Pub Date : 2024-11-14DOI: 10.1016/s1470-2045(24)00528-x
Sean Miller, Ralph Jiang, Matthew Schipper, Lars G Fritsche, Garth Strohbehn, Beth Wallace, Daria Brinzevich, Virginia Falvello, Benjamin H McMahon, Rafael Zamora-Resendiz, Nithya Ramnath, Xin Dai, Kamya Sankar, Donna M Edwards, Steven G Allen, Shinjae Yoo, Silvia Crivelli, Michael D Green, Alex K Bryant
<h3>Background</h3>Black patients were severely under-represented in the clinical trials that led to the approval of immune checkpoint inhibitors (ICIs) for all cancers. The aim of this study was to characterise the effectiveness and safety of ICIs in Black patients.<h3>Methods</h3>We did a retrospective cohort study of patients in the US Veterans Health Administration (VHA) system's Corporate Data Warehouse containing electronic medical records for all patients who self-identified as non-Hispanic Black or African American (referred to as Black) or non-Hispanic White (referred to as White) and received PD-1, PD-L1, CTLA-4, or LAG-3 inhibitors between Jan 1, 2010, and Dec 31, 2023. Effectiveness outcomes were overall survival, time to treatment discontinuation, and time to next treatment. The safety outcome was the frequency of immune-related adverse events; assessed among a random sample of 1000 Black patients and 1000 White patients, 892 pairs were matched on the basis of baseline characteristics using 1:1 exact matching without replacement. After manual chart review, patients who did not receive ICI therapy or who had inadequate follow-up were excluded. The adjusted effect of race on each effectiveness outcome was assessed in the whole ICI-treated cohort with propensity-weighted Cox regression with robust standard errors. Immune-related adverse events outcomes were analysed in the random matched sample with multivariable Cox regression, adjusting for baseline characteristics.<h3>Findings</h3>We identified 26 398 patients, of whom 4943 (18·7%) patients were Black, 21 455 (81·3%) were White, 895 (3·4%) were female, 25 503 (96·6%) were male, 11 859 (45%) had non-small-cell lung cancer, and 26 045 (98·7%) received PD-1 or PD-L1 inhibitors. As of data cutoff (Aug 28, 2024), median follow-up was 40·3 months (95% CI 38·3–42·3) for Black patients and 43·9 months (43·0–45·1) for White patients. Compared with White patients, Black patients had longer time to treatment discontinuation (2-year unadjusted rates 10·7% [95% CI 9·8–11·7] for Black patients <em>vs</em> 8·6% [8·2–9·0] for White patients; adjusted hazard ratio [HR] 0·91, 95% CI 0·87–0·95, p<0·0001), similar time to next treatment (23·5% [22·3–24·8] for Black patients <em>vs</em> 25·6% [25·0–26·2] for White patients; 1·00, 0·95–1·05, p=0·96), and slightly improved overall survival (36·5% [35·2–38·1] for Black patients <em>vs</em> 36·5% [35·8–37·1]; 0·95, 0·90–0·99, p=0·036). 1710 patients (n=862 Black and n=848 White) were analysed for safety outcomes. Compared with White patients, Black patients had a reduced risk of all-grade immune-related adverse events (unadjusted 2-year rate 33·1% [95% CI 28·9–37·1] <em>vs</em> 44·1% [95% CI 39·1–48·7]; adjusted HR 0·75, 95% CI 0·62–0·90, p=0·0026), immune-related adverse events requiring treatment with systemic steroids (0·61, 0·46–0·81, p=0·00051), and immune-related adverse events resulting in permanent ICI discontinuation (0·58, 0·44–0·78, p=0·00024).
背景黑人患者在导致免疫检查点抑制剂（ICIs）获准用于所有癌症的临床试验中代表性严重不足。我们对美国退伍军人健康管理局（VHA）系统企业数据仓库中的患者进行了一项回顾性队列研究，该数据库包含所有自称为非西班牙裔黑人或非裔美国人（简称黑人）或非西班牙裔白人（简称白人），并在2010年1月1日至2023年12月31日期间接受过PD-1、PD-L1、CTLA-4或LAG-3抑制剂治疗的患者的电子病历。疗效指标为总生存期、终止治疗时间和下次治疗时间。安全性结果是免疫相关不良事件的发生频率；在随机抽取的 1000 名黑人患者和 1000 名白人患者中进行评估，根据基线特征采用 1:1 精确配对法对 892 对患者进行配对，不进行替换。经过人工病历审查，未接受 ICI 治疗或随访不足的患者被排除在外。采用带有稳健标准误差的倾向加权 Cox 回归法评估了整个 ICI 治疗队列中种族对每种疗效结果的调整效应。我们发现了26 398名患者，其中4943人（18-7%）为黑人，21 455人（81-3%）为白人，895人（3-4%）为女性，25 503人（96-6%）为男性，11 859人（45%）患有非小细胞肺癌，26 045人（98-7%）接受了PD-1或PD-L1抑制剂治疗。截至数据截止日（2024年8月28日），黑人患者的中位随访时间为40-3个月（95% CI 38-3-42-3），白人患者的中位随访时间为43-9个月（43-0-45-1）。与白人患者相比，黑人患者中断治疗的时间更长（2 年未调整率黑人患者为 10-7% [95% CI 9-8-11-7] ，白人患者为 8-6% [8-2-9-0]；调整后危险比 [HR] 0-91，95% CI 0-87-0-95，p<；0-0001），下次治疗时间相似（黑人患者为23-5% [22-3-24-8] vs 白人患者为25-6% [25-0-26-2]; 1-00, 0-95-1-05, p=0-96），总生存期略有改善（黑人患者为36-5% [35-2-38-1] vs 36-5% [35-8-37-1]; 0-95, 0-90-0-99, p=0-036）。对1710名患者（黑人患者862人，白人患者848人）进行了安全性结果分析。与白人患者相比，黑人患者发生所有等级免疫相关不良事件的风险较低（未经调整的 2 年不良事件发生率为 33-1% [95% CI 28-9-37-1] vs 44-1% [95% CI 39-1-48-7]；调整后 HR 0-75，95% CI 0-62-0-90，p=0-0026）、需要使用全身类固醇治疗的免疫相关不良事件（0-61，0-46-0-81，p=0-00051）和导致永久停用 ICI 的免疫相关不良事件（0-58，0-44-0-78，p=0-00024）。在对免疫相关不良事件亚型的探索性分析中发现，黑人患者发生结肠炎（0-46，0-27-0-76，p=0-0026）和甲状腺功能亢进或甲状腺功能减退（0-63，0-44-0-90，p=0-011）的风险显著降低，而在分析的其他免疫相关不良事件亚型中未发现显著差异。在使用基于类固醇的免疫相关不良事件定义对整个ICI治疗队列进行分析时，也发现了类似的结果。与白人患者相比，黑人患者的ICI疗效相似，而在全国VHA系统中接受治疗的患者的毒性较低，这可能反映出ICI的治疗比（获益与伤害之比）存在重要差异。我们关于黑人患者毒性降低的研究结果需要进一步调查，以评估其普遍性。
{"title":"Effectiveness and safety of immune checkpoint inhibitors in Black patients versus White patients in a US national health system: a retrospective cohort study","authors":"Sean Miller, Ralph Jiang, Matthew Schipper, Lars G Fritsche, Garth Strohbehn, Beth Wallace, Daria Brinzevich, Virginia Falvello, Benjamin H McMahon, Rafael Zamora-Resendiz, Nithya Ramnath, Xin Dai, Kamya Sankar, Donna M Edwards, Steven G Allen, Shinjae Yoo, Silvia Crivelli, Michael D Green, Alex K Bryant","doi":"10.1016/s1470-2045(24)00528-x","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00528-x","url":null,"abstract":"<h3>Background</h3>Black patients were severely under-represented in the clinical trials that led to the approval of immune checkpoint inhibitors (ICIs) for all cancers. The aim of this study was to characterise the effectiveness and safety of ICIs in Black patients.<h3>Methods</h3>We did a retrospective cohort study of patients in the US Veterans Health Administration (VHA) system's Corporate Data Warehouse containing electronic medical records for all patients who self-identified as non-Hispanic Black or African American (referred to as Black) or non-Hispanic White (referred to as White) and received PD-1, PD-L1, CTLA-4, or LAG-3 inhibitors between Jan 1, 2010, and Dec 31, 2023. Effectiveness outcomes were overall survival, time to treatment discontinuation, and time to next treatment. The safety outcome was the frequency of immune-related adverse events; assessed among a random sample of 1000 Black patients and 1000 White patients, 892 pairs were matched on the basis of baseline characteristics using 1:1 exact matching without replacement. After manual chart review, patients who did not receive ICI therapy or who had inadequate follow-up were excluded. The adjusted effect of race on each effectiveness outcome was assessed in the whole ICI-treated cohort with propensity-weighted Cox regression with robust standard errors. Immune-related adverse events outcomes were analysed in the random matched sample with multivariable Cox regression, adjusting for baseline characteristics.<h3>Findings</h3>We identified 26 398 patients, of whom 4943 (18·7%) patients were Black, 21 455 (81·3%) were White, 895 (3·4%) were female, 25 503 (96·6%) were male, 11 859 (45%) had non-small-cell lung cancer, and 26 045 (98·7%) received PD-1 or PD-L1 inhibitors. As of data cutoff (Aug 28, 2024), median follow-up was 40·3 months (95% CI 38·3–42·3) for Black patients and 43·9 months (43·0–45·1) for White patients. Compared with White patients, Black patients had longer time to treatment discontinuation (2-year unadjusted rates 10·7% [95% CI 9·8–11·7] for Black patients <em>vs</em> 8·6% [8·2–9·0] for White patients; adjusted hazard ratio [HR] 0·91, 95% CI 0·87–0·95, p<0·0001), similar time to next treatment (23·5% [22·3–24·8] for Black patients <em>vs</em> 25·6% [25·0–26·2] for White patients; 1·00, 0·95–1·05, p=0·96), and slightly improved overall survival (36·5% [35·2–38·1] for Black patients <em>vs</em> 36·5% [35·8–37·1]; 0·95, 0·90–0·99, p=0·036). 1710 patients (n=862 Black and n=848 White) were analysed for safety outcomes. Compared with White patients, Black patients had a reduced risk of all-grade immune-related adverse events (unadjusted 2-year rate 33·1% [95% CI 28·9–37·1] <em>vs</em> 44·1% [95% CI 39·1–48·7]; adjusted HR 0·75, 95% CI 0·62–0·90, p=0·0026), immune-related adverse events requiring treatment with systemic steroids (0·61, 0·46–0·81, p=0·00051), and immune-related adverse events resulting in permanent ICI discontinuation (0·58, 0·44–0·78, p=0·00024).","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637046","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)00531-x
Jean-Marc Classe, Pierre Meeus, Delphine Hudry, Romuald Wernert, François Quenet, Frédéric Marchal, Gilles Houvenaeghel, Anne-Sophie Bats, Fabrice Lecuru, Gwenaël Ferron, Cécile Brigand, Dominique Berton, Laurence Gladieff, Florence Joly, Isabelle Ray-Coquard, Sylvaine Durand-Fontanier, Gabriel Liberale, Marc Pocard, Constantin Georgeac, Sébastien Gouy, Olivier Glehen
<h3>Background</h3>Hyperthermic intraperitoneal chemotherapy (HIPEC) at interval cytoreductive surgery for ovarian cancer improves overall survival but its role in recurrent disease is uncertain. We aimed to compare outcomes in patients treated with or without HIPEC during surgery for recurrent ovarian cancer.<h3>Methods</h3>The multicentre, open-label, randomised, phase 3 CHIPOR trial was conducted at 31 sites in France, Belgium, Spain, and Canada, and enrolled patients with first relapse of epithelial ovarian cancer at least 6 months after completing platinum-based chemotherapy. Eligible patients were aged 18 years or older with WHO performance status of less than 2. After six cycles of platinum-based chemotherapy (and optional bevacizumab), patients amenable to complete cytoreductive surgery were randomly assigned centrally in a 1:1 ratio, using a web-based system and a minimisation procedure, during surgery to receive HIPEC (cisplatin 75 mg/m<sup>2</sup> in 2 L/m<sup>2</sup> of serum at 41±1°C for 60 min) or not, stratified by centre, completeness of cytoreduction score, platinum-free interval, and latterly, planned poly(ADP-ribose) polymerase inhibitor use. The primary endpoint was overall survival, analysed on an intention-to-treat basis in all randomly assigned patients. This ongoing 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>NCT01376752</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>.<h3>Findings</h3>Between May 11, 2011, and May 14, 2021, 415 female patients were randomly assigned (207 HIPEC, 208 no HIPEC). At the primary analysis (median follow-up 6·2 years, IQR 4·1–8·1), 268 (65%) patients had died (126 [61%] of 207 in the HIPEC group; 142 [68%] of 208 in the no-HIPEC group). Overall survival was significantly improved with HIPEC (stratified hazard ratio 0·73, 95% CI 0·56–0·96; p=0·024). Median overall survival was 54·3 months (95% CI 41·9–61·7) with HIPEC versus 45·8 months (38·9–54·2) without. Grade 3 or worse adverse events within 60 days after surgery occurred in 102 (49%) of 207 patients receiving HIPEC versus 56 (27%) of 208 receiving no HIPEC, the most common being anaemia (47 [23%] <em>vs</em> 30 [14%]), hepatotoxicity (23 [11%] <em>vs</em> 18 [9%]), electrolyte disturbance (28 [14%] <em>vs</em> two [1%]), and renal failure (20 [10%] <em>vs</em> three [1%]). There were three deaths within 60 days of surgery, all in the no-HIPEC group.<h3>Interpretation</h3>Adding HIPEC to cytoreductive surgery after response to platinum-based chemotherapy at first epithelial ovarian cancer recurrence significantly improved overall survival. When trea
背景卵巢癌细胞减灭术间隔期腹腔内热化疗（HIPEC）可提高总生存率，但其对复发疾病的作用尚不确定。我们的目的是比较复发性卵巢癌手术期间接受或不接受 HIPEC 治疗的患者的疗效。方法 多中心、开放标签、随机、3 期 CHIPOR 试验在法国、比利时、西班牙和加拿大的 31 个地点进行，入选者为完成铂类化疗至少 6 个月后首次复发的上皮性卵巢癌患者。符合条件的患者年龄在 18 岁或以上，WHO 体征表现小于 2 级。在进行了六个周期的铂类化疗（可选择贝伐单抗）后，可进行完全细胞减灭术的患者在手术过程中通过网络系统和最小化程序，按1:1的比例被随机分配接受或不接受HIPEC治疗（顺铂75毫克/平方米，溶于2升/平方米的血清中，温度为41±1°C，时间为60分钟），分层因素包括中心、细胞减灭术评分完成度、无铂间隔时间，以及后来计划使用的多（ADP-核糖）聚合酶抑制剂。主要终点是总生存期，对所有随机分配的患者进行意向治疗分析。2011年5月11日至2021年5月14日期间，415名女性患者被随机分配（207人接受HIPEC治疗，208人未接受HIPEC治疗）。在主要分析中（中位数随访 6-2 年，IQR 4-1-8-1），有 268 名（65%）患者死亡（HIPEC 组 207 人中有 126 人[61%]死亡；无 HIPEC 组 208 人中有 142 人[68%]死亡）。HIPEC可明显提高总生存率（分层危险比为0-73，95% CI为0-56-0-96；P=0-024）。采用HIPEC治疗的中位总生存期为54-3个月（95% CI 41-9-61-7），而不采用HIPEC治疗的中位总生存期为45-8个月（38-9-54-2）。术后60天内，接受HIPEC治疗的207例患者中有102例（49%）发生了3级或更严重的不良事件，而未接受HIPEC治疗的208例患者中有56例（27%）发生了3级或更严重的不良事件，最常见的不良事件是贫血（47例[23%] vs 30例[14%]）、肝毒性（23例[11%] vs 18例[9%]）、电解质紊乱（28例[14%] vs 2例[1%]）和肾功能衰竭（20例[10%] vs 3例[1%]）。首次上皮性卵巢癌复发时，对铂类化疗有反应后，在细胞剥脱手术中加入 HIPEC 可显著提高总生存率。在治疗晚期首次复发的高分化浆液性或高分化子宫内膜样卵巢癌患者时，如果患者可以在专科中心接受完全的细胞减灭术，则应考虑使用铂类HIPEC来延长患者的总生存期。
{"title":"Hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer (CHIPOR): a randomised, open-label, phase 3 trial","authors":"Jean-Marc Classe, Pierre Meeus, Delphine Hudry, Romuald Wernert, François Quenet, Frédéric Marchal, Gilles Houvenaeghel, Anne-Sophie Bats, Fabrice Lecuru, Gwenaël Ferron, Cécile Brigand, Dominique Berton, Laurence Gladieff, Florence Joly, Isabelle Ray-Coquard, Sylvaine Durand-Fontanier, Gabriel Liberale, Marc Pocard, Constantin Georgeac, Sébastien Gouy, Olivier Glehen","doi":"10.1016/s1470-2045(24)00531-x","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00531-x","url":null,"abstract":"<h3>Background</h3>Hyperthermic intraperitoneal chemotherapy (HIPEC) at interval cytoreductive surgery for ovarian cancer improves overall survival but its role in recurrent disease is uncertain. We aimed to compare outcomes in patients treated with or without HIPEC during surgery for recurrent ovarian cancer.<h3>Methods</h3>The multicentre, open-label, randomised, phase 3 CHIPOR trial was conducted at 31 sites in France, Belgium, Spain, and Canada, and enrolled patients with first relapse of epithelial ovarian cancer at least 6 months after completing platinum-based chemotherapy. Eligible patients were aged 18 years or older with WHO performance status of less than 2. After six cycles of platinum-based chemotherapy (and optional bevacizumab), patients amenable to complete cytoreductive surgery were randomly assigned centrally in a 1:1 ratio, using a web-based system and a minimisation procedure, during surgery to receive HIPEC (cisplatin 75 mg/m<sup>2</sup> in 2 L/m<sup>2</sup> of serum at 41±1°C for 60 min) or not, stratified by centre, completeness of cytoreduction score, platinum-free interval, and latterly, planned poly(ADP-ribose) polymerase inhibitor use. The primary endpoint was overall survival, analysed on an intention-to-treat basis in all randomly assigned patients. This ongoing 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>NCT01376752</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>.<h3>Findings</h3>Between May 11, 2011, and May 14, 2021, 415 female patients were randomly assigned (207 HIPEC, 208 no HIPEC). At the primary analysis (median follow-up 6·2 years, IQR 4·1–8·1), 268 (65%) patients had died (126 [61%] of 207 in the HIPEC group; 142 [68%] of 208 in the no-HIPEC group). Overall survival was significantly improved with HIPEC (stratified hazard ratio 0·73, 95% CI 0·56–0·96; p=0·024). Median overall survival was 54·3 months (95% CI 41·9–61·7) with HIPEC versus 45·8 months (38·9–54·2) without. Grade 3 or worse adverse events within 60 days after surgery occurred in 102 (49%) of 207 patients receiving HIPEC versus 56 (27%) of 208 receiving no HIPEC, the most common being anaemia (47 [23%] <em>vs</em> 30 [14%]), hepatotoxicity (23 [11%] <em>vs</em> 18 [9%]), electrolyte disturbance (28 [14%] <em>vs</em> two [1%]), and renal failure (20 [10%] <em>vs</em> three [1%]). There were three deaths within 60 days of surgery, all in the no-HIPEC group.<h3>Interpretation</h3>Adding HIPEC to cytoreductive surgery after response to platinum-based chemotherapy at first epithelial ovarian cancer recurrence significantly improved overall survival. When trea","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"158 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609764","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)00597-7
Naomi Kiyota
No Abstract
无摘要
{"title":"Patients with head and neck cancer unfit for cisplatin—what next?","authors":"Naomi Kiyota","doi":"10.1016/s1470-2045(24)00597-7","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00597-7","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637036","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)00586-2
Kerry L Reynolds, Pauline Funchain
No Abstract
无摘要
{"title":"Retrospective analysis of immunotherapy outcomes in Black patients","authors":"Kerry L Reynolds, Pauline Funchain","doi":"10.1016/s1470-2045(24)00586-2","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00586-2","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637037","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)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}
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