Pub Date : 2024-11-14DOI: 10.1016/s1470-2045(24)00586-2
Kerry L Reynolds, Pauline Funchain
No Abstract
无摘要
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Pub Date : 2024-11-14DOI: 10.1016/s1470-2045(24)00507-2
Loren K Mell, Pedro A Torres-Saavedra, Stuart J Wong, Julie A Kish, Steven S Chang, Richard C Jordan, Tian Liu, Minh Tam Truong, Eric W Winquist, Vinita Takiar, Trisha Wise-Draper, Jared R Robbins, Cristina P Rodriguez, Musaddiq J Awan, Beth M Beadle, Christina Henson, Samir Narayan, Sharon A Spencer, Steven Powell, Neal Dunlap, Quynh-Thu Le
<h3>Background</h3>Management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) when cisplatin is contraindicated is controversial. We aimed to assess whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab.<h3>Methods</h3>NRG-HN004 was designed as an open-label, multicentre, parallel-group, randomised, phase 2/3 trial with safety lead-in conducted at 89 academic and community medical centres in North America. Eligible patients were aged 18 years or older with American Joint Committee on Cancer 8th edition stage III–IVB p16-negative HNSCC or unfavourable stage I–III p16-positive oropharyngeal or unknown primary carcinoma, who had a contraindication to cisplatin (Eastern Cooperative Oncology Group [ECOG] performance status 2, renal or hearing impairment, peripheral neuropathy, aged at least 70 years with moderate or severe comorbidity, or aged younger than 70 years with severe comorbidity). Patients were randomly assigned (2:1) by permuted block randomisation (multiples of 6) to intravenous durvalumab 1500 mg starting 2 weeks before radiotherapy then every 4 weeks starting week 2 of radiotherapy (seven cycles) or intravenous cetuximab 400 mg/m<sup>2</sup> 1 week before radiotherapy then 250 mg/m<sup>2</sup> weekly beginning week 1 of radiotherapy (eight cycles), with intensity-modulated radiotherapy (70 Gy in 35 fractions over 7 weeks). Stratification factors were tumour and nodal stage, ECOG performance status and comorbidity, and primary site and p16 status. The phase 2 primary endpoint was progression-free survival in the intention-to-treat population. There was one prespecified interim futility analysis at 50% of progression-free survival information. If the observed hazard ratio was 1·0 or more, favouring cetuximab, early stopping would be considered. Extended follow-up analysis was post hoc. This trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, <span><span>NCT03258554</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, and is closed to enrolment.<h3>Findings</h3>Following a ten-patient safety lead-in, the phase 2 trial enrolled 190 patients from March 12, 2019, to July 30, 2021, 186 of whom were randomly assigned (123 to durvalumab and 63 to cetuximab). Median age was 72 years (IQR 64–77), 30 (16%) patients were women and 156 (84%) were men. Phase 2 accrual was suspended in July 30, 2021, following an interim futility analysis, and permanently closed in Sept 1, 2022. The phase 3 part of the trial was not conducted. At a median follow-up of 2·3 years (IQR 1·9–3·1)
背景在顺铂禁忌症的情况下，局部区域晚期头颈部鳞状细胞癌（HNSCC）患者的治疗存在争议。方法NRG-HN004是一项开放标签、多中心、平行组、随机、2/3期试验，在北美的89个学术和社区医疗中心进行。符合条件的患者年龄在18岁或18岁以上，患有美国癌症联合委员会第8版III-IVB期p16阴性HNSCC或I-III期p16阳性口咽癌或不明原发癌，且有顺铂禁忌症（东部合作肿瘤学组[ECOG]表现状态2、肾功能或听力受损、周围神经病变、年龄至少70岁且有中度或重度合并症，或年龄小于70岁且有重度合并症）。患者通过包块随机化（6的倍数）被随机分配（2:1）至静脉注射杜瓦鲁单抗1500毫克（放疗前2周开始）或静脉注射西妥昔单抗400毫克/平方米（放疗前1周开始）或静脉注射西妥昔单抗250毫克/平方米（放疗前1周开始），然后从放疗第1周开始每周注射250毫克/平方米（8个周期），同时接受调强放疗（70 Gy，35次/分，7周）。分层因素包括肿瘤和结节分期、ECOG表现状态和合并症、原发部位和p16状态。二期研究的主要终点是意向治疗人群的无进展生存期。在无进展生存期信息为50%时进行了一次预设的中期无用性分析。如果观察到的危险比为1-0或更高，且西妥昔单抗更有利，则将考虑提前停止治疗。延长随访分析为事后分析。该试验已在ClinicalTrials.gov注册，编号为NCT03258554，目前已结束报名。研究结果在10名患者的安全先导试验后，2期试验从2019年3月12日到2021年7月30日共招募了190名患者，其中186名患者被随机分配（123名患者接受度伐单抗治疗，63名患者接受西妥昔单抗治疗）。中位年龄为72岁（IQR 64-77），30名（16%）患者为女性，156名（84%）患者为男性。在进行中期无效性分析后，2期试验于2021年7月30日暂停，并于2022年9月1日永久结束。该试验的 3 期部分没有进行。在中位随访2-3年（IQR 1-9-3-1）的延长随访中（数据截止日期为2023年7月31日；事后分析），durvalumab组的2年无进展生存率为50-6%（95% CI 41-5-59-8），而西妥昔单抗组为63-7%（51-3-76-1）（危险比1-33 [95% CI 0-84-2-12]；P=0-89）。两组的不良事件相似。最常见的3-4级不良事件是吞咽困难（119例杜瓦单抗组患者中26例[22%] vs 61例西妥昔单抗组患者中18例[30%]）、淋巴细胞减少症（33例[28%] vs 20例[33%]）和口腔黏膜炎（13例[11%] vs 11例[18%]）。杜瓦鲁单抗组和西妥昔单抗组分别有4名（3%）和1名（2%）患者死于与治疗相关的不良事件（杜瓦鲁单抗组患者死于未注明原因的死亡、喉头水肿、肺部感染和呼吸衰竭，西妥昔单抗组患者死于未注明原因的猝死）。需要进一步的试验来确定这一人群的治疗标准。资金来源美国国家癌症研究所和阿斯利康公司。
{"title":"Radiotherapy with cetuximab or durvalumab for locoregionally advanced head and neck cancer in patients with a contraindication to cisplatin (NRG-HN004): an open-label, multicentre, parallel-group, randomised, phase 2/3 trial","authors":"Loren K Mell, Pedro A Torres-Saavedra, Stuart J Wong, Julie A Kish, Steven S Chang, Richard C Jordan, Tian Liu, Minh Tam Truong, Eric W Winquist, Vinita Takiar, Trisha Wise-Draper, Jared R Robbins, Cristina P Rodriguez, Musaddiq J Awan, Beth M Beadle, Christina Henson, Samir Narayan, Sharon A Spencer, Steven Powell, Neal Dunlap, Quynh-Thu Le","doi":"10.1016/s1470-2045(24)00507-2","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00507-2","url":null,"abstract":"<h3>Background</h3>Management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) when cisplatin is contraindicated is controversial. We aimed to assess whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab.<h3>Methods</h3>NRG-HN004 was designed as an open-label, multicentre, parallel-group, randomised, phase 2/3 trial with safety lead-in conducted at 89 academic and community medical centres in North America. Eligible patients were aged 18 years or older with American Joint Committee on Cancer 8th edition stage III–IVB p16-negative HNSCC or unfavourable stage I–III p16-positive oropharyngeal or unknown primary carcinoma, who had a contraindication to cisplatin (Eastern Cooperative Oncology Group [ECOG] performance status 2, renal or hearing impairment, peripheral neuropathy, aged at least 70 years with moderate or severe comorbidity, or aged younger than 70 years with severe comorbidity). Patients were randomly assigned (2:1) by permuted block randomisation (multiples of 6) to intravenous durvalumab 1500 mg starting 2 weeks before radiotherapy then every 4 weeks starting week 2 of radiotherapy (seven cycles) or intravenous cetuximab 400 mg/m<sup>2</sup> 1 week before radiotherapy then 250 mg/m<sup>2</sup> weekly beginning week 1 of radiotherapy (eight cycles), with intensity-modulated radiotherapy (70 Gy in 35 fractions over 7 weeks). Stratification factors were tumour and nodal stage, ECOG performance status and comorbidity, and primary site and p16 status. The phase 2 primary endpoint was progression-free survival in the intention-to-treat population. There was one prespecified interim futility analysis at 50% of progression-free survival information. If the observed hazard ratio was 1·0 or more, favouring cetuximab, early stopping would be considered. Extended follow-up analysis was post hoc. This trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT03258554</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, and is closed to enrolment.<h3>Findings</h3>Following a ten-patient safety lead-in, the phase 2 trial enrolled 190 patients from March 12, 2019, to July 30, 2021, 186 of whom were randomly assigned (123 to durvalumab and 63 to cetuximab). Median age was 72 years (IQR 64–77), 30 (16%) patients were women and 156 (84%) were men. Phase 2 accrual was suspended in July 30, 2021, following an interim futility analysis, and permanently closed in Sept 1, 2022. The phase 3 part of the trial was not conducted. At a median follow-up of 2·3 years (IQR 1·9–3·1)","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637047","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}
Pub Date : 2024-11-14DOI: 10.1016/s1470-2045(24)00592-8
Taymaa May
No Abstract
无摘要
{"title":"Secondary cytoreductive surgery with HIPEC: a promising therapeutic option for recurrent ovarian cancer","authors":"Taymaa May","doi":"10.1016/s1470-2045(24)00592-8","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00592-8","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609765","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":"Investing in cancer care in the UK: why aren't we acting on the evidence?","authors":"Zachary J Ward, Rifat Atun, Ajay Aggarwal, Mark Lawler, Hedvig Hricak","doi":"10.1016/s1470-2045(24)00634-x","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00634-x","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597134","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}
Pub Date : 2024-11-11DOI: 10.1016/s1470-2045(24)00511-4
Luca Mastrantoni, Marta Chiaravalli, Alexia Spring, Viria Beccia, Armando Di Bello, Cinzia Bagalà, Maria Bensi, Diletta Barone, Giovanni Trovato, Giulia Caira, Giulia Giordano, Emilio Bria, Giampaolo Tortora, Lisa Salvatore
<h3>Background</h3>In advanced pancreatic ductal adenocarcinoma (PDAC), first-line chemotherapy is the standard of care. Due to the absence of head-to-head comparisons in clinical trials, we performed this systematic review and network meta-analysis to compare treatment options for PDAC in terms of their efficacy and toxicity.<h3>Methods</h3>PubMed, the Cochrane Central Register of Controlled Trials, Embase, and oncological meetings websites were searched until Nov 15, 2023. We included phase 2–3 randomised controlled trials published after Jan 1, 2000, evaluating first-line treatments in patients with previously untreated, unresectable, locally advanced or metastatic PDAC. Primary endpoints assessed were progression-free survival and overall survival. Summary data were extracted from published reports. The deviance information criterion was used to choose between a random-effects or fixed-effects model. Hazard ratios (HRs) with 95% credible intervals were estimated using a Bayesian approach. The risk of bias was evaluated using the Cochrane Risk of Bias 2 (RoB 2) tool and studies were graded as low, some concerns, or high risk of bias. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. This systematic review and network meta-analysis is registered with PROSPERO, CRD42023450330.<h3>Findings</h3>6050 records were screened and 79 randomised controlled trials (22 168 patients) were included in the analysis. Gemcitabine was the most frequent comparator (in 50 [63%] of 79 trials) and was considered as the reference treatment. A fixed-effect model was used to analyse the primary outcomes. Regarding progression-free survival (71 trials, 19 479 patients), the most effective treatments were gemcitabine plus nab-paclitaxel alternating folinic acid, fluorouracil, and oxaliplatin ([FOLFOX] HR 0·32, 95% credible interval 0·22–0·47), cisplatin, nab-paclitaxel, capecitabine, and gemcitabine ([PAXG] 0·35, 0·22–0·55), and liposomal irinotecan in combination with fluorouracil, leucovorin, and oxaliplatin ([NALIRIFOX] 0·43, 0·34–0·54), followed by fluorouracil, leucovorin, irinotecan, and oxaliplatin ([FOLFIRINOX] 0·55, 0·47–0·65) and gemcitabine plus nab-paclitaxel (0·62, 0·54–0·72). Similar results were observed for overall survival (79 trials, 22 104 patients): PAXG (HR 0·40, 95% credible interval 0·25–0·65), gemcitabine plus nab-paclitaxel alternating FOLFOX (0·46, 0·32–0·66), and NALIRIFOX (0·56, 0·45–0·70) had the highest benefit, followed by FOLFIRINOX (0·66, 0·56–0·78) and gemcitabine plus nab-paclitaxel (0·67, 0·59–0·77). The overall risk of bias was low to some concerns. Certainty of evidence was low.<h3>Interpretation</h3>Our findings suggest that NALIRIFOX and FOLFIRINOX should be the preferred options for patients who can tolerate these regimens, with gemcitabine plus nab-paclitaxel remaining a viable alternative, particularly in patients unfit for triplet therapy. Phase 3 random
{"title":"Comparison of first-line chemotherapy regimens in unresectable locally advanced or metastatic pancreatic cancer: a systematic review and Bayesian network meta-analysis","authors":"Luca Mastrantoni, Marta Chiaravalli, Alexia Spring, Viria Beccia, Armando Di Bello, Cinzia Bagalà, Maria Bensi, Diletta Barone, Giovanni Trovato, Giulia Caira, Giulia Giordano, Emilio Bria, Giampaolo Tortora, Lisa Salvatore","doi":"10.1016/s1470-2045(24)00511-4","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00511-4","url":null,"abstract":"<h3>Background</h3>In advanced pancreatic ductal adenocarcinoma (PDAC), first-line chemotherapy is the standard of care. Due to the absence of head-to-head comparisons in clinical trials, we performed this systematic review and network meta-analysis to compare treatment options for PDAC in terms of their efficacy and toxicity.<h3>Methods</h3>PubMed, the Cochrane Central Register of Controlled Trials, Embase, and oncological meetings websites were searched until Nov 15, 2023. We included phase 2–3 randomised controlled trials published after Jan 1, 2000, evaluating first-line treatments in patients with previously untreated, unresectable, locally advanced or metastatic PDAC. Primary endpoints assessed were progression-free survival and overall survival. Summary data were extracted from published reports. The deviance information criterion was used to choose between a random-effects or fixed-effects model. Hazard ratios (HRs) with 95% credible intervals were estimated using a Bayesian approach. The risk of bias was evaluated using the Cochrane Risk of Bias 2 (RoB 2) tool and studies were graded as low, some concerns, or high risk of bias. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. This systematic review and network meta-analysis is registered with PROSPERO, CRD42023450330.<h3>Findings</h3>6050 records were screened and 79 randomised controlled trials (22 168 patients) were included in the analysis. Gemcitabine was the most frequent comparator (in 50 [63%] of 79 trials) and was considered as the reference treatment. A fixed-effect model was used to analyse the primary outcomes. Regarding progression-free survival (71 trials, 19 479 patients), the most effective treatments were gemcitabine plus nab-paclitaxel alternating folinic acid, fluorouracil, and oxaliplatin ([FOLFOX] HR 0·32, 95% credible interval 0·22–0·47), cisplatin, nab-paclitaxel, capecitabine, and gemcitabine ([PAXG] 0·35, 0·22–0·55), and liposomal irinotecan in combination with fluorouracil, leucovorin, and oxaliplatin ([NALIRIFOX] 0·43, 0·34–0·54), followed by fluorouracil, leucovorin, irinotecan, and oxaliplatin ([FOLFIRINOX] 0·55, 0·47–0·65) and gemcitabine plus nab-paclitaxel (0·62, 0·54–0·72). Similar results were observed for overall survival (79 trials, 22 104 patients): PAXG (HR 0·40, 95% credible interval 0·25–0·65), gemcitabine plus nab-paclitaxel alternating FOLFOX (0·46, 0·32–0·66), and NALIRIFOX (0·56, 0·45–0·70) had the highest benefit, followed by FOLFIRINOX (0·66, 0·56–0·78) and gemcitabine plus nab-paclitaxel (0·67, 0·59–0·77). The overall risk of bias was low to some concerns. Certainty of evidence was low.<h3>Interpretation</h3>Our findings suggest that NALIRIFOX and FOLFIRINOX should be the preferred options for patients who can tolerate these regimens, with gemcitabine plus nab-paclitaxel remaining a viable alternative, particularly in patients unfit for triplet therapy. Phase 3 random","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598517","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}
Pub Date : 2024-11-07DOI: 10.1016/s1470-2045(24)00652-1
Sharmila Devi
No Abstract
无摘要
{"title":"Group of UK MPs urge colleagues to support assisted dying bill","authors":"Sharmila Devi","doi":"10.1016/s1470-2045(24)00652-1","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00652-1","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597136","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}
<h3>Background</h3>Patients with locoregionally advanced nasopharyngeal carcinoma with a high pretreatment plasma concentration of Epstein–Barr virus (EBV) DNA remain at high risk for recurrence after concurrent chemoradiotherapy. This study aimed to compare the efficacy and safety of neoadjuvant–adjuvant treatment with the PD-1 inhibitor toripalimab and concurrent chemoradiotherapy versus placebo and concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma.<h3>Methods</h3>This randomised, single-centre, double-blind, placebo-controlled, phase 2 trial was conducted at Sun Yat-sen University Cancer Centre in Guangzhou, China. Adult patients (aged 18–65 years) with newly diagnosed high-risk stage III–IVa locoregionally advanced nasopharyngeal carcinoma, with a pretreatment plasma EBV DNA concentration of at least 1500 copies per mL and an Eastern Cooperative Oncology Group performance score of 0–1, were eligible. Patients were randomly assigned (2:1) using an interactive web response system (block size of six), stratified by TNM stage (III <em>vs</em> IVa), to neoadjuvant toripalimab (240 mg intravenously) or placebo once every 2 weeks for two cycles, followed by concurrent cisplatin (100 mg/m<sup>2</sup> intravenously) on days 1, 22, and 43 during intensity-modulated radiotherapy and adjuvant toripalimab (240 mg intravenously) or placebo once every 3 weeks for up to eight cycles. The primary endpoint was 2-year progression-free survival in the intention-to-treat population. This study was registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, <span><span>NCT03925090</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, and is closed to enrolment; follow-up is ongoing.<h3>Findings</h3>Between Dec 6, 2019, and Dec 9, 2021, 150 patients were enrolled and randomly assigned to the toripalimab group (n=100) or placebo group (n=50). 115 (77%) patients were male and 35 (23%) were female. As of data cutoff (May 31, 2024), median follow-up for progression-free survival was 37·8 months (IQR 34·2–46·5) for the intention-to-treat population analyses. 2-year progression-free survival was higher in the toripalimab group (92·0% [95% CI 86·7–97·3]) than in the placebo group (74·0% [61·8–86·2]; stratified hazard ratio 0·40 [95% CI 0·18–0·89]; log-rank p=0·019). The most common grade 3 or worse acute adverse events (occurring within 1 year of randomisation) were leukopenia (40 [40%] of 99 patients in the toripalimab group <em>vs</em> 22 [44%] of 50 patients in the placebo group), mucositis (28 [28%] <em>vs</em> ten [20%]), neutropenia (17 [17%] <em>vs</em> nine [18%]), an
背景局部晚期鼻咽癌患者治疗前血浆中爱泼斯坦-巴氏病毒（EBV）DNA浓度较高，同时接受化放疗后复发风险仍然很高。本研究旨在比较PD-1抑制剂托瑞帕利单抗和同期化放疗与安慰剂和同期化放疗对局部晚期鼻咽癌患者进行新辅助治疗的疗效和安全性。方法这项随机、单中心、双盲、安慰剂对照的2期试验在中国广州中山大学肿瘤防治中心进行。新确诊的高危 III-IVa 期局部晚期鼻咽癌成人患者（18-65 岁），治疗前血浆 EBV DNA 浓度至少为 1500 拷贝/毫升，且东部合作肿瘤学组表现评分为 0-1。患者通过交互式网络应答系统（每组6人）进行随机分配（2:1），按TNM分期（III vs IVa）分层，先接受新辅助托瑞帕利单抗（240毫克，静脉注射）或安慰剂治疗，每2周1次，共2个周期，然后在强度调节放疗期间的第1、22和43天同时接受顺铂（100毫克/平方米，静脉注射）治疗，再接受辅助托瑞帕利单抗（240毫克，静脉注射）或安慰剂治疗，每3周1次，最多8个周期。主要终点是意向治疗人群的2年无进展生存期。该研究已在ClinicalTrials.gov注册，编号为NCT03925090，目前已结束注册；随访仍在进行中。研究结果在2019年12月6日至2021年12月9日期间，150名患者注册并随机分配到托利帕单抗组（n=100）或安慰剂组（n=50）。115名（77%）患者为男性，35名（23%）患者为女性。截至数据截止日（2024年5月31日），意向治疗人群分析的无进展生存期中位随访时间为37-8个月（IQR为34-2-46-5）。托瑞帕单抗组的2年无进展生存期（92-0% [95% CI 86-7-97-3]）高于安慰剂组（74-0% [61-8-86-2]；分层危险比0-40 [95% CI 0-18-0-89]；log-rank p=0-019）。最常见的3级或更严重急性不良事件（随机分组后1年内发生）是白细胞减少症（托利帕单抗组99名患者中40[40%]对安慰剂组50名患者中22[44%]）、粘膜炎（28[28%]对10[20%]）、中性粒细胞减少症（17[17%]对9[18%]）、贫血（16[16%]对5[10%]）和体重下降（12[12%]对6[12%]）。最常见的3级或更严重的后期不良事件（随机化后1年）是听觉或听力损失（8[8%] vs 4[8%]）。只有托利帕利单抗组的 10 名患者（10%）发生了 3 级或更严重的免疫介导不良事件。安慰剂组的 50 名患者中有一人（2%）死于与治疗无关的菌血症引起的脓毒性休克。我们的研究结果表明，在治疗局部晚期鼻咽癌时，采用托利帕利单抗（在新辅助治疗和辅助治疗阶段）与同期化放疗相结合的所谓 "三明治 "疗法是一种非常有前景的治疗方法。新辅助和辅助托利帕利单抗与顺铂加吉西他滨新辅助化疗联合同期化放疗的3期非劣效试验值得进行比较。基金项目国家重点研发计划、国家自然科学基金、广东省基础与应用基础研究基金、广州市科技计划、中山大学临床研究5010计划、上海市地方高校高水平创新研究团队、博士后创新人才支持计划、广东省科技计划项目、中山大学青年骨干教师培养计划、中央高校基本科研业务费。
{"title":"Neoadjuvant and adjuvant toripalimab for locoregionally advanced nasopharyngeal carcinoma: a randomised, single-centre, double-blind, placebo-controlled, phase 2 trial","authors":"Sai-Lan Liu, Xiao-Yun Li, Jin-Hao Yang, Dong-Xiang Wen, Shan-Shan Guo, Li-Ting Liu, Yi-Fu Li, Mei-Juan Luo, Si-Yi Xie, Yu-Jing Liang, Xue-Song Sun, Zhen-Chong Yang, Xiao-Fei Lv, Dong-Hua Luo, Ji-Bin Li, Qing Liu, Pan Wang, Ling Guo, Hao-Yuan Mo, Rui Sun, Hai-Qiang Mai","doi":"10.1016/s1470-2045(24)00504-7","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00504-7","url":null,"abstract":"<h3>Background</h3>Patients with locoregionally advanced nasopharyngeal carcinoma with a high pretreatment plasma concentration of Epstein–Barr virus (EBV) DNA remain at high risk for recurrence after concurrent chemoradiotherapy. This study aimed to compare the efficacy and safety of neoadjuvant–adjuvant treatment with the PD-1 inhibitor toripalimab and concurrent chemoradiotherapy versus placebo and concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma.<h3>Methods</h3>This randomised, single-centre, double-blind, placebo-controlled, phase 2 trial was conducted at Sun Yat-sen University Cancer Centre in Guangzhou, China. Adult patients (aged 18–65 years) with newly diagnosed high-risk stage III–IVa locoregionally advanced nasopharyngeal carcinoma, with a pretreatment plasma EBV DNA concentration of at least 1500 copies per mL and an Eastern Cooperative Oncology Group performance score of 0–1, were eligible. Patients were randomly assigned (2:1) using an interactive web response system (block size of six), stratified by TNM stage (III <em>vs</em> IVa), to neoadjuvant toripalimab (240 mg intravenously) or placebo once every 2 weeks for two cycles, followed by concurrent cisplatin (100 mg/m<sup>2</sup> intravenously) on days 1, 22, and 43 during intensity-modulated radiotherapy and adjuvant toripalimab (240 mg intravenously) or placebo once every 3 weeks for up to eight cycles. The primary endpoint was 2-year progression-free survival in the intention-to-treat population. This study was registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT03925090</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, and is closed to enrolment; follow-up is ongoing.<h3>Findings</h3>Between Dec 6, 2019, and Dec 9, 2021, 150 patients were enrolled and randomly assigned to the toripalimab group (n=100) or placebo group (n=50). 115 (77%) patients were male and 35 (23%) were female. As of data cutoff (May 31, 2024), median follow-up for progression-free survival was 37·8 months (IQR 34·2–46·5) for the intention-to-treat population analyses. 2-year progression-free survival was higher in the toripalimab group (92·0% [95% CI 86·7–97·3]) than in the placebo group (74·0% [61·8–86·2]; stratified hazard ratio 0·40 [95% CI 0·18–0·89]; log-rank p=0·019). The most common grade 3 or worse acute adverse events (occurring within 1 year of randomisation) were leukopenia (40 [40%] of 99 patients in the toripalimab group <em>vs</em> 22 [44%] of 50 patients in the placebo group), mucositis (28 [28%] <em>vs</em> ten [20%]), neutropenia (17 [17%] <em>vs</em> nine [18%]), an","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596902","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}
Pub Date : 2024-11-07DOI: 10.1016/s1470-2045(24)00651-x
Emma Wilkinson
No Abstract
无摘要
{"title":"Impact of radiopharmaceutical shortage prompts questions on UK resilience","authors":"Emma Wilkinson","doi":"10.1016/s1470-2045(24)00651-x","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00651-x","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596904","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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