JTO Clinical and Research Reports最新文献_第3页

Addressing Global Disparities in Lung Cancer Screening: Lessons From Puerto Rico and Beyond 解决肺癌筛查的全球差异：来自波多黎各和其他地区的经验教训

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-15 DOI: 10.1016/j.jtocrr.2025.100919

Patrick Goodley MBBChir , Matthew Evison MD

引用次数: 0

Weight, BSA, Toxicity, and Efficacy of Tyrosine Kinase Inhibitors for ALK-Mutated NSCLC alk突变NSCLC中酪氨酸激酶抑制剂的重量、BSA、毒性和疗效

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-10 DOI: 10.1016/j.jtocrr.2025.100918

Beatriz Jimenez Munarriz MD , Sameena Khan MBChB, PhD , Katrina Hueniken MPH, MSc , Shirley Tam MD , Devalben Patel BSc, MLT , Luna Zhan MPH , Catherine Brown MSc , Lawson Eng MD, SM, FRCPC , Adrian Sacher MMSc, MD , Penelope Bradbury MB, BCh, FRACP, MD , Natasha Leighl MMSc, MD, BSc , Geoffrey Liu MSc, MD , Frances A. Shepherd MD, FRCPC

Introduction

ALK tyrosine kinase inhibitors (ALK TKIs) are started at a standard dose regardless of patients’ weight and body surface area (BSA). In this retrospective analysis, the authors explored whether body size variables were associated with toxicity and efficacy.

Methods

Retrospective data for ALK-positive patients at the Princess Margaret Cancer Centre were extracted from electronic health records. Associations between BSA/weight quartiles and dose reductions (DRs), temporary interruptions (TIs), and permanent discontinuation due to toxicity were evaluated using generalized linear mixed modeling. Survival analysis was conducted using Kaplan-Meier curves and log-rank tests.

Results

Among 142 patients with ALK-positive NSCLC treated between July 2012 and March 2024, the median age was 58 years, 54% were female, 78% never-smokers, 49% were Asian, and 37% were Caucasian. A significantly higher proportion of males were in the highest BSA Q4 (89%, p < 0.001), whereas more females (91%, p < 0.001) and Asians were in the lowest BSA Q1 (80%, p < 0.001).

Higher weight at ALK TKI initiation was associated with an increased likelihood of DR at any time (adjusted odds ratio [aOR] = 1.20 per 10-kg increase, 95% confidence interval: 1.0–1.4, p = 0.04), as was having higher BSA (aOR = 2.00 per 0.5-U increase, 95% confidence interval: 1.0–3.9, p = 0.04). TIs were associated with higher weight (10-kg increase, aOR = 1.28, p = 0.006), BMI (5-U BMI increase, aOR = 1.40, p = 0.02), and BSA (0.5-U increase, aOR = 2.59, p = 0.005). These weight/BSA results were statistically significant in patients during alectinib or lorlatinib treatment. In contrast, permanent discontinuation was associated with higher weight/BSA in brigatinib/ceritinib/crizotinib-treated patients. In multivariable analysis, older age and male sex were independently associated with more DRs and TIs. Weight and BSA quartiles were not associated with progression-free survival (p = 0.4) or overall survival (p = 0.6).

Conclusions

Higher weight and larger BSA at the start of ALK TKI treatment were associated with higher likelihood of toxicity, leading to more DRs and TIs—particularly in males and patients receiving alectinib and lorlatinib. However, weight and BSA were not associated with treatment outcomes.

无论患者的体重和体表面积（BSA）如何，ALK酪氨酸激酶抑制剂（ALK TKIs）都以标准剂量开始。在这项回顾性分析中，作者探讨了体型变量是否与毒性和疗效相关。方法从电子健康记录中提取玛格丽特公主癌症中心alk阳性患者的回顾性数据。使用广义线性混合模型评估了BSA/体重四分位数与剂量减少（DRs）、暂时中断（TIs）和因毒性导致的永久停药之间的关系。生存率分析采用Kaplan-Meier曲线和log-rank检验。结果在2012年7月至2024年3月期间接受治疗的142例alk阳性NSCLC患者中，年龄中位数为58岁，54%为女性，78%为从不吸烟者，49%为亚洲人，37%为高加索人。较高比例的男性处于最高BSA Q4 (89%, p < 0.001)，而更多的女性（91%,p < 0.001）和亚洲人处于最低BSA Q1 （80%, p < 0.001）。ALK TKI起始时体重增加与任何时间DR发生的可能性增加相关（校正优势比[aOR] = 1.20 / 10 kg， 95%可信区间：1.0-1.4,p = 0.04）， BSA升高也与之相关（aOR = 2.00 / 0.5 u， 95%可信区间：1.0-3.9,p = 0.04）。TIs与体重增加（10 kg增加，aOR = 1.28, p = 0.006）、BMI （5-U BMI增加，aOR = 1.40, p = 0.02）和BSA （0.5-U增加，aOR = 2.59, p = 0.005）相关。这些体重/BSA结果在阿勒替尼或氯拉替尼治疗的患者中具有统计学意义。相反，永久停药与布加替尼/塞瑞替尼/克唑替尼治疗的患者体重/BSA升高相关。在多变量分析中，年龄和男性与更多的dr和ti独立相关。体重和BSA四分位数与无进展生存期（p = 0.4）或总生存期（p = 0.6）无关。结论ALK - TKI治疗开始时体重越重，BSA越大，毒性可能性越高，导致dr和tis的发生率越高，尤其是在男性和接受alectinib和lorlatinib治疗的患者中。然而，体重和BSA与治疗结果无关。

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引用次数: 0

Rapid-onset Severe Cytokine Release Syndrome With Marked Interleukin-6 Increase and Acute Liver Injury After the First Tarlatamab Dose in SCLC: Case Report SCLC患者首次服用塔拉他单抗后伴白介素-6显著升高和急性肝损伤的快速发作严重细胞因子释放综合征：病例报告

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-10 DOI: 10.1016/j.jtocrr.2025.100917

Kento Takagi MD , Go Saito MD, PhD , Toshiaki Inazaki MD , Hikaru Shojima MD , Jun Miyakoshi MD , Akira Naito MD, PhD , Shun Sato MD, PhD , Takashi Shimazui MD, PhD , Haruka Anzai MD , Chiaki Imai PhD , Takuji Suzuki MD, PhD

Tarlatamab is a novel bispecific T-cell engager therapy with promising efficacy in patients with previously treated extensive-stage SCLC. Cytokine release syndrome (CRS) is the most common adverse event related to tarlatamab, although severe CRS remains rare, and grade 3 or higher adverse events have been reported to be less common with tarlatamab than with chemotherapy. Available clinical data on severe adverse events associated with tarlatamab remain limited. Herein, we report a case of a 55-year-old woman with extensive-stage-SCLC who was treated with tarlatamab. Severe CRS and liver injury rapidly developed in the patient after the first tarlatamab dose, which led to treatment discontinuation. This report also presents the temporal changes in serum interleukin-6 levels, highlighting its potential utility as a biomarker for the onset and severity of CRS.

Tarlatamab是一种新型的双特异性t细胞参与疗法，对先前治疗过的广泛期SCLC患者有很好的疗效。细胞因子释放综合征（CRS）是与塔拉他单抗相关的最常见的不良事件，尽管严重的CRS仍然很少见，据报道，塔拉他单抗的3级或更高的不良事件比化疗更少。可获得的与塔拉他单抗相关的严重不良事件的临床数据仍然有限。在此，我们报告一例55岁的女性大分期sclc患者接受塔拉他单抗治疗。患者在第一次服用塔拉他单抗后迅速出现严重的CRS和肝损伤，导致停药。本报告还介绍了血清白细胞介素-6水平的时间变化，强调了其作为CRS发病和严重程度的生物标志物的潜在效用。

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引用次数: 0

Central Nervous System Progression in Patients Receiving ALK-Targeted Central Nervous System–Penetrable Tyrosine Kinase Inhibitors: Treatment Patterns and Outcomes 接受alk靶向中枢神经系统可穿透酪氨酸激酶抑制剂的患者中枢神经系统进展：治疗模式和结果

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-03 DOI: 10.1016/j.jtocrr.2025.100914

Surbhi Singhal MD , Caressa Hui MD , Joel W. Neal MD, PhD , Seema Nagpal MD , Mohana Roy MD , Millie Das MD , Kavitha Ramchandran MD , Erqi Pollom MD , Giovanni Selvaggi MD , Heather A. Wakelee MD , Nathaniel J. Myall MD

Introduction

Central nervous system (CNS) metastases are common in ALK-rearranged NSCLC. The optimal treatment strategy for patients who develop CNS progression during treatment with CNS-penetrable ALK tyrosine kinase inhibitors (TKIs) is unknown. Here, we characterized practice patterns and outcomes for patients who developed CNS progression during treatment with CNS-penetrable TKI.

Methods

This retrospective study included patients who developed CNS progression (time 0, [T0]) on alectinib, lorlatinib, brigatinib, or ensartinib. Patients were characterized according to TKI management (i.e., TKI unaltered, TKI-altered [switched TKI or increased TKI dose], TKI discontinued) at T0. Intracranial progression-free survival was evaluated using Kaplan-Meier and compared using the log-rank test.

Results

Among 98 patients treated with a CNS-penetrable TKI, 36 (37%) experienced CNS progression. Overall, 33 (92%) developed parenchymal and seven (19%) developed leptomeningeal progression, respectively. At T0, 16 (44%) had TKI unaltered, 14 (39%) had TKI altered (eight switched TKI, six increased TKI dose), and six (17%) discontinued TKI. Patients with TKI-altered tended to have more frequent leptomeningeal disease or concurrent systemic progression at T0. Intracranial radiation was given at T0 in 14 (88%) of TKI-unaltered and three (21%) of TKI-altered patients. The median intracranial progression-free survival from T0 was not significantly different between the TKI-altered versus unaltered groups (p = 0.21).

Conclusions

For patients with ALK-rearranged NSCLC with leptomeningeal progression or concurrent systemic progression, TKI change or dose increase was a feasible salvage strategy for CNS progression during treatment with CNS-penetrable TKI.

中枢神经系统（CNS）转移在alk重排的非小细胞肺癌中很常见。在使用可穿透中枢神经系统的ALK酪氨酸激酶抑制剂（TKIs）治疗期间出现中枢神经系统进展的患者的最佳治疗策略尚不清楚。在这里，我们描述了在CNS可穿透TKI治疗期间出现CNS进展的患者的实践模式和结果。方法本回顾性研究纳入使用阿勒替尼、洛拉替尼、布加替尼或恩沙替尼后出现中枢神经系统进展（时间0，[T0]）的患者。患者的特征根据TKI管理（即TKI未改变，TKI改变[切换TKI或增加TKI剂量]，TKI停止）在T0。颅内无进展生存期采用Kaplan-Meier评估，log-rank检验比较。结果在98例接受CNS穿透TKI治疗的患者中，36例（37%）出现了CNS进展。总体而言，33例（92%）发展为实质，7例（19%）发展为轻脑膜进展。在T0时，16例（44%）患者TKI未改变，14例（39%）TKI改变（8例切换TKI， 6例增加TKI剂量），6例（17%）停用TKI。tki改变的患者往往在T0时有更频繁的小脑膜疾病或并发全身性进展。tki未改变的14例（88%）和tki改变的3例（21%）患者在T0时给予颅内放疗。tki改变组与未改变组T0后的中位颅内无进展生存期无显著差异（p = 0.21）。结论对于alk重排NSCLC伴轻脑膜进展或同时全身进展的患者，在可穿透CNS的TKI治疗期间，改变TKI或增加TKI剂量是一种可行的挽救CNS进展的策略。

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引用次数: 0

Corrigendum to “Associations of Tissue Tumor Mutational Burden and Mutational Status With Clinical Outcomes With Pembrolizumab Plus Chemotherapy Versus Chemotherapy For Metastatic NSCLC [JTO Clinical and Research Reports Vol. 4 No. 1: 100431] “组织肿瘤突变负担和突变状态与Pembrolizumab联合化疗与化疗治疗转移性NSCLC临床结果的关联”的勘误[JTO临床与研究报告Vol. 4 No. 1: 100431]

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-01 DOI: 10.1016/j.jtocrr.2025.100892

Marina C. Garassino MD , Shirish Gadgeel MD , Silvia Novello MD, PhD , Balazs Halmos MD , Enriqueta Felip MD , Giovanna Speranza MD , Rina Hui PhD , Edward B. Garon MD , Hidehito Horinouchi MD, PhD , Shunichi Sugawara MD, PhD , Delvys Rodriguez-Abreu MD, PhD , Martin Reck MD , Razvan Cristescu PhD , Deepti Aurora-Garg PhD , Andrey Loboda PhD , Jared Lunceford PhD , Julie Kobie PhD , Mark Ayers MS , Bilal Piperdi MD , M. Catherine Pietanza MD , Luis Paz-Ares MD, PhD

引用次数: 0

Durable Response to Lenvatinib in Platinum-Refractory Metastatic High-Grade Thymic Mucoepidermoid Carcinoma: A Case Report Lenvatinib对铂难治性转移性高级别胸腺黏液表皮样癌的持久疗效：1例报告

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-10-01 DOI: 10.1016/j.jtocrr.2025.100894

Noa Amin PhD, MRCP , Thanika Ketpueak DM , Simon Jordan MBBCh, MD , Andrew G. Nicholson DM, FRCPath , Yu Zhi Zhang MBBS, PhD, FRCPath , Sanjay Popat PhD FRCP

Thymic mucoepidermoid carcinoma (MEC) is a rare thymic carcinoma subtype. Current metastatic thymic carcinoma guidelines recommend first-line platinum-based chemotherapy. However, evidence suggests that MECs, including those of the lung and salivary gland, are chemorefractory, highlighting a more nuanced approach to systemic therapy decision-making. Here, we report a case of durable partial response to second-line lenvatinib in a patient with metastatic high-grade thymic MEC, refractory to first-line platinum-based chemotherapy, suggesting a potentially preferred first-line role for lenvatinib for this subtype.

胸腺粘液表皮样癌（MEC）是一种罕见的胸腺癌亚型。目前的转移性胸腺癌指南推荐一线铂基化疗。然而，有证据表明，包括肺和唾液腺在内的mec是化疗难治性的，这突出了更细致入微的系统性治疗决策方法。在这里，我们报告了一例转移性高级别胸腺MEC患者对二线lenvatinib的持久部分反应，对一线铂基化疗难治，提示lenvatinib在一线治疗该亚型的潜在首选作用。

引用次数: 0

DLL3 Immunohistochemical Expression in Neuroendocrine-Transformed EGFR-Mutant Lung Cancer and Two Cases of Tarlatamab Therapy DLL3在神经内分泌转化egfr突变肺癌中的免疫组织化学表达及两例塔拉他单抗治疗

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-09-30 DOI: 10.1016/j.jtocrr.2025.100913

Jacqueline V. Aredo MD, MS , Surbhi Singhal MD , Gerald J. Berry MD , Farshad Moradi MD, PhD , Heather A. Wakelee MD , Nathaniel J. Myall MD , Kavitha J. Ramchandran MD , Millie Das MD , Carlos J. Suarez MD, MS , Joel W. Neal MD, PhD , Jonathan W. Riess MD, MS

Introduction

Histologic transformation to high-grade neuroendocrine carcinoma occurs in resistance to EGFR targeted treatment in approximately 3% to 4% of patients with EGFR-mutant lung cancer and is associated with poor outcomes. The bispecific T-cell engager, tarlatamab, targets DLL3 and CD3 and has exhibited activity in classical SCLC. We evaluated DLL3 expression in patients with neuroendocrine-transformed EGFR-mutant lung cancer and present two cases who received tarlatamab.

Methods

Patients with high-grade neuroendocrine EGFR-mutant lung cancer de novo or after treatment with osimertinib were evaluated at two academic centers. DLL3 expression in neuroendocrine tissue was assessed by immunohistochemistry using the VENTANA SP347 assay (Roche Diagnostics International AG, Rotkreuz, Switzerland).

Results

Twelve patients were identified. Initial histologic diagnoses included adenocarcinoma (n = 10), adenosquamous (n = 1), and combined small cell carcinoma with an adenocarcinoma component (n = 1), with eight having EGFR exon 19 deletions and four with EGFR L858R. TP53 co-mutations and RB1 loss were detected in all patients tested (10 and 7, respectively). The median time from osimertinib initiation to neuroendocrine transformation was 27.8 months (range 3.6–52.9). DLL3 expression was positive in 11 patients with 15 samples (median 80%, range 1–100) and negative in one patient. Two patients with small cell transformation and 100% tumor DLL3 expression underwent treatment with tarlatamab with progression; osimertinib was subsequently added to tarlatamab in one patient with substantial improvement in all lesions.

Conclusions

In this study, neuroendocrine-transformed EGFR-mutant lung cancer exhibited variable DLL3 expression. Tarlatamab appeared effective when added to osimertinib. Further analysis of the combination of bispecific DLL3 T-cell engager and EGFR tyrosine kinase inhibitor is warranted to confirm these findings.

大约3% - 4%的EGFR突变型肺癌患者在对EGFR靶向治疗产生耐药性时发生组织学转化为高级别神经内分泌癌，并与不良预后相关。双特异性t细胞参与剂tarlatamab靶向DLL3和CD3，并在经典SCLC中显示出活性。我们评估了神经内分泌转化egfr突变肺癌患者的DLL3表达，并报告了两例接受塔拉他单抗治疗的患者。方法在两个学术中心对新发或经奥西替尼治疗的高级别神经内分泌egfr突变肺癌患者进行评估。采用VENTANA SP347法（Roche Diagnostics International AG, Rotkreuz, Switzerland），通过免疫组织化学方法评估神经内分泌组织中DLL3的表达。结果共鉴定出12例患者。最初的组织学诊断包括腺癌（n = 10）、腺鳞癌（n = 1）和合并腺癌成分的小细胞癌（n = 1），其中8例有EGFR外显子19缺失，4例有EGFR L858R缺失。在所有被检测的患者中均检测到TP53共突变和RB1缺失（分别为10例和7例）。从开始使用奥希替尼到神经内分泌转化的中位时间为27.8个月（范围3.6-52.9）。15例样本中11例患者DLL3表达阳性（中位数80%，范围1-100），1例患者DLL3表达阴性。2例小细胞转化且肿瘤DLL3表达100%的患者接受塔拉他单抗治疗，并进展；随后，一名患者将奥西替尼加入塔拉他单抗，所有病变均有明显改善。结论在本研究中，神经内分泌转化的egfr突变型肺癌呈现可变的DLL3表达。当加入奥西替尼时，塔拉他抗似乎有效。进一步分析双特异性DLL3 t细胞接合剂和EGFR酪氨酸激酶抑制剂的组合有必要证实这些发现。

{"title":"DLL3 Immunohistochemical Expression in Neuroendocrine-Transformed EGFR-Mutant Lung Cancer and Two Cases of Tarlatamab Therapy","authors":"Jacqueline V. Aredo MD, MS , Surbhi Singhal MD , Gerald J. Berry MD , Farshad Moradi MD, PhD , Heather A. Wakelee MD , Nathaniel J. Myall MD , Kavitha J. Ramchandran MD , Millie Das MD , Carlos J. Suarez MD, MS , Joel W. Neal MD, PhD , Jonathan W. Riess MD, MS","doi":"10.1016/j.jtocrr.2025.100913","DOIUrl":"10.1016/j.jtocrr.2025.100913","url":null,"abstract":"<div><h3>Introduction</h3><div>Histologic transformation to high-grade neuroendocrine carcinoma occurs in resistance to EGFR targeted treatment in approximately 3% to 4% of patients with <em>EGFR</em>-mutant lung cancer and is associated with poor outcomes. The bispecific T-cell engager, tarlatamab, targets DLL3 and CD3 and has exhibited activity in classical SCLC. We evaluated DLL3 expression in patients with neuroendocrine-transformed <em>EGFR</em>-mutant lung cancer and present two cases who received tarlatamab.</div></div><div><h3>Methods</h3><div>Patients with high-grade neuroendocrine <em>EGFR</em>-mutant lung cancer <em>de novo</em> or after treatment with osimertinib were evaluated at two academic centers. DLL3 expression in neuroendocrine tissue was assessed by immunohistochemistry using the VENTANA SP347 assay (Roche Diagnostics International AG, Rotkreuz, Switzerland).</div></div><div><h3>Results</h3><div>Twelve patients were identified. Initial histologic diagnoses included adenocarcinoma (n = 10), adenosquamous (n = 1), and combined small cell carcinoma with an adenocarcinoma component (n = 1), with eight having <em>EGFR</em> exon 19 deletions and four with <em>EGFR</em> L858R. <em>TP53</em> co-mutations and <em>RB1</em> loss were detected in all patients tested (10 and 7, respectively). The median time from osimertinib initiation to neuroendocrine transformation was 27.8 months (range 3.6–52.9). DLL3 expression was positive in 11 patients with 15 samples (median 80%, range 1–100) and negative in one patient. Two patients with small cell transformation and 100% tumor DLL3 expression underwent treatment with tarlatamab with progression; osimertinib was subsequently added to tarlatamab in one patient with substantial improvement in all lesions.</div></div><div><h3>Conclusions</h3><div>In this study, neuroendocrine-transformed <em>EGFR</em>-mutant lung cancer exhibited variable DLL3 expression. Tarlatamab appeared effective when added to osimertinib. Further analysis of the combination of bispecific DLL3 T-cell engager and EGFR tyrosine kinase inhibitor is warranted to confirm these findings.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100913"},"PeriodicalIF":3.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145420518","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}

引用次数: 0

RELAY+: Final Overall Survival With Ramucirumab Plus Gefitinib in Patients With Untreated EGFR-Mutated Metastatic NSCLC RELAY+: Ramucirumab加吉非替尼治疗未经治疗的egfr突变转移性NSCLC患者的最终总生存率

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-09-26 DOI: 10.1016/j.jtocrr.2025.100912

Makoto Nishio MD, PhD , Takashi Seto MD, PhD , Martin Reck PhD , Edward B. Garon MD , Kazuto Nishio MD, PhD , Kazuo Kasahara MD, PhD , Kazumi Nishino MD, PhD , Miyako Satouchi MD, PhD , Kiyotaka Yoh MD , Hidetoshi Hayashi MD, PhD , Kazuko Sakai PhD , Sotaro Enatsu MD, PhD , Tomoko Matsui BSc, RPh , Sunoj Chacko Varughese MSc , Michelle Carlsen MS , Carla Visseren-Grul MD , Kazuhiko Nakagawa MD, PhD

Introduction

Ramucirumab (RAM) plus gefitinib (GEF) exhibited favorable efficacy and safety as first-line treatment in the primary analysis of the RELAY+ study of East Asian patients with metastatic EGFR-mutated NSCLC. We report the final overall survival (OS) and safety.

Methods

This open-label, two-period, single-arm exploratory study included patients with untreated NSCLC having EGFR ex19del or L858R mutations and no central nervous system metastasis or EGFR T790M mutation. Patients received RAM (10 mg/kg every 2 wk) plus GEF (250 mg once daily) until disease progression (period 1); patients with disease progression who acquired a T790M mutation received RAM plus osimertinib (80 mg once daily) (period 2).

Results

At final OS data cutoff (October 20, 2023; median follow-up: 42.5 mo), median (95% confidence interval [CI]) OS was 47.4 (35.9‒57.6) months, and the 3-year OS rate was 61.8%. In the L858R and ex19del subgroups, median OS was 51.9 and 38.4 months, and 3-year OS rates were 70.2% and 52.8%, respectively. Overall, 85.4% of patients received subsequent systemic therapy post study treatment discontinuation. Grade 3 or higher treatment-related adverse events (AEs) were reported by 51 (62.2%) patients. The most common grade 3 or higher treatment-emergent AE of special interest was hypertension (25.6%; grade 3 event only). Treatment-emergent T790M rate post progression was 81.3%.

Conclusions

RELAY+ revealed a favorable benefit-risk profile for RAM plus GEF in East Asian patients with untreated EGFR-mutated metastatic NSCLC, supporting RAM plus GEF as an alternative first-line treatment option, particularly in those with an L858R mutation.

在对东亚转移性egfr突变NSCLC患者的RELAY+研究的初步分析中，ramucirumab （RAM）联合吉非替尼（GEF）作为一线治疗显示出良好的疗效和安全性。我们报告最终的总生存期（OS）和安全性。方法：这项开放标签、两期、单臂探索性研究纳入了未经治疗的EGFR ex19del或L858R突变、无中枢神经系统转移或EGFR T790M突变的NSCLC患者。患者接受RAM（每2周10 mg/kg）加GEF（每天250 mg 1次）直至疾病进展（第1期）；获得T790M突变的疾病进展患者接受RAM加奥西替尼（80mg，每日一次）（第2期）。结果最终OS数据截止日期为2023年10月20日，中位随访时间为42.5个月，中位（95%置信区间[CI]） OS为47.4（35.9-57.6）个月，3年OS率为61.8%。在L858R和ex19del亚组中，中位OS分别为51.9和38.4个月，3年OS率分别为70.2%和52.8%。总体而言，85.4%的患者在研究停止治疗后接受了后续的全身治疗。51例（62.2%）患者报告了3级或以上的治疗相关不良事件（ae）。最常见的3级或更高级别治疗引起的AE是高血压（25.6%，仅3级事件）。治疗后出现T790M的比率为81.3%。结论：relay +显示RAM + GEF在东亚未经治疗的egfr突变转移性NSCLC患者中具有良好的获益-风险特征，支持RAM + GEF作为替代一线治疗选择，特别是在L858R突变患者中。

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引用次数: 0

Evaluating Circulating Tumor DNA Clearance as an Early Intermediate End Point Predicting Clinical Benefit in Metastatic Nonsquamous NSCLC After First-Line Chemoimmunotherapy 评估循环肿瘤DNA清除率作为预测转移性非鳞状NSCLC一线化疗免疫治疗后临床获益的早期中间终点

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-09-19 DOI: 10.1016/j.jtocrr.2025.100907

Min Yuan PhD † , Haolun Ding MS † , Weiwei Zhuang PhD , Yaning Yang PhD , Xu Steven Xu PhD

<div><h3>Introduction</h3><div>In the first-line (1L) NSCLC setting, overall survival (OS) as a trial end point is increasingly challenging due to longer survival and confounding from novel later-line therapies. This study aims to evaluate whether circulating tumor DNA (ctDNA) clearance (alone or with radiographic response) is a reliable early surrogate end point for progression-free survival (PFS) and OS in 1L NSCLC studies.</div></div><div><h3>Methods</h3><div>Data from a phase III trial (IMpower150) of patients with untreated metastatic nonsquamous NSCLC were used. ctDNA clearance, unconfirmed radiographic response, and confirmed radiographic response at approximately 6 months after treatment were evaluated as surrogates for PFS and OS. The meta-analytic approaches were used. The data were randomly split into four cohorts, treating each as an independent “trial” to simulate a multi-trial meta-analysis. This process was repeated 50 times for statistical robustness.</div></div><div><h3>Results</h3><div>ctDNA decline correlated with longer PFS and OS, with greater declines associated with better outcomes. Patients achieving ctDNA clearance (CL) by week 21 had the most significant PFS and OS improvements (<em>p</em> < 0.001). Radiographic response (Resp) within 6 months posttreatment was also associated with improved survival. Combined ctDNA_CL and Resp further enhanced prognostic discrimination. When comparing atezolizumab plus bevacizumab plus carboplatin plus paclitaxel versus bevacizumab plus carboplatin plus paclitaxel (BCP), the individual-level association between 6-month ctDNA CL plus Resp and survival yielded a global odds ratio of 2.06 (95% CI: 2.02–2.11) for PFS and 6.08 (95% CI: 5.92–6.23) for OS. Similar global odds ratios were observed for atezolizumab plus carboplatin plus paclitaxel versus BCP. For the atezolizumab plus bevacizumab plus carboplatin plus paclitaxel versus BCP comparison, cohort-level associations between 6-month ctDNA CL plus Resp and PFS were R<sup>2</sup><sub>WLS</sub> = 0.41 (95% CI: 0.33–0.50) and R<sup>2</sup><sub>copula</sub> = 0.38 (95% CI: 0.30–0.45), whereas associations with OS were R<sup>2</sup><sub>WLS</sub> = 0.48 (95% CI: 0.40–0.56) and R<sup>2</sup><sub>copula</sub> = 0.51 (95% CI: 0.43–0.60) at 6 months. Slightly lower cohort-level associations were observed for atezolizumab plus carboplatin plus paclitaxel versus BCP (R<sup>2</sup> = 0.34–0.41).</div></div><div><h3>Conclusion</h3><div>ctDNA decline is associated with improved survival outcomes in a clear dose–response manner. ctDNA clearance and radiologic response provide complementary prognostic information, and combining these end points (ctDNA_CL + Resp) can further improve prediction of PFS and OS. This combination also enhanced the correlation between treatment effects on the early end points and PFS/OS at the trial level. However, their overall ability to predict treatment effects at the trial level remained modest for both PFS and OS, lik

在一线（1L） NSCLC环境中，由于更长的生存期和来自新型后线治疗的混淆，总生存期（OS）作为试验终点越来越具有挑战性。本研究旨在评估在1L NSCLC研究中，循环肿瘤DNA （ctDNA）清除率（单独或结合放射学反应）是否是无进展生存期（PFS）和OS的可靠早期替代终点。方法：使用来自未经治疗的转移性非鳞状NSCLC患者的III期试验（IMpower150）的数据。ctDNA清除率、未确诊的放射学反应和治疗后约6个月的确诊放射学反应被评估为PFS和OS的替代指标。采用元分析方法。数据被随机分成四组，每组作为一个独立的“试验”来模拟多试验荟萃分析。为了统计稳健性，这个过程重复了50次。结果dna下降与较长的PFS和OS相关，下降越大，预后越好。在第21周达到ctDNA清除（CL）的患者有最显著的PFS和OS改善（p < 0.001）。治疗后6个月内的放射学反应（Resp）也与生存率的提高有关。ctDNA_CL和Resp联合使用进一步增强了预后鉴别。当比较阿特唑单抗+贝伐单抗+卡铂+紫杉醇与贝伐单抗+卡铂+紫杉醇（BCP）时，6个月ctDNA CL + Resp与生存之间的个体水平关联产生了PFS的全球优势比为2.06 (95% CI: 2.02-2.11)， OS的全球优势比为6.08 （95% CI: 5.92-6.23）。阿特唑单抗加卡铂加紫杉醇与BCP的全球比值比相似。对于阿特唑单抗+贝伐单抗+卡铂+紫杉醇与BCP的比较，6个月ctDNA CL + Resp和PFS的队列水平相关性为R2WLS = 0.41 （95% CI: 0.33-0.50）和R2copula = 0.38 (95% CI: 0.30-0.45)，而与OS的相关性为6个月时R2WLS = 0.48 （95% CI: 0.40-0.56）和R2copula = 0.51 （95% CI: 0.43-0.60）。阿特唑单抗加卡铂加紫杉醇组与BCP组的队列水平相关性略低（R2 = 0.34-0.41）。结论dna下降与生存结果的改善有明显的剂量-反应关系。ctDNA清除率和放射学反应提供了互补的预后信息，结合这些终点（ctDNA_CL + Resp）可以进一步改善PFS和OS的预测。这种组合也增强了治疗效果在早期终点和试验水平PFS/OS之间的相关性。然而，他们在试验水平预测PFS和OS治疗效果的总体能力仍然有限，可能是由于单一研究的数据有限。需要在更大的多试验数据集中进一步验证ctDNA清除率作为一线NSCLC可靠的早期替代终点。

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引用次数: 0

Durvalumab in Patients With Treatment-Naive Stage IV NSCLC With an ECOG Performance Status of 2 to 3 and High PD-L1 Tumor Expression (IFCT-1802 SAVIMMUNE): A Multicenter Phase 2 Trial Durvalumab在ECOG表现状态为2 - 3和高PD-L1肿瘤表达（IFCT-1802 SAVIMMUNE）的初治期非小细胞肺癌患者中的应用：一项多中心2期试验

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-09-18 DOI: 10.1016/j.jtocrr.2025.100908

Valérie Gounant MD , Laurent Greillier MD, PhD , Céline Mascaux MD, PhD , François Pinquie MD , Delphine Carmier MD , Lionel Moreau MD , Benoît Roch MD , Didier Debieuvre MD , Xavier Dhalluin MD , Etienne Giroux-Leprieur MD, PhD , Elodie Berton MD , Audrey Rabeau MD , Judith Raimbourg MD , Adrien Dixmier MD , Charles Naltet MD , Antoine Khalil MD, PhD , Lynn Ezzeddine MD , Mostafa El Hajjam MD, PhD , Alexandra Langlais MSc , Franck Morin MSc , Michael Duruisseaux MD, PhD

Introduction

Eastern Cooperative Oncology Group performance status 2 to 3 is associated with poor survival and chemotherapy-related adverse events (AEs). The impact of poor PS on the safety and efficacy of immune checkpoint inhibitors has not been elucidated. This study aimed to assess first-line durvalumab in patients with PS 2 to 3 with advanced NSCLC and high programmed cell death-ligand 1 (PD-L1) expression.

Methods

In this single-arm, prospective, multicenter, phase II trial, patients with PS 2 to 3 aged 18 to 75 years with metastatic NSCLC and PD-L1 tumor proportion score more than or equal to 25% received durvalumab until progression or toxicity. Primary end point was safety, that is incidence of grade more than or equal to 3 TRAEs during the first 8 weeks. Secondary end points included blinded independent central review overall response rate, progression-free survival, duration of response, overall survival (OS), and PS improvement at 8 weeks and health-related quality of life.

Results

A total of 50 patients were enrolled. Median follow-up was 26.2 (19.9–35.2) months. Prevalence of grade more than or equal to 3 TRAEs during the first 8 weeks was 10.0% (five of 50, 95% confidence interval [CI] 1.7–18.3), and no grade 5 occurred. Overall response rate at 8 weeks was 26% (95% CI 13.8–38.2). Median duration of response, progression-free survival, and OS were 11.8 months (95% CI, 7.2-not reached), 2.3 months (95% CI 1.7–5.6), and 7.1 months (95% CI 3.9–14.5), respectively. The 12-month OS rate was 40% (95% CI 26.5–53.1). Median OS in patients with PS 2 and PS 3 was 11.4 (95% CI 4.4–32.8) and 3.0 (95% CI 0.2–5.6) months, respectively. Of 27 patients, 12 (44.4%) still receiving durvalumab at 8 weeks had improved PS (p = 0.0096). Mean global QLQ-C30 score significantly increased at 8 weeks.

Conclusions

In patients with a PS of 2 to 3 with advanced NSCLC and high PD-L1 expression, first-line durvalumab was safe with 40% 1-year OS.

东部肿瘤合作组表现状态2 - 3与生存差和化疗相关不良事件（ae）相关。不良PS对免疫检查点抑制剂的安全性和有效性的影响尚未阐明。该研究旨在评估durvalumab在ps2 - 3伴晚期NSCLC和程序性细胞死亡配体1 （PD-L1）高表达患者中的一线治疗效果。在这项单组、前瞻性、多中心、II期试验中，年龄在18至75岁、转移性NSCLC和PD-L1肿瘤比例评分大于或等于25%的PS 2至3患者接受durvalumab治疗，直至进展或出现毒性。主要终点是安全性，即在前8周内超过或等于3个trae级别的发生率。次要终点包括盲法独立中心评价：总缓解率、无进展生存期、缓解持续时间、总生存期（OS）、8周时PS改善和健康相关生活质量。结果共纳入50例患者。中位随访时间为26.2（19.9-35.2）个月。前8周发生≥3级trae的发生率为10.0%(50例中的5例，95%可信区间[CI] 1.7-18.3)，未发生5级trae。8周总缓解率为26% （95% CI 13.8-38.2）。中位缓解持续时间、无进展生存期和OS分别为11.8个月（95% CI， 7.2-未达到）、2.3个月（95% CI 1.7-5.6）和7.1个月（95% CI 3.9-14.5）。12个月OS率为40% （95% CI 26.5-53.1）。ps2和ps3患者的中位生存期分别为11.4个月（95% CI 4.4-32.8）和3.0个月（95% CI 0.2-5.6）。在27例患者中，12例（44.4%）患者在8周时仍接受杜伐单抗治疗，PS得到改善（p = 0.0096）。总体QLQ-C30平均评分在8周时显著升高。结论在PS为2 ~ 3的晚期NSCLC和PD-L1高表达患者中，一线durvalumab是安全的，1年OS为40%。

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