCA1, BRCA2, PALB2, RAD51C and XRCC2. The remaining 20 cases, were considered false positives for HRD; of these 7 had evidence of a tandem duplicator phenotype with duplications ranging from 10Kbp to 1Mbp in size and 13 had no defining genomic characteristics of the HRD-subtype. In resected PDA, the HRDetect score after adjusting for stage, was not prognostic. In contrast in a multivariable analysis of advanced cases, both HRDetect (HR 0.51, 95% CI 0.30-0.87, p = 0.01) and the Moffitt RNA classifier were highly prognostic (HR 1.99, 95% CI 1.32-3.00, p = 0.0001) with improved survival in HRDetect hi and classical PDA. Of patients receiving platinum in advanced disease (n = 128) HRDetect hi PDA had longer survival compared to the HRDetect lo (15.6 vs. 9.9 months, p = 0.02) although the interaction term between chemotherapy regimen (gemcitabine vs. platinum) and HRDetect score was not significant in this cohort. HRDetect hi tumours had increased cytolytic activity than HRDetect lo PDA; furthermore, within the cohort of HRDetect hi PDA, higher CYT scores were evident in primary lesions compared to metastatic sites sequenced. Conclusions: A high HRDetect score is prognostic in advanced PDA where patients treated with platinum have longest survival. HRDetect hi tumours have increased cytolytic activity with differences observed between primary and metastatic lesions.
针刺联合挹神汤治疗失眠36例
Authors: 刘春生
Journal: BMJ (2010)

挹神汤是焦树德[1]治疗神经衰弱、癔病、更年期综合征、狂躁症、忧郁症等病的经验方,对中医辨证屑肝肾阴虚、肝阳偏旺者有较好的疗效,笔者对36例依赖口服艾司唑仑的失眠患者,用挹神汤加减配合针刺进行替代治疗,效果如下. 一、研究对象 1.研究对象:入选36例患者均为2008年1月至2010年3月在本站就诊、求助于中医治疗失眠者,符合 [2]中失眠症的诊断标准,且匹兹堡睡眠质量指数(PSQI)[3]7个因子成分的累积分＞7,中医辨证以肝阳亢旺、阴血亏虚为主,主症为难以入睡、睡眠不深、易醒、多梦、早醒、醒后不易再睡、醒后不适、头晕头疼、急躁易怒或精神不振、脘腹胀满、纳谷不香、大便溏泄.持续1个月以上。
Microbiome and host crosstalk: A new paradigm to cancer therapy
Authors: Ashutosh Singh, Namyashree Nayak, Preeti Rathi, Deepanshu Verma, Rohit Sharma, Ashun Chaudhary, Alka Agarwal, Yamini Bhushan Tripathi, Neha Garg
Journal: Seminars in Cancer Biology (2020)
心律失常性右心室心肌病一例分析
Authors: 王春玲, 石宁, 邹阳春, 王明晓
Journal: BMJ (2010)

心律失常性右心室心肌病(ARVC)或称心律失常性右心室发育不良,主要由编码细胞桥粒蛋白的基因突变引起,导致细胞间交通障碍,进行性心肌细胞缺失和纤维脂肪组织取代右心室心肌细胞[1],以频繁发作的室性心动过速、心力衰竭和猝死为特征.美国心脏学会(AHA)和我国中华医学会分别于1996年及1999年正式将致心律失常性右室心肌病列为第四类原发性心肌病,与扩张型心肌病等并列.该类疾患的心电图有其独特表现.我们临床随访1例致心律失常性右室心肌病患者,将其心电图特点及相关基因检测结果结合国内外文献分析报道如下。
Cabazitaxel versus enzalutamide/abiraterone in CARD eligible mCRPC patients with or without germline HRR defects.
Authors: Nuria Romero-Laorden, Rebeca Lozano, Casilda Llacer Perez, Jose Maria M. Piulats Rodriguez, Javier Puente, David Lorente, Ana Medina, Carlo Cattrini, Francesca Vitrone, Elena Almagro, Pablo Borrega, Nuria Lainez, Leticia Rivera, Rosa Villatoro, Amaia Hernandez, Alejo Rodriguez-Vida, Pedro P. López-Casas, Enrique Gallardo Diaz, Elena Castro, David Olmos
Journal: Journal of Clinical Oncology (2020)

5554 Background: The CARD trial proved that in mCPRC patients (pts), previously treated with docetaxel and an androgen-receptor signaling inhibitor (ARSi), cabazitaxel (CBZ) significantly improves progression-free (PFS) and Overall Survival (OS) compared with the alternative ARSi. Concurrently, the PROFOUND study showed the superiority of olaparib vs. ARSi in pts with similar prior treatment history and genetic alterations in Homologus Recombination DNA repair related genes (HRR). Methods: PROREPAIR-B (NCT03075735) is a prospective study which aimed to demonstrate the prognostic role of germline deleterious mutations in (g)HRR genes and the benefit of first (1L), second (2L) and subsequent therapy lines for mCRPC. Outcomes with 1-2L have been previously reported. Here we evaluated radiographic (r)-PFS, clinical (c)-PFS, and OS in PROREPAIR-B pts who meet CARD study eligibility criteria and who received CBZ and/or ARSi. Survival analysis were performed using Kaplan Meier method and Cox regression models. Results: 95 out of 419 mCRPC pts included in PROREPAIR-B meet CARD eligibility criteria and received CBZ (n=60) or ARSi (n=35) including 14 gHRR carriers, 8/6 treated with CBZ/ARSi, respectively. Visceral metastases were more frequent among pts treated with CBZ (p=0.01). ECOG 2, M1 at diagnosis, Abiraterone as 1 st ARSi and prior radiographic PD (all p&lt;0.05) were more frequent in our pts than in the CARD study. Overall, CBZ was superior to ARSi in terms of rPFS (median 6.0 vs. 3.7 months (m), p=0.03), cPFS (median 4.4 vs. 3.4 m, p=0.01) and PSA50 responses (39% vs. 17%, p=0.027). Differences in OS were not observed, although approximately 60% of patients in ARSi had crossed to CBZ at the time of the analyses. Results of subgroups analyses were similar to those reported by CARD. In this series, gHRR carriers had a significant worse prognosis (OS HR 1.9; rPFS HR 2.4; cPFS HR 2.6) than non-carriers. In gHRR carriers CBZ was not superior to ARSi in terms of rPFS (2.5 vs. 3.0 m, p=0.8), cPFS (2.5 vs. 2.4 m, p=0.8) and OS (4.5 vs. 3.7, p=0.8). Cox MVA models adjusted for unbalances and CARD grouping factors confirmed a significant interaction between treatment and gHRR status for rPFS and cPFS, suggesting that the benefit of CBZ was not observed in gHRR. Conclusions: Our results confirm the benefit of CBZ treatment over a second ARSi (either abiraterone or enzalutamide) in unselected mCRPC population. However, the outcomes in gHRR carriers are poor with either CBZ or ARSi supporting the need of novel therapies in this setting. Clinical trial information: NCT03075735 .