tbuckley/cabot-search huggingface dataset:
Thromboembolism (TE) in patients (pts) with bladder cancer treated with checkpoint inhibitors (CPIs).
Authors: Iris Yeong- Fung Sheng, Shilpa Gupta, Chandana A. Reddy, Dana E Angelini, Pauline Funchain, Tamara A. Sussman, Joseph Sleiman, Timothy D. Gilligan, Moshe Chaim Ornstein, Alok A. Khorana
Journal: Journal of Clinical Oncology (2020)

5042 Background: Most pts with bladder cancer will be treated with immunotherapy. There is concern for increased TE risk with CPIs in this already high risk population. We present the first analysis of the incidence and outcomes of venous (VTE) and arterial (ATE) thromboembolism in pts with bladder cancer treated with CPIs. Methods: Consecutive pts with bladder cancer treated with CPIs at the Cleveland Clinic from 1/2015 to 12/2019 were identified and TE events noted. Overall survival (OS) was estimated using Kaplan-Meier method and the impact of VTE on OS was evaluated using Cox proportional hazards regression. Results: Of 274 pts, 72% were men (median age 73.3 years, 89% white), 82% had pure UC, 92% had lower tract disease, and 67% had a Bajorin score ≥1 (median KPS 90, 61% visceral metastases), 59% had prior systemic therapy (median 1, range 0-4) and 36% had prior TE (14% ATE, 19% VTE, 0.4% both). At CPI initiation, 24% were on antiplatelet therapy, and 15% on therapeutic anticoagulation. CPI (median doses 5, range 8.5-59) included: 40% atezolizumab, 3% nivolumab, 57% pembrolizumab. VTE occurred in 14% (n = 37), including 8% DVT, 4% PE, 2% both. DVT locations were 56% lower limb, 26% upper limb, 15% visceral vein, 4% visceral+upper limb. 2% (n = 5) had ATE (1% CVA, 0.4% visceral, 0.4% left subclavian). 92% of VTE and all ATE occurred within 6 months of CPI initiation. The incidence of TE was 10.9% (95%CI 6.6%—15.1%) at 6 months and 19.8% (95%CI 13.3%-26.4%) at 12 months. 82% of VTE (mean 6 days) and all ATE (mean 5 days) resulted in hospitalization. Multivariate analysis showed TE (HR 2.296, 95%CI 1.451-3.632, p = 0.0004), Bajorin score 1 (HR 1.490, 95%CI 1.036-2.142, p = 0.0315), and Bajorin score 2 (HR 3.50, 95%CI 2.14-5.74, p &lt; 0.0001) were independently associated with worse OS. Conclusions: CPIs in bladder cancer pts are associated with a high TE risk, especially within six months of initiation. TE is associated with worsened survival. Further investigation into the risk factors for CPI-associated TE is needed to identify if benefits exist from thromboprophylaxis.
Patient-reported diarrhea impact on physical functioning and quality of life in clinical trial data submitted to the U.S. Food and Drug Administration.
Authors: Ting-Yu Chen, Bellinda King-Kallimanis, Lyna Merzoug, Mallorie Fiero, Jennifer J Gao, Julia A. Beaver, Vishal Bhatnagar, Paul Gustav Kluetz
Journal: Journal of Clinical Oncology (2020)

e19105 Background: Patient-reported outcomes can provide symptom and function data that complement standard oncology endpoints. Frequently, trials will conclude there was no clinically meaningful detriment to health-related quality of life (HRQL) or function, even when notable toxicity is observed. It is possible that mean change from baseline analyses obscures meaningful change in subgroups experiencing symptomatic toxicity. In this study, we explore how patients’ response to a diarrhea item related to physical function (PF) and HRQL in trials submitted to US FDA. Methods: We analyzed 3 randomized, double-blind breast cancer trials (early to late line metastatic) where diarrhea was a more common AE-symptom in the treatment arm, but there was not a large detriment in the mean change from baseline for HRQL and PF. Trials included the EORTC Quality of Life Questionnaire (QLQ-C30), which captures patient-reported HRQL, symptoms, and functioning. Higher scores (range 0-100) indicate better functioning and HRQL. Symptoms were measured with a 4-point scale; not at all to very much. Descriptive statistics were used to analyze diarrhea, PF, and HRQL over time. Results: Patients reporting very much diarrhea at month 3 had worse PF and HRQL compared to patients reporting no diarrhea . The range of difference between patients who reported very much diarrhea and those with none was 8-18 points for PF across trials. For HRQL scores, the range was 13–17 points worse. This trend was also seen in the control arm and at other times. Conclusions: In this set of breast cancer trials with differences in diarrhea by arm, reporting “no meaningful difference in PF or HRQL between the arms” is insufficient and potentially misleading. A more informative interpretation is that an exploratory analysis of HRQL and PF did not show in the investigational arm; there was a greater proportion of patients reporting diarrhea on the treatment arm; and patients reporting more frequent diarrhea reported lower HRQL and PF compared to patients with no diarrhea, regardless of arm. [Table: see text]
Clinical value of atezolizumab + bevacizumab for first-line unresectable hepatocellular carcinoma (HCC): A network meta-analysis.
Authors: Arndt Vogel, Lorenza Rimassa, Hui-Chuan Sun, Ghassan K. Abou-Alfa, Anthony B. El-Khoueiry, David James Pinato, Monica Daigl, Javier Sanchez Alvarez, Panos Orfanos, Michael Leibfried, Marie-Hélène Blanchet Zumofen, Vincent Gaillard, Philippe Merle
Journal: Journal of Clinical Oncology (2020)

4585 Background: The IMbrave150 pivotal study in unresectable HCC showed superiority of atezolizumab + bevacizumab (atezo + bev) vs sorafenib for OS and PFS. Based on these data supporting first-line atezo + bev for HCC, we conducted a network meta-analysis (NMA) to compare the efficacy of atezo + bev with other systemic and local therapies approved for HCC. Methods: A systematic literature review identified randomized controlled trials in adults with locally advanced or metastatic HCC and no prior systemic therapy for HCC. Studies of therapies now approved for any line of HCC treatment with data reported for first-line treatment since sorafenib approval in 2007 were eligible. Screening of 8783 records yielded 55 trials for inclusion; 9 studies were eligible for the evidence network. Reported hazard ratios (HRs) for OS and PFS were extracted from published studies. The IMbrave150, REFLECT and CheckMate-459 study populations were considered sufficiently similar to compare. A generalized linear model with random effects was used to estimate indirect treatment effects. Informative priors for the heterogeneity of treatment effects across trials were adopted given the limited number of trials to inform each pairwise comparison. HRs with 95% credible intervals (CrIs) and Bayesian posterior probability of atezo + bev being superior to other treatments were calculated for each treatment comparison. The base case NMA compared the relative efficacy of atezo + bev vs sorafenib observed in the IMbrave150 study with the relative effect of other therapies. Sensitivity analyses were performed to compare subgroup results as appropriate based on disease etiology, extrahepatic spread and geography. Results: NMA results suggested improved OS with atezo + bev vs lenvatinib (HR, 0.63; 95% CrI: 0.32, 1.25; probability of atezo + bev being superior to lenvatinib: 93.7%) or nivolumab (HR, 0.68; 95% CrI: 0.35, 1.38; probability of atezo + bev being superior to nivolumab: 90.3%) and improved PFS with atezo + bev vs lenvatinib (HR, 0.91; 95% CrI: 0.23, 3.65; probability of atezo + bev being superior to lenvatinib: 61.5%) or nivolumab (HR, 0.63; 95% CrI: 0.16, 2.59; probability of atezo + bev being superior to nivolumab: 85.5%). Conclusions: This NMA suggested greater OS and PFS benefits with first-line atezo + bev treatment vs other therapies approved for treatment of unresectable HCC.
Increased tumor purity and improved biomarker detection using precision needle punch enrichment of pathology specimen paraffin blocks: Method validation and implementation in a prospective clinical trial.
Authors: Jonathan Keith Killian, Chris Wright, Lindsay Chan, Natalie Danziger, Julia Andrea Elvin, Jo-Anne Vergilio, Douglas I. Lin, Erik Abraham Williams, Shakti H. Ramkissoon, Eric Allan Severson, Amanda Hemmerich, Daniel Duncan, Claire I. Edgerly, Julie Y Tse, Kimberly McGregor, Alexa Betzig Schrock, Brian Michael Alexander, Jeffrey S. Ross, Mary Weber Redman, Roy S. Herbst
Journal: Journal of Clinical Oncology (2020)

3622 Background: While many sequencing assays may be geared for short variants (SV), more complex biomarkers such as genomic loss of heterozygosity (gLOH) score, also referred to as homologous recombination deficiency (HRD) score, require higher tumor purity for confident detection. Practical methods to increase tumor nuclei percentage (TN%) from pathology specimens are needed to achieve biomarker results to maximize patient matching to approved therapies and/or clinical trial enrollment. Methods: Tumor purity of specimens was determined by the computational analysis pipeline component of the FDA-approved NGS assay, FoundationOneCDx. In the validation study, specimen purities for each tissue block were compared following either no enrichment (UnE, n=46), pathologist-directed enrichment by straight razor blade (RBE, n=30) or precision needle punch (NPE, n=47). Post-enrichment H&amp;E slides confirmed target region sampled for the NPE arm. Based upon validation data, the needle punch process was implemented for the Lung-MAP prospective clinical trial (LM-NPE). TN% was compared between the first 55 tested LM-NPE specimens and the validation study to assess performance on real-world samples outside of a controlled validation experiment. Results: The mean computational TN% in the 4 groups were: UnE: 33%; RBE: 30%; NPE: 52%; and LM-NPE: 48%. In the validation study, NPE had significantly higher purity than both UnE and RBE (p&lt;0.001); in the trial arm, LM-NPE performed equivalently to NPE (p=0.344). Based upon a 30% tumor purity cutoff, gLOH could be determined for 52% UnE, 50% RBE, 89% NPE and 71% LM-NPE. Comparing NPE and LM-NPE groups reveals no statistical difference in Pass/Fail rates for gLOH determination (p=0.883; Fisher’s Test). Conclusions: Precision needle punch cores from tissue blocks have elevated tumor purity, and consequently, a greater number of successful gLOH determinations. Moreover, this process is rapid and inexpensive. Precision punches may constitute best practice with respect to enriching tumor cells from low-purity specimens for biomarker detection in a routine laboratory specimen-processing setting. [Table: see text]
儿童慢性咳嗽的病因诊断
Authors: 张小宁, 刘恩梅
Journal: BMJ (2011)

咳嗽是机体清除呼吸道分泌物及有害因子的一种防御反射.作为儿童呼吸系统疾病最常见的症状之一[1],7～11岁的儿童中约有9%曾患有慢性咳嗽[2].自2005年中国成人 [1]发表后,儿科界同道十分关注儿童慢性咳嗽的相关问题,相继在国内核心儿科杂志上发表了多篇有关儿童慢性咳嗽的临床研究文章或综述、专家笔谈等[3]。
12-month uptake of PD-L1 testing and atezolizumab (atezo) + <i>nab</i>-paclitaxel (<i>nab</i>-pac) treatment in metastatic triple-negative breast cancer (mTNBC) following accelerated FDA-approval in the United States.
Authors: Leisha A. Emens, Christopher Craggs, Marcio Debiasi, Matthew Kent, Patricia Luhn, Erika Paige Hamilton
Journal: Journal of Clinical Oncology (2020)

e13103 Background: In March 2019, atezo + nab-pac received accelerated FDA-approval for the treatment (tx) of patients (pts) with unresectable locally advanced or metastatic TNBC who express PD-L1 in immune cells (IC), based on the results from the randomized IMpassion130 clinical trial. A companion diagnostic, the Ventana SP142 PD-L1 assay, was concurrently approved. This real-world data analysis describes the uptake of both PD-L1 testing and therapy with atezo + nab-pac from the time of approval. Methods: This is a retrospective study using the Flatiron Health electronic health record (EHR) derived de-identified database, representing &gt; 2.4 million US cancer pts from &gt; 280 cancer clinics. Pts diagnosed with mTNBC starting any line of systemic therapy between March 9, 2019 and December 31, 2019 (to be updated in April 2020 for 12-months follow-up) were included. Two cohorts were examined: pts receiving either atezo-based tx, or tx without atezo. Demographics were described in the pt group overall and by line of therapy (LOT). Steroid tx at baseline was classified as any order/administration of a steroid within the first three administrations of a systemic therapy in a given LOT. Any record of a PD-L1 test was reported. Results: 228 pts diagnosed with mTNBC were included; 65 pts (28%) received any atezo combination, the majority in combination with nab-pac: 57% (n = 37) in first-line (1L), 25% (n = 16) in second-line (2L), and 18% (n = 12) in third-line or later (3L+). Median age at metastatic diagnosis (mDx) for atezo-treated pts was: 1L, 65 y (IQR: 49, 72); 2L, 56 y (IQR: 48, 64); 3L+, 52 y (IQR: 42, 60). Median age at mDx for non-atezo-treated patients was: 1L, 63 y (IQR: 53, 74); 2L, 59 y (IQR: 51, 65); 3L+, 61 y (IQR: 53, 71). Of 228 pts, 158 (69%) had any PD-L1 test recorded. Among atezo-treated pts, 62 (95%) had a documented PD-L1 test; of those 40 (62%) were tested using the SP142 assay. Overall, 205 tests were recorded: SP142, n = 96 (46.8%); unknown/not documented, n = 44 (21.5%); 22C3, n = 36 (17.6%); lab-developed test, n = 26 (12.7%); SP263, n = 2 (1.0%); and 28-8, n = 1, (0.5%). 37 (57%) atezo-treated pts received a steroid at baseline. Conclusions: Atezo tx and testing with SP142 is being implemented following accelerated FDA-approval. A considerable proportion of pts received steroids at baseline and had nab-pac as chemotherapy backbone in clinical practice. Clinical outcomes of atezo-treated pts in the real-world setting remain to be further explored pending longer pt follow-up times.
Hyperbaric oxygen plus Nimodipine for carbon monoxide poisoning
Authors: Jin-e Wan, Pei-song Wang, Shu-zhen Wang, Xue-ling Liu, Qiu-ning
Journal: BMJ (2008)

Four hundred eighty patients with carbon monoxide poisoning were randomly assigned to receive hyperbaric oxygen alone or hyperbaric oxygen plus Nimodipine.Treatment outcomes and the incidence of delayed encephalopathy after acute carbon monoxide poisoning(DEACMP)were observed.We found that the incidence of DEACMP was 14.0％(67/480)in all cases,19.2％(46/67)in hyperbaric oxygen group,and 8.8％(21/67)in hyperbaric oxygen plus Nimodipine group(hyperbaric oxygen group vs hyperbaric oxygen plus Nimodipine group,P＜0.05).These results suggested that hyperbaric oxygen combined with Nimodipine could prevent the development of DEACMP.

Key words: 
Carbon monoxide poisoning; Hyperbaric oxygenation
Preclinical evaluation of WXSH0011, a selective small molecule dual inhibitor of FGFR/c-Met.
Authors: Zhengxia Chen, Meibi Dai, Deheng Sun, Yuanfeng Xia, Yang Zhang, Chi-Chung Chan, Jian Li, Shuhui Chen
Journal: Journal of Clinical Oncology (2020)

e15641 Background: FGFRs (fibroblast growth factor receptors) are a family of receptor tyrosine kinases. c-Met is a receptor tyrosine kinase with a high-affinity ligand, hepatocyte growth factor/scatter factor (HGF/SF). Aberrations in the FGFR pathway are associated with a variety of human cancers. c-Met and HGF have been implicated in carcinogenesis and metastatic tumor progression because of their ability to enhance angiogenesis, cancer cell proliferation, migration, and invasion. WXSH0011 is an orally bioavailable novel potent and selective FGFR/c-Met dual kinase inhibitor, which displayed significant antitumor activity in preclinical models of solid cancer with FGFRs/c-Met overexpression. Preclinical studies demonstrated that WXSH0011 has potential to be effective in solid cancer, such as HCC and Gastric. Methods: Kinase inhibiting activity of WXSH0011 was determined with FGFRs/ c-Met kinase assays. Cellular anti-proliferative activity was evaluated with FGFR overexpressed NCl-H1581, SNU-16, RT112/84, Hep3B, c-Met overexpressed MHCC97H, EBC-1 cell line and FGFR, c-Met both overexpressed PDC cell line (LI-03-0141 (HCC) and ST-02-0063 (Gastric) PDC). The antitumor activity of WXSH0011 was evaluated in vivo cell derived-xenograft (CDX) models of Gastric Cancer SNU-16 and HCC Hep3B. Results: WXSH0011 displayed potent kinase inhibiting activity for FGFR1/2/3/4 and c-Met/ with IC 50 0.19 nM/0.21 nM/1.15 nM/1.49 nM /15.9 nM, respectively. WXSH0011 inhibited cell proliferation in FGFR overexpressed NCl-H1581, SNU-16, RT112/84, Hep3B with IC 50 10 nM, 3 nM, 2 nM, 63 nM, c-Met overexpressed MHCC97H and EBC-1 cell line with IC 50 0.832 µM, 0.52 µM, FGFR, c-Met dual overexpressed LI-03-0141 (HCC) and ST-02-0063 (Gastric) PDC with IC 50 0.19 µM, 0.08 µM. Kinome panel screening revealed that WXSH0011 demonstrated good overall kinase selectivity. WXSH0011 showed antitumor efficacy in gastric cancer SNU-16 (TGI = 100% @5 mpk, BID), as well as in the liver cancer Hep3B model (TGI = 86.92% @20 mpk, QD). Conclusions: We have identified a novel selective and potent dual FGFR/c-Met inhibitor WXSH0011. Preclinical studies shows antitumor efficacy of WXSH0011 in gastric and liver cancer models. It is currently at IND submission stage.
Focus on control of overall cardiovascular risk by improvement of control rate of hypertension
Authors: Yuqing Zhang
Journal: BMJ (2019)

文章简要介绍《高血压基层诊疗指南（2019年）》制订的背景、思路和目标，强调应切实提高高血压控制率，重视对高血压患者的心血管总体风险管理，并对高血压相关的证据不足和争议问题的处理做了补充说明。
Immune checkpoint inhibitors’ (ICI) efficacy according to PD-L1 expression for advanced or metastatic NSCLC: Systematic review and meta-analysis.
Authors: Glauber Maciel, Paula Carlos, Munir Murad Junior, Vânia Eloísa Araújo, Augusto Guerra, Francisco Assis Acúrcio
Journal: Journal of Clinical Oncology (2020)

e21723 Background: Blocking PD-1 pathway has become a milestone in treating many tumors, including non-small cell lung cancer (NSCLC) for first and second line therapies. Although their benefits for some patients, these drugs are not full available in developing countries due to high treatment cost. In this study, we assessed the efficacy of five PD-1 or PD-L1 blockers (nivolumab, pembrolizumab, atezolizumab, durvalumab and avelumab), associated or not to chemotherapy, according to PD-L1 expression. Methods: We performed a systematic review and meta-analysis of randomized clinical trials in the databases MEDLINE/Pubmed, EMBASE, COCHRANE Library and LILACS up to November 2018. We selected trials comparing ICI alone, or associated with ICI or chemotherapy, versus chemotherapy or placebo. Primary outcome was overall survival (OS) and secondary outcome was progression free survival (PFS). Risk of bias of included trials was assessed by Cochrane’s recommended tool and data meta-analysis was performed by Review Manager V5.3 software. Results: We assessed OS and PFS of 12 trials in our meta-analysis. The methodological quality was considered moderate according to Cochrane’s tool. The pooled hazard ratio were 0.70 (95% CI 0.63, 0.78; p &lt; 0.01; I² = 58%) for OS and 0.75 (95% CI 0.64, 0.89; p &lt; 0.01; I² = 88%) for PFS. Subgroup analysis for PD-L1 &lt; 1%, ≥ 1% and ≥ 50% showed OS of 0.78 (95% CI 0.64, 0.95; p = 0.09; I² = 46%), 0.69 (95% CI 0.59, 0.81; p &lt; 0.01; I² = 79%) and 0.57 (95% CI 0.48, 0.68; p = 0.10; I² = 40%), respectively. Data for PFS were 0.85 (95% CI 0.71, 1.03; p = 0.21; I² = 31%), 0.77 (95% CI 0.64, 0.92; p &lt; 0.01; I² = 83%) and 0.53 (95% CI 0.46, 0.62; p = 0.14; I² = 36%), respectively. Conclusions: Our data suggest a dose-response relationship between PD-L1 level and survival outcomes. It was not possible to conduct our meta-analysis by median OS and median PFS difference once these data were not available for every trial we selected. Considering the high price of immune therapy and budget limitations in developing countries’ health system, our findings could optimize health technology assessment agencies recommendations for treating NSCLC with high expression of PD-L1.
The diagnosis and treatment of early postoperative inflammatory ileus
Authors: Long-bo Gong, Hong Xia, tao Song, Xiao-peng L, Liang Meng, Shou-jun Wang
Journal: BMJ (2009)

To investigate the clinical features and principles of diagnosis and treatment of early postoperative inflammatory ileus (EPII). The clinical data of 69 patients with EPII treated in this hospital were retrospectively reviewed. EPII mostly occurred in 3-11d after abdominal surgery, and the average time was 5d. Sixty two cases were cured in a mean period of (22±13)d through combination therapy including gastroenteral decompression, somatostatin, dexamethasone and total parenteral nutrition (TPN). Seven cases were cured by operation. EPII is a special type of early intestinal obstruction which often occurs in two weeks after abdominal operation. Its typical symptoms are abdominal distension; conservative therapy is effective for most cases and reoperation is usually contradicted.

Key words: 
Intestinal obstruction;  Diagnosis
Real-world use of rescue inhaler sensors, electronic symptom questionnaires and physical activity monitors in COPD
Authors: Bowler Russell, Allinder Matthew, Jacobson Sean, Miller Andrew, Miller Bruce, Tal-Singer Ruth, Locantore Nicholas, 崔晓霞
Journal: BMJ (2019)

背景
慢性阻塞性肺疾病(COPD)是一种异质性疾病，其特征是气流阻塞和其他表现，如呼吸道症状、体力活动减少和频繁使用支气管扩张剂。近年来，个人数字监测设备的发展使得COPD患者可以连续收集这些数据，但它们之间的关系尚不清楚。


方法
来自COPD基因队列研究中心的184名受试者同意参与这项为期3周的观察性研究。每位参与者使用智能手机完成每日症状日志（确切地说是慢性肺疾病加重工具），佩戴腕带加速计记录持续的体力活动，并在COPD问卷中完成临床调查表中的体力活动记录。为58名使用定量雾化吸入器(沙丁胺醇)的用户提供了一个吸入传感器，该传感器记录每个吸入动作的时间。


结果
救援吸入器的使用与E-RS-COPD评分密切相关。然而，步长计数与急救应用和E-RS-COPD评分均无相关性。经常无规律的使用吸入器与日常有规律的使用吸入器相比，呼吸道症状更严重，体力活动更少。测量值之间存在很强的逐周相关性，这表明1周的监测足以确定COPD稳定患者的特征。


讨论
该研究强调了实时监测COPD患者的呼吸症状、体力活动和抢救药物的相互作用和相关性。此外，纵向数据的可视化显示这可能有助于疾病管理，有助于推动患者和护理人员之间的对话，以及推动临床试验中基于风险的监测。
Comparison of treatment-related adverse events (TRAE) of different CDK4/6 inhibitors (CDK4/6i) in metastatic breast cancer (MBC): A network meta-analysis.
Authors: Alexandra Desnoyers, Michelle Nadler, Vikaash Kumar, Ramy Saleh, Eitan Amir
Journal: Journal of Clinical Oncology (2020)

e13052 Background: CDK4/6i in combination with endocrine therapy (ET) are a standard of care in hormone receptor positive, HER2 negative MBC. Palbociclib, ribociclib and abemaciclib have all been approved and while efficacy appears similar, differences in safety and tolerability are apparent. Here we quantify TRAEs comparing the 3 CDK4/6i in a network meta-analysis. Methods: We searched PubMed and ASCO and ESMO proceedings to identify randomized trials (RCT) of CDK4/6i. Data on common and serious TRAE were extracted for each approved CDK4/6i. The odd ratio (OR) for each TRAE and the hazard ratio (HR) for progression-free survival (PFS) were calculated relative to ET alone. A network meta-analysis was then performed for each ET backbone (aromatase inhibitor (AI) or fulvestrant) to compare ribociclib and abemaciclib to palbociclib. Results: 7 RCT were included in the analysis and comprised 2715 patients receiving CDK4/6i (palbociclib: 789 patients; ribociclib: 1153 patients; abemaciclib: 773 patients). In 4 RCT (1440 patients) ET backbone was an AI and in 3 RCT (1275 patients) it was fulvestrant. Compared to palbociclib, ribociclib and abemaciclib showed lower grade 3-4 hematological toxicity, but higher GI toxicity (see table). Treatment discontinuation was higher with abemaciclib than other CDK4/6i. Efficacy of the 3 CDK4/6i was similar. Compared to palbociclib, for AI backbone, the HR for PFS for ribociclib was 1.00 and for abemaciclib 1.04. For fulvestrant backbone, the HR were 0.88 and 0.93 respectively. Conclusions: The three approved CDK4/6i show comparable efficacy, but differences in safety and tolerability. Abemaciclib has worse tolerability with significantly higher treatment discontinuation likely due to gastro-intestinal toxicity. [Table: see text]