Pub Date : 2024-09-01Epub Date: 2024-08-12DOI: 10.1016/S1470-2045(24)00338-3
Emanuel Bührer, Michal Kicinski, Mario Mandala, Madeline Pe, Georgina V Long, Victoria Atkinson, Christian U Blank, Andrew Haydon, Stéphane Dalle, Adnan Khattak, Matteo S Carlino, Andrey Meshcheryakov, Shahneen Sandhu, Susana Puig, Dirk Schadendorf, Rahima Jamal, Piotr Rutkowski, Alfonsus J M van den Eertwegh, Corneel Coens, Dmitri Grebennik, Clemens Krepler, Caroline Robert, Alexander M M Eggermont
<p><strong>Background: </strong>In the European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 study, adjuvant pembrolizumab improved recurrence-free survival and distant-metastasis-free survival in patients with resected stage III melanoma. Earlier results showed no effect of pembrolizumab on health-related quality of life (HRQOL). Little is known about HRQOL after completion of treatment with pembrolizumab, an important research area concerning patients who are likely to become long-term survivors. This study reports long-term HRQOL results.</p><p><strong>Methods: </strong>This double-blind, randomised, controlled, phase 3 trial compared adjuvant pembrolizumab with placebo in patients aged 18 years or older with previously untreated stage IIIA, IIIB, or IIIC resected cutaneous melanoma and an Eastern Cooperative Oncology Group performance status score of 1 or 0, recruited from 123 academic centres and community hospitals in 23 countries. Patients were randomly assigned (1:1) with a minimisation technique stratified for stage and geographical region to receive 200 mg of intravenous pembrolizumab or placebo every 3 weeks for up to 18 doses. Investigators, patients, and those collecting or analysing data were masked to group assignment. The primary endpoint of the trial was recurrence-free survival (reported elsewhere). HRQOL was a prespecified exploratory endpoint, measured with the EORTC Quality of Life Questionnaire-Core 30. All patients with a baseline HRQOL evaluation available who were alive 108 weeks from randomisation were included in this analysis of long-term HRQOL. Long-term HRQOL included assessments measured every 6 months between 108 weeks and 48 months after randomisation. The threshold of clinical relevance for all HRQOL scales used was an average change of 5 points. The trial is ongoing, recruitment is completed, and HRQOL data collection is finalised. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37.</p><p><strong>Findings: </strong>Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were randomly assigned to pembrolizumab (n=514) or placebo (n=505). Completion of the HRQOL evaluation at baseline exceeded 90% (481 [94%] patients in the pembrolizumab group and 467 [92%] in the placebo group), and ranged between 60% and 90% for post-baseline timepoints. Among patients with a baseline HRQOL evaluation, 365 (39%) were female and 583 (61%) were male. The mean change from baseline to long-term HRQOL was -0·56 (95% CI -2·33 to 1·22) in the pembrolizumab group and 1·63 (-0·12 to 3·38) in the placebo group. The difference between the two groups was -2·19 (-4·65 to 0·27, p=0·081). Differences for all other scales were smaller than 5 and not statistically significant.</p><p><strong>Interpretation: </strong>Adjuvant pembrolizumab did not have a significant impact on long-term HRQOL compared with placebo in patients with resected stage III melanoma. These findings, tog
{"title":"Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): long-term, health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial.","authors":"Emanuel Bührer, Michal Kicinski, Mario Mandala, Madeline Pe, Georgina V Long, Victoria Atkinson, Christian U Blank, Andrew Haydon, Stéphane Dalle, Adnan Khattak, Matteo S Carlino, Andrey Meshcheryakov, Shahneen Sandhu, Susana Puig, Dirk Schadendorf, Rahima Jamal, Piotr Rutkowski, Alfonsus J M van den Eertwegh, Corneel Coens, Dmitri Grebennik, Clemens Krepler, Caroline Robert, Alexander M M Eggermont","doi":"10.1016/S1470-2045(24)00338-3","DOIUrl":"10.1016/S1470-2045(24)00338-3","url":null,"abstract":"<p><strong>Background: </strong>In the European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 study, adjuvant pembrolizumab improved recurrence-free survival and distant-metastasis-free survival in patients with resected stage III melanoma. Earlier results showed no effect of pembrolizumab on health-related quality of life (HRQOL). Little is known about HRQOL after completion of treatment with pembrolizumab, an important research area concerning patients who are likely to become long-term survivors. This study reports long-term HRQOL results.</p><p><strong>Methods: </strong>This double-blind, randomised, controlled, phase 3 trial compared adjuvant pembrolizumab with placebo in patients aged 18 years or older with previously untreated stage IIIA, IIIB, or IIIC resected cutaneous melanoma and an Eastern Cooperative Oncology Group performance status score of 1 or 0, recruited from 123 academic centres and community hospitals in 23 countries. Patients were randomly assigned (1:1) with a minimisation technique stratified for stage and geographical region to receive 200 mg of intravenous pembrolizumab or placebo every 3 weeks for up to 18 doses. Investigators, patients, and those collecting or analysing data were masked to group assignment. The primary endpoint of the trial was recurrence-free survival (reported elsewhere). HRQOL was a prespecified exploratory endpoint, measured with the EORTC Quality of Life Questionnaire-Core 30. All patients with a baseline HRQOL evaluation available who were alive 108 weeks from randomisation were included in this analysis of long-term HRQOL. Long-term HRQOL included assessments measured every 6 months between 108 weeks and 48 months after randomisation. The threshold of clinical relevance for all HRQOL scales used was an average change of 5 points. The trial is ongoing, recruitment is completed, and HRQOL data collection is finalised. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37.</p><p><strong>Findings: </strong>Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were randomly assigned to pembrolizumab (n=514) or placebo (n=505). Completion of the HRQOL evaluation at baseline exceeded 90% (481 [94%] patients in the pembrolizumab group and 467 [92%] in the placebo group), and ranged between 60% and 90% for post-baseline timepoints. Among patients with a baseline HRQOL evaluation, 365 (39%) were female and 583 (61%) were male. The mean change from baseline to long-term HRQOL was -0·56 (95% CI -2·33 to 1·22) in the pembrolizumab group and 1·63 (-0·12 to 3·38) in the placebo group. The difference between the two groups was -2·19 (-4·65 to 0·27, p=0·081). Differences for all other scales were smaller than 5 and not statistically significant.</p><p><strong>Interpretation: </strong>Adjuvant pembrolizumab did not have a significant impact on long-term HRQOL compared with placebo in patients with resected stage III melanoma. These findings, tog","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":" ","pages":"1202-1212"},"PeriodicalIF":41.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-02DOI: 10.1016/S1470-2045(24)00334-6
Nicoletta Colombo, Elena Biagioli, Kenichi Harano, Francesca Galli, Emma Hudson, Yoland Antill, Chel Hun Choi, Manuela Rabaglio, Frederic Marmé, Christian Marth, Gabriella Parma, Lorena Fariñas-Madrid, Shin Nishio, Karen Allan, Yeh Chen Lee, Elisa Piovano, Beatriz Pardo, Satoshi Nakagawa, John McQueen, Claudio Zamagni, Luis Manso, Kazuhiro Takehara, Giulia Tasca, Annamaria Ferrero, Germana Tognon, Andrea Alberto Lissoni, Mariacristina Petrella, Maria Elena Laudani, Eliana Rulli, Sara Uggeri, M Pilar Barretina Ginesta
<p><strong>Background: </strong>At the time of AtTEnd trial design, standard treatment for advanced or recurrent endometrial cancer included carboplatin and paclitaxel chemotherapy. This trial assessed whether combining atezolizumab with chemotherapy might improve outcomes in this population.</p><p><strong>Methods: </strong>AtTEnd was a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial done in 89 hospitals in 11 countries across Europe, Australia, New Zealand, and Asia. Enrolled patients were aged 18 years or older, and had advanced or recurrent endometrial carcinoma or carcinosarcoma, an Eastern Cooperative Oncology Group performance status of 0-2, and received no previous systemic chemotherapy for recurrence. Patients were randomly assigned (2:1) using an interactive web response system (block size of six) to either atezolizumab 1200 mg or placebo given intravenously with chemotherapy (carboplatin at area under the curve of 5 or 6 and paclitaxel 175 mg/m<sup>2</sup> intravenously on day 1 every 21 days) for 6-8 cycles, then continued until progression. Stratification factors were country, histological subtype, advanced or recurrent status, and mismatch repair (MMR) status. Participants and treating clinicians were masked to group allocation. The hierarchically tested co-primary endpoints were progression-free survival (in patients with MMR-deficient [dMMR] tumours, and in the overall population) and overall survival (in the overall population). Primary analyses were done in the intention-to-treat population, defined as all randomly assigned patients who gave their full consent to participation in the study and data processing. Safety was assessed in all patients included in the intention-to-treat population who received at least one dose of study treatment. Here, we report the primary progression-free survival and the interim overall survival results. This study is ongoing and is registered with ClinicalTrials.gov, NCT03603184.</p><p><strong>Findings: </strong>Between Oct 3, 2018, and Jan 7, 2022, 551 patients were randomly assigned to atezolizumab (n=362) or placebo (n=189). Two patients in the atezolizumab group were excluded from all analyses due to lack of consent. Median follow-up was 28·3 months (IQR 21·2-37·6). 81 (23%) patients in the atezolizumab group and 44 (23%) patients in the placebo group had dMMR disease by central assessment. In the dMMR population, median progression-free survival was not estimable (95% CI 12·4 months-not estimable [NE]) in the atezolizumab group and 6·9 months (6·3-10·1) in the placebo group (hazard ratio [HR] 0·36, 95% CI 0·23-0·57; p=0·0005). In the overall population, median progression-free survival was 10·1 months (95% CI 9·5-12·3) in the atezolizumab group and 8·9 months (8·1-9·6) in the placebo group (HR 0·74, 95% CI 0·61-0·91; p=0·022). Median overall survival was 38·7 months (95% CI 30·6-NE) in the atezolizumab group and 30·2 months (25·0-37·2) in the placebo group (HR 0·82, 95
背景：在设计AtTEnd试验时，晚期或复发性子宫内膜癌的标准治疗包括卡铂和紫杉醇化疗。该试验评估了将阿特珠单抗与化疗相结合是否能改善这一人群的治疗效果：AtTEnd是一项多中心、双盲、随机、安慰剂对照的3期试验，在欧洲、澳大利亚、新西兰和亚洲11个国家的89家医院进行。入组患者年龄在18岁或以上，患有晚期或复发性子宫内膜癌或癌肉瘤，东部合作肿瘤学组表现为0-2级，既往未因复发接受过系统化疗。患者通过交互式网络响应系统（每组6人）被随机分配（2:1）至阿替佐珠单抗1200毫克或安慰剂，同时静脉注射化疗药物（卡铂曲线下面积为5或6，紫杉醇175毫克/平方米，静脉注射，每21天1天），共6-8个周期，然后继续治疗直至病情恶化。分层因素包括国家、组织学亚型、晚期或复发状态以及错配修复（MMR）状态。参与者和主治临床医生均被蒙蔽，不知道分组情况。分层测试的共同主要终点是无进展生存期（MMR缺陷[dMMR]肿瘤患者和总体人群）和总生存期（总体人群）。主要分析是在意向治疗人群中进行的，意向治疗人群是指所有随机分配并完全同意参与研究和数据处理的患者。对所有纳入意向治疗人群并至少接受过一次治疗的患者进行了安全性评估。我们在此报告主要无进展生存期和中期总生存期结果。这项研究正在进行中，已在ClinicalTrials.gov上注册，编号为NCT03603184.研究结果：2018年10月3日至2022年1月7日期间，551名患者被随机分配到atezolizumab（n=362）或安慰剂（n=189）。atezolizumab组的两名患者因未获得同意而被排除在所有分析之外。中位随访时间为 28-3 个月（IQR 21-2-37-6）。经中心评估，阿特珠单抗组中有 81 例（23%）患者患有 dMMR 疾病，安慰剂组中有 44 例（23%）患者患有 dMMR 疾病。在dMMR人群中，atezolizumab组的中位无进展生存期无法估计（95% CI 12-4个月-无法估计[NE]），安慰剂组为6-9个月（6-3-10-1）（危险比[HR]0-36，95% CI 0-23-0-57；P=0-0005）。在总体人群中，atezolizumab组的中位无进展生存期为10-1个月（95% CI 9-5-12-3），安慰剂组为8-9个月（8-1-9-6）（HR 0-74，95% CI 0-61-0-91；P=0-022）。阿特珠单抗组的中位总生存期为38-7个月（95% CI 30-6-NE），安慰剂组为30-2个月（25-0-37-2）（HR 0-82，95% CI 0-63-1-07；对数秩p=0-048）。总生存期中期分析的 p 值未超过停止界限；因此，试验将继续进行，直至记录到所需的事件数。最常见的3-4级不良事件是中性粒细胞减少症（阿替佐珠单抗组356名患者中有97人[27%]，安慰剂组185名患者中有51人[28%]）和贫血（49人[14%]，安慰剂组24人[13%]）。atezolizumab组有46名患者（13%）发生了与治疗相关的严重不良事件，安慰剂组有6名患者（3%）发生了与治疗相关的严重不良事件。有两名患者发生了与治疗相关的死亡（两组各有一名患者死于肺炎）：atezolizumab联合化疗提高了晚期或复发性子宫内膜癌患者的无进展生存期，尤其是在dMMR癌患者中，这表明在标准化疗的基础上，atezolizumab可作为这一特殊亚组的一线治疗药物：F Hoffmann-La Roche.
{"title":"Atezolizumab and chemotherapy for advanced or recurrent endometrial cancer (AtTEnd): a randomised, double-blind, placebo-controlled, phase 3 trial.","authors":"Nicoletta Colombo, Elena Biagioli, Kenichi Harano, Francesca Galli, Emma Hudson, Yoland Antill, Chel Hun Choi, Manuela Rabaglio, Frederic Marmé, Christian Marth, Gabriella Parma, Lorena Fariñas-Madrid, Shin Nishio, Karen Allan, Yeh Chen Lee, Elisa Piovano, Beatriz Pardo, Satoshi Nakagawa, John McQueen, Claudio Zamagni, Luis Manso, Kazuhiro Takehara, Giulia Tasca, Annamaria Ferrero, Germana Tognon, Andrea Alberto Lissoni, Mariacristina Petrella, Maria Elena Laudani, Eliana Rulli, Sara Uggeri, M Pilar Barretina Ginesta","doi":"10.1016/S1470-2045(24)00334-6","DOIUrl":"10.1016/S1470-2045(24)00334-6","url":null,"abstract":"<p><strong>Background: </strong>At the time of AtTEnd trial design, standard treatment for advanced or recurrent endometrial cancer included carboplatin and paclitaxel chemotherapy. This trial assessed whether combining atezolizumab with chemotherapy might improve outcomes in this population.</p><p><strong>Methods: </strong>AtTEnd was a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial done in 89 hospitals in 11 countries across Europe, Australia, New Zealand, and Asia. Enrolled patients were aged 18 years or older, and had advanced or recurrent endometrial carcinoma or carcinosarcoma, an Eastern Cooperative Oncology Group performance status of 0-2, and received no previous systemic chemotherapy for recurrence. Patients were randomly assigned (2:1) using an interactive web response system (block size of six) to either atezolizumab 1200 mg or placebo given intravenously with chemotherapy (carboplatin at area under the curve of 5 or 6 and paclitaxel 175 mg/m<sup>2</sup> intravenously on day 1 every 21 days) for 6-8 cycles, then continued until progression. Stratification factors were country, histological subtype, advanced or recurrent status, and mismatch repair (MMR) status. Participants and treating clinicians were masked to group allocation. The hierarchically tested co-primary endpoints were progression-free survival (in patients with MMR-deficient [dMMR] tumours, and in the overall population) and overall survival (in the overall population). Primary analyses were done in the intention-to-treat population, defined as all randomly assigned patients who gave their full consent to participation in the study and data processing. Safety was assessed in all patients included in the intention-to-treat population who received at least one dose of study treatment. Here, we report the primary progression-free survival and the interim overall survival results. This study is ongoing and is registered with ClinicalTrials.gov, NCT03603184.</p><p><strong>Findings: </strong>Between Oct 3, 2018, and Jan 7, 2022, 551 patients were randomly assigned to atezolizumab (n=362) or placebo (n=189). Two patients in the atezolizumab group were excluded from all analyses due to lack of consent. Median follow-up was 28·3 months (IQR 21·2-37·6). 81 (23%) patients in the atezolizumab group and 44 (23%) patients in the placebo group had dMMR disease by central assessment. In the dMMR population, median progression-free survival was not estimable (95% CI 12·4 months-not estimable [NE]) in the atezolizumab group and 6·9 months (6·3-10·1) in the placebo group (hazard ratio [HR] 0·36, 95% CI 0·23-0·57; p=0·0005). In the overall population, median progression-free survival was 10·1 months (95% CI 9·5-12·3) in the atezolizumab group and 8·9 months (8·1-9·6) in the placebo group (HR 0·74, 95% CI 0·61-0·91; p=0·022). Median overall survival was 38·7 months (95% CI 30·6-NE) in the atezolizumab group and 30·2 months (25·0-37·2) in the placebo group (HR 0·82, 95","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":" ","pages":"1135-1146"},"PeriodicalIF":41.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-07DOI: 10.1016/S1470-2045(24)00391-7
Hans-Christian Kolberg, Cornelia Kolberg-Liedtke
{"title":"Who does not benefit from whole-breast radiotherapy and how to find them?","authors":"Hans-Christian Kolberg, Cornelia Kolberg-Liedtke","doi":"10.1016/S1470-2045(24)00391-7","DOIUrl":"10.1016/S1470-2045(24)00391-7","url":null,"abstract":"","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":" ","pages":"1110-1111"},"PeriodicalIF":41.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/S1470-2045(24)00373-5
Mafalda Oliveira, Hope S Rugo, Sacha J Howell, Florence Dalenc, Javier Cortes, Henry L Gomez, Xichun Hu, Masakazu Toi, Komal Jhaveri, Petr Krivorotko, Sibylle Loibl, Serafin Morales Murillo, Meena Okera, Zbigniew Nowecki, Yeon Hee Park, Joo Hyuk Sohn, Eriko Tokunaga, Samih Yousef, Lyudmila Zhukova, Marta Fulford, Haylee Andrews, Ian Wadsworth, Celina D'Cruz, Nicholas C Turner
<p><strong>Background: </strong>CAPItello-291 is an ongoing phase 3 trial in which capivasertib-fulvestrant significantly improved progression-free survival versus placebo-fulvestrant in patients with hormone receptor-positive, HER2-negative advanced breast cancer who had relapse or disease progression during or after aromatase inhibitor treatment, in both the overall population and in patients with PIK3CA, AKT1, or PTEN-altered tumours. This study further explored patient-reported health-related quality of life (HRQOL), functioning, symptoms, and symptom tolerability in CAPItello-291.</p><p><strong>Methods: </strong>This phase 3, randomised, double-blind, placebo-controlled trial, which was conducted across 193 hospitals and cancer centres in 19 countries, enrolled women with any menopausal status or men, aged ≥18 years (≥20 years in Japan), with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer who had relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase (CDK) 4 or 6 inhibitor therapy. Patients had an Eastern Cooperative Oncology Group/WHO performance score of 0 or 1 and could have received up to two previous lines of endocrine therapy and up to one previous line of chemotherapy for advanced disease. Patients were randomly assigned (1:1) using block randomisation (stratified according to the presence or absence of liver metastases, previous use of a CDK4/6 inhibitor [yes vs no], and geographical region) to receive oral capivasertib 400 mg (twice daily for 4 days, followed by 3 days off) plus intramuscular fulvestrant 500 mg (every 14 days for the first three injections, then every 28 days) or placebo with matching fulvestrant dosing. The dual primary endpoint of the trial was investigator-assessed progression-free survival assessed both in the overall population and among patients with PIK3CA, AKT1, or PTEN-altered tumours. The EORTC Quality of Life Questionnaire 30-item core module (QLQ-C30) and breast module (QLQ-BR23), Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and Patient Global Impression of Treatment Tolerability (PGI-TT) questionnaires were used to assess patient-reported outcomes. Evaluation of EORTC QLQ-C30 and EORTC QLQ-BR23 were secondary endpoints and evaluation of PRO-CTCAE and PGI-TT were pre-defined exploratory endpoints, and these endpoints are the subject of analysis in this Article. Data were collected at baseline and prespecified timepoints. Patient-reported outcomes were analysed in all randomly assigned patients with an evaluable baseline assessment and at least one evaluable post-baseline assessment. Change from baseline was assessed using mixed model with repeated measures for EORTC QLQ-C30 and summarised for QLQ-BR23. Time to deterioration was described using the Kaplan-Meier method. PGI-TT and PRO-CTCAE responses were summarised at each treatment
研究背景CAPItello-291是一项正在进行的3期试验，对于激素受体阳性、HER2阴性、在芳香化酶抑制剂治疗期间或治疗后复发或疾病进展的晚期乳腺癌患者，卡匹伐他汀-氟维司群与安慰剂-氟维司群相比，在总体人群和PIK3CA、AKT1或PTEN改变的肿瘤患者中均可显著改善无进展生存期。本研究进一步探讨了CAPItello-291患者报告的健康相关生活质量（HRQOL）、功能、症状和症状耐受性：这项3期随机、双盲、安慰剂对照试验在19个国家的193家医院和癌症中心进行，招募了年龄≥18岁（日本≥20岁）、激素受体阳性、HER2阴性的局部晚期或转移性乳腺癌患者，这些患者在接受芳香化酶抑制剂治疗期间或治疗后复发或疾病进展，无论之前是否接受过细胞周期蛋白依赖性激酶（CDK）4或6抑制剂治疗。患者的东部合作肿瘤学组/世卫组织表现评分为0分或1分，曾接受过最多两种内分泌疗法和最多一种晚期化疗。患者通过整群随机分配（1:1）（根据有无肝转移、既往是否使用过CDK4/6抑制剂[是与否]以及地理区域进行分层）接受口服卡匹伐替布400毫克（每天两次，共4天，之后休息3天）加肌肉注射氟维司群500毫克（前3次注射每14天一次，之后每28天一次）或安慰剂，氟维司群剂量与之匹配。试验的双重主要终点是研究者评估的无进展生存期，评估对象既包括总体患者，也包括PIK3CA、AKT1或PTEN改变的肿瘤患者。EORTC生活质量问卷30项核心模块（QLQ-C30）和乳腺模块（QLQ-BR23）、不良事件通用术语标准患者报告结果版（PRO-CTCAE）和治疗耐受性患者总体印象（PGI-TT）问卷用于评估患者报告结果。EORTC QLQ-C30 和 EORTC QLQ-BR23 的评估是次要终点，PRO-CTCAE 和 PGI-TT 的评估是预先确定的探索性终点，这些终点是本文分析的主题。在基线和预先规定的时间点收集数据。对所有随机分配的患者的患者报告结果进行了分析，这些患者均有可评估的基线评估和至少一次可评估的基线后评估。对 EORTC QLQ-C30 采用重复测量混合模型评估与基线相比的变化，对 QLQ-BR23 则进行总结。恶化时间采用 Kaplan-Meier 法进行描述。对每个治疗周期的 PGI-TT 和 PRO-CTCAE 反应进行了总结。患者报告的结果不具备前瞻性的统计比较能力。该试验已在 ClinicalTrials.gov 注册，编号为 NCT04305496：2020年6月2日至2021年10月13日期间，901名患者入组，其中708名患者被随机分配接受卡匹伐他汀-氟维司群（355人）或安慰剂-氟维司群（353人）治疗。卡匹伐他汀-氟维司群组患者的中位年龄为59岁（IQR 51-67），安慰剂-氟维司群组患者的中位年龄为58岁（IQR 49-66）。在数据截止日（2022年8月15日），在总体人群中，卡匹伐他汀-氟维司群的无进展生存期中位随访时间为13-0个月（IQR 9-1-16-7），安慰剂-氟维司群的无进展生存期中位随访时间为12-7个月（IQR 2-0-16-4）。在整个研究期间，EORTC QLQ-C30总体健康状况/生活质量（GHS/QOL）评分与基线相比保持不变，且治疗组之间的评分相似（卡维昔替布-氟维司群与安慰剂-氟维司群相比，平均基线变化差异为-2-5 [95% CI -4-5 to -0-6]；治疗差异为3-1 [95% CI 0-2 to 6-0]）。卡匹伐他汀-氟维司群组的 EORTC QLQ-C30 GHS/QOL 中位恶化时间为 24-9 个月（95% CI 13-8 至未达到），安慰剂-氟维司群组为 12-0 个月（10-2 至 15-7）（危险比 [HR] 0-70，95% CI 0-53 至 0-92）。所有EORTC QLQ-C30和QLQ-BR23分量表评分的恶化时间HR在治疗组之间差异不大，但腹泻除外，卡匹伐他汀-氟维司群组的腹泻症状比安慰剂-氟维司群组更严重（HR 2-75，95% CI 2-01-3-81）。在PRO-CTCAE症状评估中，报告 "经常 "或 "几乎经常 "出现稀便和水样便的患者比例在第1周期第15天时，卡匹伐他汀-氟维司群组比安慰剂-氟维司群组高29%，在随后的周期中有所下降。
{"title":"Capivasertib and fulvestrant for patients with hormone receptor-positive, HER2-negative advanced breast cancer (CAPItello-291): patient-reported outcomes from a phase 3, randomised, double-blind, placebo-controlled trial.","authors":"Mafalda Oliveira, Hope S Rugo, Sacha J Howell, Florence Dalenc, Javier Cortes, Henry L Gomez, Xichun Hu, Masakazu Toi, Komal Jhaveri, Petr Krivorotko, Sibylle Loibl, Serafin Morales Murillo, Meena Okera, Zbigniew Nowecki, Yeon Hee Park, Joo Hyuk Sohn, Eriko Tokunaga, Samih Yousef, Lyudmila Zhukova, Marta Fulford, Haylee Andrews, Ian Wadsworth, Celina D'Cruz, Nicholas C Turner","doi":"10.1016/S1470-2045(24)00373-5","DOIUrl":"10.1016/S1470-2045(24)00373-5","url":null,"abstract":"<p><strong>Background: </strong>CAPItello-291 is an ongoing phase 3 trial in which capivasertib-fulvestrant significantly improved progression-free survival versus placebo-fulvestrant in patients with hormone receptor-positive, HER2-negative advanced breast cancer who had relapse or disease progression during or after aromatase inhibitor treatment, in both the overall population and in patients with PIK3CA, AKT1, or PTEN-altered tumours. This study further explored patient-reported health-related quality of life (HRQOL), functioning, symptoms, and symptom tolerability in CAPItello-291.</p><p><strong>Methods: </strong>This phase 3, randomised, double-blind, placebo-controlled trial, which was conducted across 193 hospitals and cancer centres in 19 countries, enrolled women with any menopausal status or men, aged ≥18 years (≥20 years in Japan), with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer who had relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase (CDK) 4 or 6 inhibitor therapy. Patients had an Eastern Cooperative Oncology Group/WHO performance score of 0 or 1 and could have received up to two previous lines of endocrine therapy and up to one previous line of chemotherapy for advanced disease. Patients were randomly assigned (1:1) using block randomisation (stratified according to the presence or absence of liver metastases, previous use of a CDK4/6 inhibitor [yes vs no], and geographical region) to receive oral capivasertib 400 mg (twice daily for 4 days, followed by 3 days off) plus intramuscular fulvestrant 500 mg (every 14 days for the first three injections, then every 28 days) or placebo with matching fulvestrant dosing. The dual primary endpoint of the trial was investigator-assessed progression-free survival assessed both in the overall population and among patients with PIK3CA, AKT1, or PTEN-altered tumours. The EORTC Quality of Life Questionnaire 30-item core module (QLQ-C30) and breast module (QLQ-BR23), Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and Patient Global Impression of Treatment Tolerability (PGI-TT) questionnaires were used to assess patient-reported outcomes. Evaluation of EORTC QLQ-C30 and EORTC QLQ-BR23 were secondary endpoints and evaluation of PRO-CTCAE and PGI-TT were pre-defined exploratory endpoints, and these endpoints are the subject of analysis in this Article. Data were collected at baseline and prespecified timepoints. Patient-reported outcomes were analysed in all randomly assigned patients with an evaluable baseline assessment and at least one evaluable post-baseline assessment. Change from baseline was assessed using mixed model with repeated measures for EORTC QLQ-C30 and summarised for QLQ-BR23. Time to deterioration was described using the Kaplan-Meier method. PGI-TT and PRO-CTCAE responses were summarised at each treatment ","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":"25 9","pages":"1231-1244"},"PeriodicalIF":41.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/S1470-2045(24)00390-5
Ghada Zakout
{"title":"Contextualising legal and ethical conundrums of artificial intelligence in oncology.","authors":"Ghada Zakout","doi":"10.1016/S1470-2045(24)00390-5","DOIUrl":"https://doi.org/10.1016/S1470-2045(24)00390-5","url":null,"abstract":"","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":"25 9","pages":"1113-1116"},"PeriodicalIF":41.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-07DOI: 10.1016/S1470-2045(24)00318-8
Jean-Yves Blay, Quentin Devin, Florence Duffaud, Maud Toulmonde, Nelly Firmin, Olivier Collard, Emmanuelle Bompas, Benjamin Verret, Isabelle Ray-Coquard, Sebastien Salas, Clemence Henon, Charles Honoré, Mehdi Brahmi, Armelle Dufresne, Marc Pracht, Alice Hervieu, Nicolas Penel, Francois Bertucci, Maria Rios, Esma Saada-Bouzid, Pauline Soibinet, David Perol, Sylvie Chabaud, Antoine Italiano, Axel Le Cesne
<p><strong>Background: </strong>The long-term impact of tyrosine kinase inhibitor (TKI) discontinuation on resistance and survival in patients with advanced gastrointestinal stromal tumours (GIST) is unclear. We report the exploratory long-term outcomes of patients with advanced GIST stopping imatinib in the BFR14 trial.</p><p><strong>Methods: </strong>BFR14, an open-label, randomised, phase 3 trial, was done in 17 comprehensive cancer centres or hospitals across France. Patients with advanced GIST aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-3, no previous treatment with imatinib, and no previous malignancy were eligible. Patients were treated with oral imatinib 400 mg daily. Patients with a complete or partial response, or stable disease, according to Response Evaluation Criteria in Solid Tumours (1.0) at 1 year, 3 years, and 5 years from the start of treatment were randomly assigned (1:1) to treatment discontinuation until progression (interruption group) or treatment continuation until progression (continuation group). Randomisation was done centrally with computer-generated permuted blocks of two and six patients stratified by participating centre and presence or absence of residual disease on CT scan. The primary endpoint was progression-free survival. Secondary endpoints included time to imatinib resistance and overall survival. Analyses were conducted on an intention-to-treat basis in all randomly assigned patients who were not lost to follow-up. This trial is registered with ClinicalTrial.gov, NCT00367861.</p><p><strong>Findings: </strong>Between May 12, 2003, and March 16, 2004, after 1 year of imatinib, 32 patients were randomly assigned to the interruption group and 26 to the continuation group. Between June 13, 2005, and May 30, 2007, after 3 years of imatinib, 25 patients were randomly assigned to the interruption group and 25 to the continuation group. Between Nov 9, 2007, and July 12, 2010, after 5 years of imatinib, 14 patients were randomly assigned to the interruption group and 13 to the continuation group. Median follow-up was 235·2 months (IQR 128·8-236·6) after the 1-year randomisation, 200·9 months (190·2-208·4) after the 3-year randomisation, and 164·5 months (134·4-176·4) after the 5-year randomisation. Median progression-free survival in the interruption group versus the continuation group after 1 year of imatinib was 6·1 months (95% CI 2·5-10·1) versus 27·8 months (19·5-37·9; hazard ratio [HR] 0·36 [95% CI 0·20-0·64], log-rank p=0·0003), after 3 years of imatinib was 7·0 months (3·5-11·7) versus 67·0 months (48·8-85·6; 0·15 [0·07-0·32], log-rank p<0·0001), and after 5 years of imatinib was 12·0 months (9·0-16·6) versus not reached (NR; NR-NR; 0·13 [0·03-0·58], log-rank p=0·0016). The median time to imatinib resistance after 1 year of imatinib was 28·7 months (95% CI 18·1-39·1) versus 90·6 months (25·3-156·1; HR 0·93 [95% CI 0·51-1·71], log-rank p=0·82), after 3 years was 66·2
背景：酪氨酸激酶抑制剂（TKI）停药对晚期胃肠道间质瘤（GIST）患者耐药性和生存期的长期影响尚不明确。我们报告了在BFR14试验中停用伊马替尼的晚期GIST患者的探索性长期疗效：BFR14是一项开放标签、随机3期试验，在法国17家综合癌症中心或医院进行。年龄在18岁或18岁以上的晚期GIST患者符合条件：东部合作肿瘤学组（Eastern Cooperative Oncology Group）表现为0-3级，既往未接受过伊马替尼治疗，既往未患恶性肿瘤。患者每天口服伊马替尼 400 毫克。根据《实体瘤反应评估标准》（1.0），在治疗开始后1年、3年和5年时获得完全或部分反应或病情稳定的患者将被随机分配（1:1）至中断治疗直至病情进展（中断组）或继续治疗直至病情进展（继续组）。随机分配由计算机集中生成，按参与中心和CT扫描有无残留疾病对2至6名患者进行分层。主要终点是无进展生存期。次要终点包括伊马替尼耐药时间和总生存期。在意向治疗的基础上，对所有未失去随访机会的随机分配患者进行了分析。该试验已在ClinicalTrial.gov网站注册，编号为NCT00367861：2003年5月12日至2004年3月16日，伊马替尼治疗一年后，32名患者被随机分配到中断治疗组，26名患者被随机分配到继续治疗组。2005年6月13日至2007年5月30日，伊马替尼治疗3年后，25名患者被随机分配到中断治疗组，25名患者被随机分配到继续治疗组。2007年11月9日至2010年7月12日，伊马替尼治疗5年后，14名患者被随机分配到中断治疗组，13名患者被随机分配到继续治疗组。随机分配1年后的中位随访时间为235-2个月（IQR 128-8-236-6），随机分配3年后的中位随访时间为200-9个月（190-2-208-4），随机分配5年后的中位随访时间为164-5个月（134-4-176-4）。服用伊马替尼1年后，中断组与继续服用组的中位无进展生存期分别为6-1个月（95% CI 2-5-10-1）对27-8个月（19-5-37-9；危险比[HR] 0-36[95% CI 0-20-0-64]，对数rank p=0-0003）；服用伊马替尼3年后，中断组与继续服用组的中位无进展生存期分别为7-0个月（3-5-11-7）对67-0个月（48-8-85-6；0-15[0-07-0-32]，对数rank pFunding：Centre Léon Bérard、INCa、CONTICANET、Ligue Contre le Cancer 和 Novartis。
{"title":"Discontinuation versus continuation of imatinib in patients with advanced gastrointestinal stromal tumours (BFR14): exploratory long-term follow-up of an open-label, multicentre, randomised, phase 3 trial.","authors":"Jean-Yves Blay, Quentin Devin, Florence Duffaud, Maud Toulmonde, Nelly Firmin, Olivier Collard, Emmanuelle Bompas, Benjamin Verret, Isabelle Ray-Coquard, Sebastien Salas, Clemence Henon, Charles Honoré, Mehdi Brahmi, Armelle Dufresne, Marc Pracht, Alice Hervieu, Nicolas Penel, Francois Bertucci, Maria Rios, Esma Saada-Bouzid, Pauline Soibinet, David Perol, Sylvie Chabaud, Antoine Italiano, Axel Le Cesne","doi":"10.1016/S1470-2045(24)00318-8","DOIUrl":"10.1016/S1470-2045(24)00318-8","url":null,"abstract":"<p><strong>Background: </strong>The long-term impact of tyrosine kinase inhibitor (TKI) discontinuation on resistance and survival in patients with advanced gastrointestinal stromal tumours (GIST) is unclear. We report the exploratory long-term outcomes of patients with advanced GIST stopping imatinib in the BFR14 trial.</p><p><strong>Methods: </strong>BFR14, an open-label, randomised, phase 3 trial, was done in 17 comprehensive cancer centres or hospitals across France. Patients with advanced GIST aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-3, no previous treatment with imatinib, and no previous malignancy were eligible. Patients were treated with oral imatinib 400 mg daily. Patients with a complete or partial response, or stable disease, according to Response Evaluation Criteria in Solid Tumours (1.0) at 1 year, 3 years, and 5 years from the start of treatment were randomly assigned (1:1) to treatment discontinuation until progression (interruption group) or treatment continuation until progression (continuation group). Randomisation was done centrally with computer-generated permuted blocks of two and six patients stratified by participating centre and presence or absence of residual disease on CT scan. The primary endpoint was progression-free survival. Secondary endpoints included time to imatinib resistance and overall survival. Analyses were conducted on an intention-to-treat basis in all randomly assigned patients who were not lost to follow-up. This trial is registered with ClinicalTrial.gov, NCT00367861.</p><p><strong>Findings: </strong>Between May 12, 2003, and March 16, 2004, after 1 year of imatinib, 32 patients were randomly assigned to the interruption group and 26 to the continuation group. Between June 13, 2005, and May 30, 2007, after 3 years of imatinib, 25 patients were randomly assigned to the interruption group and 25 to the continuation group. Between Nov 9, 2007, and July 12, 2010, after 5 years of imatinib, 14 patients were randomly assigned to the interruption group and 13 to the continuation group. Median follow-up was 235·2 months (IQR 128·8-236·6) after the 1-year randomisation, 200·9 months (190·2-208·4) after the 3-year randomisation, and 164·5 months (134·4-176·4) after the 5-year randomisation. Median progression-free survival in the interruption group versus the continuation group after 1 year of imatinib was 6·1 months (95% CI 2·5-10·1) versus 27·8 months (19·5-37·9; hazard ratio [HR] 0·36 [95% CI 0·20-0·64], log-rank p=0·0003), after 3 years of imatinib was 7·0 months (3·5-11·7) versus 67·0 months (48·8-85·6; 0·15 [0·07-0·32], log-rank p<0·0001), and after 5 years of imatinib was 12·0 months (9·0-16·6) versus not reached (NR; NR-NR; 0·13 [0·03-0·58], log-rank p=0·0016). The median time to imatinib resistance after 1 year of imatinib was 28·7 months (95% CI 18·1-39·1) versus 90·6 months (25·3-156·1; HR 0·93 [95% CI 0·51-1·71], log-rank p=0·82), after 3 years was 66·2","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":" ","pages":"1163-1175"},"PeriodicalIF":41.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-06DOI: 10.1016/S1470-2045(24)00385-1
Andrea V Barrio
{"title":"Time to abandon axillary lymph node dissection in early-stage breast cancer.","authors":"Andrea V Barrio","doi":"10.1016/S1470-2045(24)00385-1","DOIUrl":"10.1016/S1470-2045(24)00385-1","url":null,"abstract":"","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":" ","pages":"1111-1113"},"PeriodicalIF":41.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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