{"title":"Overseas doctor recruitment saved NHS £10.9bn but UK is failing to train homegrown talent, say MPs.","authors":"Adrian O'Dowd","doi":"10.1136/bmj.s508","DOIUrl":"https://doi.org/10.1136/bmj.s508","url":null,"abstract":"","PeriodicalId":22388,"journal":{"name":"The BMJ","volume":"49 1","pages":"s508"},"PeriodicalIF":0.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVETo report updated results of the phase 3 PHILA trial, which evaluated the efficacy and safety of pyrotinib or placebo in combination with trastuzumab and docetaxel in patients with untreated human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer.DESIGNMulticentre, double blind, randomised, placebo controlled phase 3 trial.SETTING40 centres in China, 6 May 2019 to 17 January 2022.PARTICIPANTS590 female patients with untreated HER2 positive metastatic breast cancer.INTERVENTIONSEligible patients were randomly assigned in a 1:1 ratio to receive either the irreversible pan-HER inhibitor pyrotinib (400 mg orally once daily) or placebo, both in combination with intravenous trastuzumab (8 mg/kg for the first cycle, then 6 mg/kg in subsequent cycles) and docetaxel (75 mg/m2) on day 1 of each 21 day treatment cycle.MAIN OUTCOME MEASUREThe primary endpoint was investigator assessed progression-free survival.RESULTS590 patients were randomised and received treatment (297 in the pyrotinib group and 293 in the placebo group). As of 30 April 2024, during a median follow-up of 35.7 months in the pyrotinib group and 34.3 months in the placebo group, 59 (20%) and 87 (30%) patients died, respectively. Overall survival was longer in the pyrotinib group (hazard ratio 0.64 (95% confidence interval (CI) 0.46 to 0.89); nominal one-sided P=0.004). At end of follow-up, neither group had reached the median overall survival. Improvement in progression-free survival in the pyrotinib group was maintained (22.1 months (95% CI 19.3 to 27.8) v 10.5 months (9.5 to 12.4), hazard ratio 0.44 (95% CI 0.36 to 0.53); nominal one sided P<0.001). Adverse event profiles remained consistent with the interim analysis for type, frequency, and severity. After discontinuation of docetaxel, the overall incidence of adverse events decreased substantially. As of 30 May 2025, with a median follow-up of 45.5 months, the pyrotinib based regimen showed consistent and prolonged survival benefit.CONCLUSIONSThe updated analysis of the phase 3 PHILA trial confirmed the superiority of pyrotinib in combination with trastuzumab and docetaxel over placebo in combination with trastuzumab and docetaxel in sustaining longer progression-free survival and improving overall survival for initial treatment of HER2 positive metastatic breast cancer. The safety profile remained consistent with interim findings, with no new safety signals identified during extended follow-up. This analysis reinforces the efficacy of this dual anti-HER2 (pyrotinib plus trastuzumab) regimen as an effective treatment strategy for this patient population.TRIAL REGISTRATIONClinicalTrials.gov NCT03863223.
目的：报告最新的3期PHILA试验结果，该试验评估了pyrotinib或安慰剂联合曲妥珠单抗和多西他赛治疗未经治疗的人表皮生长因子受体2 （HER2）阳性转移性乳腺癌患者的疗效和安全性。设计多中心、双盲、随机、安慰剂对照的3期试验。2019年5月6日至2022年1月17日在中国设立40个中心。参与者：s590例未经治疗的HER2阳性转移性乳腺癌女性患者。符合干预条件的患者以1:1的比例随机分配，接受不可逆泛her抑制剂pyrotinib （400 mg口服，每日一次）或安慰剂，在每21天治疗周期的第1天联合静脉注射曲妥珠单抗（第一个周期为8 mg/kg，随后周期为6 mg/kg）和多西他赛（75 mg/m2）。主要结局测量：主要终点是研究者评估的无进展生存期。结果590例患者被随机分配并接受治疗（pyrotinib组297例，安慰剂组293例）。截至2024年4月30日，在pyrotinib组35.7个月和安慰剂组34.3个月的中位随访期间，分别有59例（20%）和87例（30%）患者死亡。吡罗替尼组总生存期更长(风险比0.64(95%可信区间（CI） 0.46 ~ 0.89)；名义单侧P=0.004)。在随访结束时，两组患者均未达到中位总生存期。吡罗替尼组无进展生存期的改善得到维持(22.1个月（95% CI 19.3 ~ 27.8） vs 10.5个月（9.5 ~ 12.4），风险比0.44 (95% CI 0.36 ~ 0.53)；名义单侧P<0.001)。不良事件的类型、频率和严重程度与中期分析一致。停药后，不良事件的总体发生率显著下降。截至2025年5月30日，中位随访时间为45.5个月，以吡罗替尼为基础的方案显示出一致和延长的生存获益。3期PHILA试验的最新分析证实，在HER2阳性转移性乳腺癌初始治疗中，pyrotinib联合曲妥珠单抗和多西他赛比安慰剂联合曲妥珠单抗和多西他赛在维持更长的无进展生存期和提高总生存期方面具有优势。安全性概况与中期调查结果一致，在延长随访期间未发现新的安全信号。该分析强化了这种双重抗her2 （pyrotinib +曲妥珠单抗）方案作为该患者群体有效治疗策略的有效性。临床试验注册。gov NCT03863223。
{"title":"Pyrotinib or placebo in combination with trastuzumab and docetaxel for HER2 positive metastatic breast cancer: long term survival results from randomised phase 3 PHILA trial.","authors":"Fei Ma,Min Yan,Wei Li,Quchang Ouyang,Zhongsheng Tong,Yuee Teng,Yongsheng Wang,Shusen Wang,Cuizhi Geng,Ting Luo,Jincai Zhong,Qingyuan Zhang,Qiang Liu,Xiaohua Zeng,Tao Sun,Qinguo Mo,Shoubing Zhou,Peidong Li,Jing Cheng,Xiaojia Wang,Jianyun Nie,Jin Yang,Xinhong Wu,Xinshuai Wang,Huiping Li,Guangyu Yao,Yang Fan,Jiaman Lin,Xiaoyu Zhu,Binghe Xu","doi":"10.1136/bmj-2025-087259","DOIUrl":"https://doi.org/10.1136/bmj-2025-087259","url":null,"abstract":"OBJECTIVETo report updated results of the phase 3 PHILA trial, which evaluated the efficacy and safety of pyrotinib or placebo in combination with trastuzumab and docetaxel in patients with untreated human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer.DESIGNMulticentre, double blind, randomised, placebo controlled phase 3 trial.SETTING40 centres in China, 6 May 2019 to 17 January 2022.PARTICIPANTS590 female patients with untreated HER2 positive metastatic breast cancer.INTERVENTIONSEligible patients were randomly assigned in a 1:1 ratio to receive either the irreversible pan-HER inhibitor pyrotinib (400 mg orally once daily) or placebo, both in combination with intravenous trastuzumab (8 mg/kg for the first cycle, then 6 mg/kg in subsequent cycles) and docetaxel (75 mg/m2) on day 1 of each 21 day treatment cycle.MAIN OUTCOME MEASUREThe primary endpoint was investigator assessed progression-free survival.RESULTS590 patients were randomised and received treatment (297 in the pyrotinib group and 293 in the placebo group). As of 30 April 2024, during a median follow-up of 35.7 months in the pyrotinib group and 34.3 months in the placebo group, 59 (20%) and 87 (30%) patients died, respectively. Overall survival was longer in the pyrotinib group (hazard ratio 0.64 (95% confidence interval (CI) 0.46 to 0.89); nominal one-sided P=0.004). At end of follow-up, neither group had reached the median overall survival. Improvement in progression-free survival in the pyrotinib group was maintained (22.1 months (95% CI 19.3 to 27.8) v 10.5 months (9.5 to 12.4), hazard ratio 0.44 (95% CI 0.36 to 0.53); nominal one sided P<0.001). Adverse event profiles remained consistent with the interim analysis for type, frequency, and severity. After discontinuation of docetaxel, the overall incidence of adverse events decreased substantially. As of 30 May 2025, with a median follow-up of 45.5 months, the pyrotinib based regimen showed consistent and prolonged survival benefit.CONCLUSIONSThe updated analysis of the phase 3 PHILA trial confirmed the superiority of pyrotinib in combination with trastuzumab and docetaxel over placebo in combination with trastuzumab and docetaxel in sustaining longer progression-free survival and improving overall survival for initial treatment of HER2 positive metastatic breast cancer. The safety profile remained consistent with interim findings, with no new safety signals identified during extended follow-up. This analysis reinforces the efficacy of this dual anti-HER2 (pyrotinib plus trastuzumab) regimen as an effective treatment strategy for this patient population.TRIAL REGISTRATIONClinicalTrials.gov NCT03863223.","PeriodicalId":22388,"journal":{"name":"The BMJ","volume":"52 1","pages":"e087259"},"PeriodicalIF":0.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New risk prediction model for managing COPD in primary care.","authors":"Taavi Tillmann,Milo A Puhan","doi":"10.1136/bmj.s464","DOIUrl":"https://doi.org/10.1136/bmj.s464","url":null,"abstract":"","PeriodicalId":22388,"journal":{"name":"The BMJ","volume":"12 1","pages":"s464"},"PeriodicalIF":0.0,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Patients at risk from new \"advice and guidance\" referral rules, GP leaders warn.","authors":"Gareth Iacobucci","doi":"10.1136/bmj.s492","DOIUrl":"https://doi.org/10.1136/bmj.s492","url":null,"abstract":"","PeriodicalId":22388,"journal":{"name":"The BMJ","volume":"17 1","pages":"s492"},"PeriodicalIF":0.0,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Misinformation \"infodemic\": Doctors need \"humility\" when tackling patient concerns, say experts.","authors":"Gareth Iacobucci","doi":"10.1136/bmj.s493","DOIUrl":"https://doi.org/10.1136/bmj.s493","url":null,"abstract":"","PeriodicalId":22388,"journal":{"name":"The BMJ","volume":"17 1","pages":"s493"},"PeriodicalIF":0.0,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Relentless rises in radiology workloads cannot be solved by the radiology department alone.","authors":"Giles Maskell","doi":"10.1136/bmj.s487","DOIUrl":"https://doi.org/10.1136/bmj.s487","url":null,"abstract":"","PeriodicalId":22388,"journal":{"name":"The BMJ","volume":"31 1","pages":"s487"},"PeriodicalIF":0.0,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abu-Sitta case: New regulator joins appeal effort on doctor cleared of supporting terrorism.","authors":"Clare Dyer","doi":"10.1136/bmj.s495","DOIUrl":"https://doi.org/10.1136/bmj.s495","url":null,"abstract":"","PeriodicalId":22388,"journal":{"name":"The BMJ","volume":"16 1","pages":"s495"},"PeriodicalIF":0.0,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"When I use a word . . . Facial blindness-prosopagnosia.","authors":"Jeffrey K Aronson","doi":"10.1136/bmj.s494","DOIUrl":"https://doi.org/10.1136/bmj.s494","url":null,"abstract":"","PeriodicalId":22388,"journal":{"name":"The BMJ","volume":"271 1","pages":"s494"},"PeriodicalIF":0.0,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Iran war: 43 attacks on healthcare facilities in Iran and Lebanon, WHO says, as thousands killed.","authors":"Elisabeth Mahase","doi":"10.1136/bmj.s484","DOIUrl":"https://doi.org/10.1136/bmj.s484","url":null,"abstract":"","PeriodicalId":22388,"journal":{"name":"The BMJ","volume":"1 1","pages":"s484"},"PeriodicalIF":0.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antimicrobial resistance: Pharma pipeline projects drop by over a third.","authors":"Elisabeth Mahase","doi":"10.1136/bmj.s479","DOIUrl":"https://doi.org/10.1136/bmj.s479","url":null,"abstract":"","PeriodicalId":22388,"journal":{"name":"The BMJ","volume":"57 1","pages":"s479"},"PeriodicalIF":0.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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