Pub Date : 2026-02-01Epub Date: 2026-01-07DOI: 10.1016/S1470-2045(25)00653-9
Hermann Einsele, Jesús San-Miguel, Binod Dhakal, Cyrille Touzeau, Xavier Leleu, Niels Wcj van de Donk, Surbhi Sidana, Albert Oriol, Yael C Cohen, Simon J Harrison, María-Victoria Mateos, Joaquín Martínez-López, Paolo Corradini, Lionel Karlin, Diana Chen, Quanlin Li, Tzu-Min Yeh, Katherine Li, Vicki Plaks, Ana Slaughter, Carolina Lonardi, Nina Benachour, Arnab Ghosh, Martin Vogel, Jordan M Schecter, Nikoletta Lendvai, Mythili Koneru, Nitin Patel, Erika Florendo, Phoebe Joy Ho, Rakesh Popat
<p><strong>Background: </strong>In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes.</p><p><strong>Methods: </strong>CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 10<sup>6</sup> CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m<sup>2</sup> subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing.</p><p><strong>Findings: </strong>Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-n
{"title":"Cilta-cel in lenalidomide-refractory multiple myeloma (CARTITUDE-4): an updated analysis including overall survival from an open-label, multicentre, randomised, phase 3 trial.","authors":"Hermann Einsele, Jesús San-Miguel, Binod Dhakal, Cyrille Touzeau, Xavier Leleu, Niels Wcj van de Donk, Surbhi Sidana, Albert Oriol, Yael C Cohen, Simon J Harrison, María-Victoria Mateos, Joaquín Martínez-López, Paolo Corradini, Lionel Karlin, Diana Chen, Quanlin Li, Tzu-Min Yeh, Katherine Li, Vicki Plaks, Ana Slaughter, Carolina Lonardi, Nina Benachour, Arnab Ghosh, Martin Vogel, Jordan M Schecter, Nikoletta Lendvai, Mythili Koneru, Nitin Patel, Erika Florendo, Phoebe Joy Ho, Rakesh Popat","doi":"10.1016/S1470-2045(25)00653-9","DOIUrl":"10.1016/S1470-2045(25)00653-9","url":null,"abstract":"<p><strong>Background: </strong>In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes.</p><p><strong>Methods: </strong>CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 10<sup>6</sup> CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m<sup>2</sup> subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing.</p><p><strong>Findings: </strong>Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-n","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":" ","pages":"254-268"},"PeriodicalIF":35.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948468","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 : 2024-11-01Epub Date: 2024-08-28DOI: 10.1016/S1470-2045(24)00262-6
Philippe Morice, Giovanni Scambia, Nadeem R Abu-Rustum, Maribel Acien, Alessandro Arena, Sara Brucker, Ying Cheong, Pierre Collinet, Francesco Fanfani, Francesca Filippi, Ane Gerda Zahl Eriksson, Sebastien Gouy, Philipp Harter, Xavier Matias-Guiu, George Pados, Maja Pakiz, Denis Querleu, Alexandros Rodolakis, Christine Rousset-Jablonski, Artem Stepanyan, Antonia Carla Testa, Kirsten Tryde Macklon, Dimitrios Tsolakidis, Michel De Vos, François Planchamp, Michaël Grynberg
The European Society of Gynaecological Oncology, the European Society of Human Reproduction and Embryology, and the European Society for Gynaecological Endoscopy jointly developed clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing strategies and follow-up of patients with cervical cancers, ovarian cancers, and borderline ovarian tumours. The developmental process of these guidelines is based on a systematic literature review and critical appraisal involving an international multidisciplinary development group consisting of 25 experts from relevant disciplines (ie, gynaecological oncology, oncofertility, reproductive surgery, endoscopy, imaging, conservative surgery, medical oncology, and histopathology). Before publication, the guidelines were reviewed by 121 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover oncological aspects of fertility-sparing strategies during the initial management, optimisation of fertility results and infertility management, and the patient's desire for future pregnancy and beyond.
{"title":"Fertility-sparing treatment and follow-up in patients with cervical cancer, ovarian cancer, and borderline ovarian tumours: guidelines from ESGO, ESHRE, and ESGE.","authors":"Philippe Morice, Giovanni Scambia, Nadeem R Abu-Rustum, Maribel Acien, Alessandro Arena, Sara Brucker, Ying Cheong, Pierre Collinet, Francesco Fanfani, Francesca Filippi, Ane Gerda Zahl Eriksson, Sebastien Gouy, Philipp Harter, Xavier Matias-Guiu, George Pados, Maja Pakiz, Denis Querleu, Alexandros Rodolakis, Christine Rousset-Jablonski, Artem Stepanyan, Antonia Carla Testa, Kirsten Tryde Macklon, Dimitrios Tsolakidis, Michel De Vos, François Planchamp, Michaël Grynberg","doi":"10.1016/S1470-2045(24)00262-6","DOIUrl":"10.1016/S1470-2045(24)00262-6","url":null,"abstract":"<p><p>The European Society of Gynaecological Oncology, the European Society of Human Reproduction and Embryology, and the European Society for Gynaecological Endoscopy jointly developed clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing strategies and follow-up of patients with cervical cancers, ovarian cancers, and borderline ovarian tumours. The developmental process of these guidelines is based on a systematic literature review and critical appraisal involving an international multidisciplinary development group consisting of 25 experts from relevant disciplines (ie, gynaecological oncology, oncofertility, reproductive surgery, endoscopy, imaging, conservative surgery, medical oncology, and histopathology). Before publication, the guidelines were reviewed by 121 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover oncological aspects of fertility-sparing strategies during the initial management, optimisation of fertility results and infertility management, and the patient's desire for future pregnancy and beyond.</p>","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":" ","pages":"e602-e610"},"PeriodicalIF":35.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108837","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 : 2024-11-01Epub Date: 2024-09-26DOI: 10.1016/S1470-2045(24)00533-3
Emma Wilkinson
{"title":"Organisations withdraw from cancer conference over tobacco link.","authors":"Emma Wilkinson","doi":"10.1016/S1470-2045(24)00533-3","DOIUrl":"10.1016/S1470-2045(24)00533-3","url":null,"abstract":"","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":" ","pages":"1400"},"PeriodicalIF":41.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349296","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 : 2024-11-01Epub Date: 2024-09-27DOI: 10.1016/S1470-2045(24)00535-7
Tony Kirby
{"title":"AACR highlights advances and threats to US cancer research.","authors":"Tony Kirby","doi":"10.1016/S1470-2045(24)00535-7","DOIUrl":"10.1016/S1470-2045(24)00535-7","url":null,"abstract":"","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":" ","pages":"1402"},"PeriodicalIF":41.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349295","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 : 2024-10-01Epub Date: 2024-09-13DOI: 10.1016/S1470-2045(24)00389-9
Othon Iliopoulos, Ane B Iversen, Vivek Narayan, Benjamin L Maughan, Kathryn E Beckermann, Stephane Oudard, Tobias Else, Jodi K Maranchie, Cynthia Muller Goldberg, Wei Fu, Rodolfo F Perini, Yanfang Liu, W Marston Linehan, Ramaprasad Srinivasan, Eric Jonasch
<p><strong>Background: </strong>The first-in-class hypoxia-inducible factor-2α inhibitor, belzutifan, showed clinically meaningful antitumour activity in von Hippel-Lindau (VHL) disease-associated neoplasms in the ongoing, single-arm, phase 2 LITESPARK-004 study. We aimed to investigate antitumour activity with an additional 16 months of follow-up and present updated results for the subgroup of patients with CNS haemangioblastomas.</p><p><strong>Methods: </strong>In the multicentre, single-arm, phase 2 LITESPARK-004 study, adults (aged ≥18 years) from 11 cancer centres or hospitals in the USA, Denmark, France, and the UK, with germline VHL alterations, at least one measurable renal cell carcinoma tumour, no renal cell carcinoma tumour greater than 3 cm requiring immediate surgical intervention, an Eastern Cooperative Oncology Group performance status 0 or 1, and no previous systemic therapy received oral belzutifan 120 mg once daily until unacceptable toxicity, disease progression, or patient decision to withdraw. The primary endpoint, evaluated in patients with CNS haemangioblastomas, was the proportion of patients with an objective response per RECIST version 1.1 by an independent review committee. We assessed response using two approaches. In approach 1, we evaluated all measurable (≥1 cm maximum diameter) or non-measurable lesions at baseline, including both the solid lesion and the associated cystic component if present. In approach 2, we evaluated only baseline lesions with a measurable (≥1 cm maximum diameter) solid lesion. Antitumour activity was assessed in all patients who received at least one dose of belzutifan. This study is no longer recruiting but is ongoing, and is registered with Clinicaltrials.gov, NCT03401788.</p><p><strong>Findings: </strong>Between May 31, 2018, and March 29, 2019, of 67 patients screened, 61 (32 [52%] male and 29 [48%] female) were enrolled; 50 (82%) had at least one CNS haemangioblastoma evaluable at baseline (184 total lesions). Median follow-up for the 50 patients with CNS haemangioblastomas was 38·0 months (IQR 36·7-40·1). In approach 1, 22 of 50 patients (44% [95% CI 30-59]) had an objective response. In approach 2, 19 of 25 patients (76% [55-91] had an objective response. 23 (46%) of 50 patients had a grade 3-5 all-cause adverse event. 19 (38%) patients reported grade 3 adverse events, the most common of which was anaemia (in 6 [12%] patients). Two of 50 patients (4%) reported grade 4 events (retinal vein occlusion and embolism). Two patients died owing to adverse events not considered treatment-related (suicide and toxicity to various agents).</p><p><strong>Interpretation: </strong>Belzutifan showed meaningful antitumour activity in VHL disease-associated CNS haemangioblastomas that was sustained for more than 3 years of treatment. These results continue to support belzutifan as a systemic treatment option for patients with VHL disease-related CNS haemangioblastomas.</p><p><strong>Funding: </strong>Me
{"title":"Belzutifan for patients with von Hippel-Lindau disease-associated CNS haemangioblastomas (LITESPARK-004): a multicentre, single-arm, phase 2 study.","authors":"Othon Iliopoulos, Ane B Iversen, Vivek Narayan, Benjamin L Maughan, Kathryn E Beckermann, Stephane Oudard, Tobias Else, Jodi K Maranchie, Cynthia Muller Goldberg, Wei Fu, Rodolfo F Perini, Yanfang Liu, W Marston Linehan, Ramaprasad Srinivasan, Eric Jonasch","doi":"10.1016/S1470-2045(24)00389-9","DOIUrl":"10.1016/S1470-2045(24)00389-9","url":null,"abstract":"<p><strong>Background: </strong>The first-in-class hypoxia-inducible factor-2α inhibitor, belzutifan, showed clinically meaningful antitumour activity in von Hippel-Lindau (VHL) disease-associated neoplasms in the ongoing, single-arm, phase 2 LITESPARK-004 study. We aimed to investigate antitumour activity with an additional 16 months of follow-up and present updated results for the subgroup of patients with CNS haemangioblastomas.</p><p><strong>Methods: </strong>In the multicentre, single-arm, phase 2 LITESPARK-004 study, adults (aged ≥18 years) from 11 cancer centres or hospitals in the USA, Denmark, France, and the UK, with germline VHL alterations, at least one measurable renal cell carcinoma tumour, no renal cell carcinoma tumour greater than 3 cm requiring immediate surgical intervention, an Eastern Cooperative Oncology Group performance status 0 or 1, and no previous systemic therapy received oral belzutifan 120 mg once daily until unacceptable toxicity, disease progression, or patient decision to withdraw. The primary endpoint, evaluated in patients with CNS haemangioblastomas, was the proportion of patients with an objective response per RECIST version 1.1 by an independent review committee. We assessed response using two approaches. In approach 1, we evaluated all measurable (≥1 cm maximum diameter) or non-measurable lesions at baseline, including both the solid lesion and the associated cystic component if present. In approach 2, we evaluated only baseline lesions with a measurable (≥1 cm maximum diameter) solid lesion. Antitumour activity was assessed in all patients who received at least one dose of belzutifan. This study is no longer recruiting but is ongoing, and is registered with Clinicaltrials.gov, NCT03401788.</p><p><strong>Findings: </strong>Between May 31, 2018, and March 29, 2019, of 67 patients screened, 61 (32 [52%] male and 29 [48%] female) were enrolled; 50 (82%) had at least one CNS haemangioblastoma evaluable at baseline (184 total lesions). Median follow-up for the 50 patients with CNS haemangioblastomas was 38·0 months (IQR 36·7-40·1). In approach 1, 22 of 50 patients (44% [95% CI 30-59]) had an objective response. In approach 2, 19 of 25 patients (76% [55-91] had an objective response. 23 (46%) of 50 patients had a grade 3-5 all-cause adverse event. 19 (38%) patients reported grade 3 adverse events, the most common of which was anaemia (in 6 [12%] patients). Two of 50 patients (4%) reported grade 4 events (retinal vein occlusion and embolism). Two patients died owing to adverse events not considered treatment-related (suicide and toxicity to various agents).</p><p><strong>Interpretation: </strong>Belzutifan showed meaningful antitumour activity in VHL disease-associated CNS haemangioblastomas that was sustained for more than 3 years of treatment. These results continue to support belzutifan as a systemic treatment option for patients with VHL disease-related CNS haemangioblastomas.</p><p><strong>Funding: </strong>Me","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":" ","pages":"1325-1336"},"PeriodicalIF":35.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-08-30DOI: 10.1016/S1470-2045(24)00324-3
Elizabeth Gourd
{"title":"World's first lung cancer vaccine trial launched in the UK.","authors":"Elizabeth Gourd","doi":"10.1016/S1470-2045(24)00324-3","DOIUrl":"10.1016/S1470-2045(24)00324-3","url":null,"abstract":"","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":" ","pages":"1258"},"PeriodicalIF":35.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120169","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 : 2024-10-01Epub Date: 2024-08-20DOI: 10.1016/S1470-2045(24)00448-0
Mark Lawler, Ajay Aggarwal, Julie Gralow, Richard Sullivan, Pat Price
{"title":"The UK needs to be a leader, not a lagger, in the global cancer effort.","authors":"Mark Lawler, Ajay Aggarwal, Julie Gralow, Richard Sullivan, Pat Price","doi":"10.1016/S1470-2045(24)00448-0","DOIUrl":"10.1016/S1470-2045(24)00448-0","url":null,"abstract":"","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":" ","pages":"1253-1254"},"PeriodicalIF":35.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046857","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 : 2024-10-01Epub Date: 2024-09-11DOI: 10.1016/S1470-2045(24)00437-6
Zikun Peng, Huayi Li, Yunong Gao, Li Sun, Jie Jiang, Bairong Xia, Yi Huang, Yu Zhang, Yu Xia, Yuxin Zhang, Yiyang Shen, Bowen Huang, Jiayu Nie, Xinrong Chen, Xingyu Liu, Cui Feng, Zhen Li, Wei Zhang, Kangjia Tao, Qiuxue Zhang, Shican Duan, Yaheng Chen, Yeshan Chen, Wei Wang, Hong Zheng, Yudong Lu, Yi Liu, Limei Wang, Wencai Qi, Yang He, Yan Tian, Guiling Li, Ding Ma, Qinglei Gao
<p><strong>Background: </strong>Ovarian clear cell carcinoma rarely responds to second-line chemotherapy, the recommended treatment for relapsed epithelial ovarian cancer. Here, we report the activity and safety of sintilimab in combination with bevacizumab in patients with relapsed or persistent ovarian clear cell carcinoma.</p><p><strong>Methods: </strong>In the prospective, multicentre, single-arm, phase 2 INOVA trial, patients aged 18-75 years with histologically confirmed relapsed or persistent ovarian clear cell carcinoma were enrolled from eight tertiary hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group performance status score of 0-2 and previous exposure to at least one cycle of platinum-containing chemotherapy. Enrolled patients received sintilimab (200 mg) and bevacizumab (15 mg/kg) intravenously every 3 weeks until disease progression. The primary endpoint was objective response rate assessed by independent central review based on Response Evaluation Criteria in Solid Tumours version 1.1. Eligible enrolled patients who received at least one cycle of treatment and had at least one tumour response assessment following the baseline assessment per protocol were included in the activity analysis. Patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04735861) and is ongoing.</p><p><strong>Findings: </strong>Between April 8, 2021, and July 3, 2023, 51 patients were screened and 41 patients received at least one dose of sintilimab in combination with bevacizumab. Response evaluation was completed in 37 patients. Objective responses were observed in 15 patients (objective response rate 40·5%; 95% CI 24·8-57·9), of which five (14%) were complete responses and ten (27%) were partial responses. At data cutoff (Jan 29, 2024), the median follow-up was 16·9 months (IQR 7·5-23·4). Three (7%) patients developed grade 3 treatment-related adverse events including one patient with proteinuria, one patient with myocarditis, and one patient with rash. No treatment-related adverse events of worse than grade 3 severity were recorded. Treatment-related serious adverse events occurred in two (5%) patients including one patient with immune-related myocarditis and another with hypertension and renal dysfunction. No treatment-related deaths occurred.</p><p><strong>Interpretation: </strong>Sintilimab in combination with bevacizumab showed promising anti-tumour activity and manageable safety in patients with relapsed or persistent ovarian clear cell carcinoma. Larger, randomised trials are warranted to compare this low-toxicity, chemotherapy-free combinatorial regimen with standard chemotherapy.</p><p><strong>Funding: </strong>National Key Technology Research and Development Program of China, National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Innovent Biologics.</p><p><strong>Translation: </str
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