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Real-World Neoadjuvant Treatment Patterns and Outcomes in Resected Non–Small-Cell Lung Cancer 已切除非小细胞肺癌的实际新辅助治疗模式和疗效
IF 3.3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.cllc.2024.03.006
Jessica Donington , Xiaohan Hu , Su Zhang , Yan Song , Ashwini Arunachalam , Diana Chirovsky , Chi Gao , Ari Lerner , Anya Jiang , James Signorovitch , Ayman Samkari

Background

Novel neoadjuvant chemoimmunotherapy treatments are being investigated for locally advanced non–small-cell lung cancer (NSCLC), but real-world outcomes for neoadjuvant treatments are poorly understood. This study examined neoadjuvant treatment patterns, real-world event-free survival (rwEFS) and overall survival (OS) in patients with resected, stage II-III NSCLC in the United States (US).

Methods

This retrospective study identified patients in the SEER–Medicare database (2007-2019) with newly diagnosed stage II, IIIA, and IIIB (N2) NSCLC (AJCC 8th edition) treated with neoadjuvant chemo/chemoradiotherapy and resection (index date: neoadjuvant therapy initiation). Neoadjuvant treatment regimens were described. rwEFS (time from index to first recurrence or death, whichever occurred first) and OS (time from index to death) were summarized by Kaplan–Meier analysis for overall population, by disease stage at diagnosis, and by neoadjuvant treatment modality.

Results

221 patients (stage II, N=70; stage III, N=151) met eligibility criteria. The median follow-up from index was 32.7 months. All patients received neoadjuvant chemotherapy (51%) or chemoradiotherapy (49%) prior to surgery; 97% of patients received platinum-based regimens, among which carboplatin+paclitaxel was the most frequent (45%). In all patients, median rwEFS was 17.6 months and 5-year rwEFS was 20.9%; median OS was 48.5 months and 5-year OS was 44.9%. 71% of patients had disease recurrence during follow-up; among them, 28% developed locoregional recurrence as the first recurrence event.

Conclusions

Patients with resected, stage II-III NSCLC who received neoadjuvant chemo/chemoradiotherapy have high rates of disease recurrence and poor survival outcomes, highlighting need for more effective treatments to improve survival rates.

背景目前正在研究治疗局部晚期非小细胞肺癌(NSCLC)的新型新辅助化疗免疫疗法,但人们对新辅助治疗的实际效果知之甚少。本研究考察了美国 II-III 期 NSCLC 患者的新辅助治疗模式、实际无事件生存期(rwEFS)和总生存期(OS)。方法这项回顾性研究确定了 SEER-Medicare 数据库(2007-2019 年)中新诊断的 II、IIIA 和 IIIB(N2)期 NSCLC(AJCC 第 8 版)患者,这些患者接受了新辅助化疗/放疗和切除术(索引日期:新辅助治疗开始日期)。通过Kaplan-Meier分析总结了总体人群、诊断时的疾病分期以及新辅助治疗方式的rwEFS(从指数到首次复发或死亡的时间,以先发生者为准)和OS(从指数到死亡的时间)。中位随访时间为32.7个月。所有患者在手术前均接受了新辅助化疗(51%)或化放疗(49%);97%的患者接受了以铂类为基础的治疗方案,其中以卡铂+紫杉醇的治疗方案最为常见(45%)。在所有患者中,中位rwEFS为17.6个月,5年rwEFS为20.9%;中位OS为48.5个月,5年OS为44.9%。结论接受新辅助化疗/放疗的II-III期NSCLC切除患者疾病复发率高,生存率低,因此需要更有效的治疗方法来提高生存率。
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引用次数: 0
Utility of 30-Day Mortality Following Systemic Anti-Cancer Treatment as a Quality Indicator in Advanced Lung Cancer 系统抗癌治疗后 30 天死亡率作为晚期肺癌质量指标的效用
IF 3.3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.cllc.2024.04.001
Hayley Nicole Roberts, Benjamin Solomon, Susan Harden, Senthil Lingaratnam, Marliese Alexander

Background

30-day mortality after systemic anti-cancer therapy (SACT) has been suggested as a quality indicator primarily for measuring use of chemotherapy towards the end of life. Utility across different cancer types is unclear, especially when using immunotherapy and targeted therapies.

Methods

This retrospective study included patients with a diagnosis of lung cancer who received palliative-intent SACT at an Australian metropolitan cancer center between 2015 and 2022. Using a prospectively maintained lung cancer database, patient, disease, and treatment characteristics were evaluated against annual 30-day mortality rates following SACT.

Results

1072 patients were identified. Annual 30-day mortality rate after palliative-intent SACT for lung cancer ranged between 9% and 15%, with significant variance between treatment types. Calculated rates of 30-day mortality are higher if longer reporting time periods are used. Patients who died within 30 days of SACT were more likely to have received targeted therapies or immunotherapy as their final line of treatment, have a poorer performance status at diagnosis, and have received multiple lines of treatment.

Conclusions

Our data support differential interpretation of 30-day mortality for quality assurance, especially with regard to lung cancer. Consistency in population and reporting time periods, and accounting for treatment type is crucial if 30-day mortality is to be utilized as cancer care performance quality indicator. Relevance to quality care is questionable in the lung cancer setting.

背景有人建议将全身抗癌疗法(SACT)后30天的死亡率作为一项质量指标,主要用于衡量生命末期化疗的使用情况。这项回顾性研究纳入了2015年至2022年期间在澳大利亚大都会癌症中心接受姑息治疗的肺癌患者。利用前瞻性维护的肺癌数据库,根据SACT后30天的年死亡率评估了患者、疾病和治疗特征。肺癌姑息治疗SACT后的30天年死亡率介于9%和15%之间,不同治疗类型之间存在显著差异。如果使用更长的报告时间段,计算出的 30 天死亡率会更高。在SACT后30天内死亡的患者更有可能接受了靶向治疗或免疫治疗作为最后的治疗方案,诊断时的表现状态较差,并且接受了多种治疗方案。结论我们的数据支持对30天死亡率进行不同的解释,以保证质量,尤其是在肺癌方面。如果要将 30 天死亡率作为癌症治疗绩效质量指标,那么人群和报告时间段的一致性以及对治疗类型的考虑至关重要。在肺癌治疗中,30 天死亡率与医疗质量的相关性值得怀疑。
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引用次数: 0
Current Trial Report: A Multicenter Phase I/Ib study of Capmatinib Plus Trametinib in Patients with Metastatic Non-Small Cell Lung Center Harboring MET exon 14 Skipping Mutations and other MET-Alterations 当前试验报告:卡马替尼加曲美替尼治疗携带 MET 第 14 外显子跳越突变和其他 MET 畸变的转移性非小细胞肺中心患者的多中心 I/Ib 期研究
IF 3.3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.cllc.2024.07.002
Matthew S. Lara, J. Riess, Jonathan W. Goldman, Fei Jiang, T. Bivona, Collin M Blakely
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引用次数: 0
Mutations associated with high-grade irAEs in NSCLC patients receiving immunotherapies 接受免疫疗法的 NSCLC 患者中与高级别 irAEs 相关的基因突变
IF 3.3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.cllc.2024.07.003
Margaret R. Smith, Yuezhu Wang, Caroline B. Dixon, Ralph D'Agostino, Yin Liu, Jimmy Ruiz, George C. Oliver, Lance D Miller, U. Topaloglu, Michael D. Chan, Michael Farris, Jing Su, K. Mileham, Wencheng Li, Jason M. Grayson, T. Lycan, Fei Xing
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引用次数: 0
Video-Assisted Thoracoscopic Surgery Versus Thoracotomy Following Neoadjuvant Immunochemotherapy in Resectable Stage III Non-Small Cell Lung Cancer Among Chinese Populations: A Multi-Center Retrospective Cohort Study 视频辅助胸腔镜手术与新辅助免疫化疗后胸廓切开术治疗中国人群中可切除的 III 期非小细胞肺癌:多中心回顾性队列研究
IF 3.3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.cllc.2024.03.008
Hanbo Pan , Hang Chen , Weicheng Kong , Junwei Ning , Zhen Ge , Yu Tian , Ningyuan Zou , Hongda Zhu , Jiaqi Zhang , Yixing Tao , Zenan Gu , Min Zheng , Guomo Ruan , Long Jiang , Ziming Li , Jia Huang , Chengwei Zhou , Guodong Xu , Qingquan Luo

Background

Immune checkpoint inhibitors have revolutionized non-small cell lung cancer (NSCLC) treatment but may pose greater technical challenges for surgery. This study aims to assess the feasibility and oncological effectiveness of video-assisted thoracoscopic surgery (VATS) for resectable stage III NSCLC after neoadjuvant immunochemotherapy.

Methods

Initial stage IIIA-IIIB NSCLC patients with neoadjuvant immunochemotherapy undergoing either VATS or open lobectomy at 6 medical centers during 2019-2023 were retrospectively identified. Perioperative outcomes and 2-year survival was analyzed. Propensity-score matching (PSM) was employed to balance patient baseline characteristics.

Results

Among the total 143 patients, PSM yielded 62 cases each for VATS and OPEN groups. Induction-related adverse events were comparable between the 2 groups. VATS showed a 14.5% conversion rate. Notably, VATS decreased numeric rating scales for postoperative pain, shortened chest tube duration (5[4-7] vs. 6[5-8] days, P = .021), reduced postoperative comorbidities (21.0% vs. 37.1%, P = .048), and dissected less N1 lymph nodes (5[4-6] vs. 7[5-9], P = .005) compared with thoracotomy. Even when converted, VATS achieves perioperative outcomes equivalent to thoracotomy. Additionally, over a median follow-up of 29.5 months, VATS and thoracotomy demonstrated comparable 2-year recurrence-free survival (77.20% vs. 73.73%, P = .640), overall survival (87.22% vs. 88.00%, P = .738), cumulative incidences of cancer-related death, and recurrence patterns. Subsequent subgroup comparisons and multivariate Cox analysis likewise revealed no statistical difference between VATS and thoracotomy.

Conclusion

VATS is a viable and effective option for resectable stage III NSCLC patients following neoadjuvant immunochemotherapy, leading to decreased surgical-related pain, earlier chest tube removal, reduced postoperative complications, and similar survival outcomes compared to thoracotomy.

免疫检查点抑制剂彻底改变了非小细胞肺癌(NSCLC)的治疗,但可能会给手术带来更大的技术挑战。本研究旨在评估视频辅助胸腔镜手术(VATS)治疗新辅助免疫化疗后可切除的III期NSCLC的可行性和肿瘤学效果。回顾性地确定了2019-2023年间在6个医疗中心接受VATS或开胸肺叶切除术的新辅助免疫化疗的IIIA-IIIB期NSCLC初治患者。分析了围手术期结果和2年生存率。采用倾向分数匹配(PSM)来平衡患者的基线特征。在总共143名患者中,PSM得出VATS组和OPEN组各62例。两组患者的诱导相关不良事件相当。VATS 的转换率为 14.5%。值得注意的是,与开胸手术相比,VATS 减少了术后疼痛的数字评分量表,缩短了胸管持续时间(5[4-7] 6[5-8] 天,= .021),减少了术后并发症(21.0% 37.1%,= .048),切除的 N1 淋巴结较少(5[4-6] 7[5-9], = .005)。即使进行转换,VATS 的围手术期结果也与开胸手术相当。此外,在中位随访 29.5 个月期间,VATS 和开胸手术的 2 年无复发生存率(77.20% 73.73%,= .640)、总生存率(87.22% 88.00%,= .738)、癌症相关死亡累积发生率和复发模式均相当。随后的亚组比较和多变量考克斯分析同样显示,VATS 和开胸手术之间没有统计学差异。对于接受新辅助免疫化疗的可切除 III 期 NSCLC 患者来说,VATS 是一种可行且有效的选择,与开胸手术相比,VATS 可减少手术相关疼痛,提前拔除胸管,减少术后并发症,并获得相似的生存结果。
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引用次数: 0
Clinical Outcomes of Patients with Non-Small Cell Lung Cancer Leptomeningeal Disease Following Receipt of EGFR-Targeted Therapy, Immune-Checkpoint Blockade, Intrathecal Chemotherapy, or Radiation Therapy Alone 非小细胞肺癌胸膜疾病患者接受表皮生长因子受体靶向疗法、免疫检查点阻断疗法、鞘内化疗或单纯放疗后的临床疗效
IF 3.3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.cllc.2024.04.005
Matthew N. Mills , Akihiro Uno , Pinxue Li , Casey Liveringhouse , Youngchul Kim , Daniel E. Oliver , Bradford A. Perez , Benjamin C. Creelan , Michael Yu , Peter A. Forsyth , Yolanda Pina , Kamran A. Ahmed

Background

EGFR-targeted therapy (ETT) and immune-checkpoint blockade (ICB) have shown promising results in treating NSCLC brain metastases (BM). However, little is known of their effect in treating leptomeningeal disease (LMD).

Patients and Methods

This is a retrospective review of 80 patients diagnosed with NSCLC LMD from January 2014 to March 2021. Patients were grouped based on initial LMD treatment: radiotherapy (RT) alone, ETT, ICB, and intrathecal chemotherapy (ITC).

Results

EGFR mutation was present in 22 patients (28%). Twenty patients had positive cytology in cerebrospinal fluid, while 60 patients were diagnosed based on MRI with clinical correlation. The RT alone group consisted primarily of whole brain radiation (n = 20; 77%), stereotactic radiation (n = 3; 12%), and palliative spine radiation (n = 2; 7%). There were no significant differences amongst the treatment groups in age, performance status, or neurologic symptoms. Overall, the 6-month overall survival (OS) and craniospinal progression free survival (CS-PFS) were 35% and 24%, respectively. The 6-month OS for the ETT, ICB, ITC, and RT alone groups was 64%, 33%, 57%, and 29% respectively (log-rank P = .026). The 6-month CS-PFS for the ETT, ICB, ITC, and RT alone groups was 43%, 33%, 29%, and 19% respectively (log-rank P = .049). Upon univariate analysis, receipt of ETT compared to RT alone reached significance for OS (HR 0.35, P = .006) and CS-PFS (HR 0.39, P = .013).

Conclusions

The prognosis for patients with NSCLC LMD remains poor overall. However, the receipt of ETT for patients with EGFR-positive disease was associated with improved outcomes.

背景EGFR靶向疗法(ETT)和免疫检查点阻断疗法(ICB)在治疗NSCLC脑转移瘤(BM)方面取得了可喜的成果。患者和方法这是一项回顾性研究,研究对象是2014年1月至2021年3月期间确诊为NSCLC LMD的80例患者。患者根据最初的LMD治疗分组:单纯放疗(RT)、ETT、ICB和鞘内化疗(ITC)。20例患者脑脊液细胞学检查呈阳性,60例患者根据核磁共振成像和临床相关性确诊。单纯 RT 组主要包括全脑放射(20 人;77%)、立体定向放射(3 人;12%)和脊柱姑息放射(2 人;7%)。各治疗组在年龄、表现状态或神经系统症状方面无明显差异。总体而言,6 个月总生存期(OS)和颅骨无进展生存期(CS-PFS)分别为 35% 和 24%。ETT组、ICB组、ITC组和单纯RT组的6个月OS分别为64%、33%、57%和29%(log-rank P = .026)。ETT组、ICB组、ITC组和单纯RT组的6个月CS-PFS分别为43%、33%、29%和19%(对数秩P = .049)。经单变量分析,与单纯 RT 相比,接受 ETT 对 OS(HR 0.35,P = .006)和 CS-PFS (HR 0.39,P = .013)具有显著性意义。然而,表皮生长因子受体阳性患者接受 ETT 治疗可改善预后。
{"title":"Clinical Outcomes of Patients with Non-Small Cell Lung Cancer Leptomeningeal Disease Following Receipt of EGFR-Targeted Therapy, Immune-Checkpoint Blockade, Intrathecal Chemotherapy, or Radiation Therapy Alone","authors":"Matthew N. Mills ,&nbsp;Akihiro Uno ,&nbsp;Pinxue Li ,&nbsp;Casey Liveringhouse ,&nbsp;Youngchul Kim ,&nbsp;Daniel E. Oliver ,&nbsp;Bradford A. Perez ,&nbsp;Benjamin C. Creelan ,&nbsp;Michael Yu ,&nbsp;Peter A. Forsyth ,&nbsp;Yolanda Pina ,&nbsp;Kamran A. Ahmed","doi":"10.1016/j.cllc.2024.04.005","DOIUrl":"10.1016/j.cllc.2024.04.005","url":null,"abstract":"<div><h3>Background</h3><p>EGFR-targeted therapy (ETT) and immune-checkpoint blockade (ICB) have shown promising results in treating NSCLC brain metastases (BM). However, little is known of their effect in treating leptomeningeal disease (LMD).</p></div><div><h3>Patients and Methods</h3><p>This is a retrospective review of 80 patients diagnosed with NSCLC LMD from January 2014 to March 2021. Patients were grouped based on initial LMD treatment: radiotherapy (RT) alone, ETT, ICB, and intrathecal chemotherapy (ITC).</p></div><div><h3>Results</h3><p>EGFR mutation was present in 22 patients (28%). Twenty patients had positive cytology in cerebrospinal fluid, while 60 patients were diagnosed based on MRI with clinical correlation. The RT alone group consisted primarily of whole brain radiation (<em>n =</em> 20; 77%), stereotactic radiation (<em>n =</em> 3; 12%), and palliative spine radiation (<em>n =</em> 2; 7%). There were no significant differences amongst the treatment groups in age, performance status, or neurologic symptoms. Overall, the 6-month overall survival (OS) and craniospinal progression free survival (CS-PFS) were 35% and 24%, respectively. The 6-month OS for the ETT, ICB, ITC, and RT alone groups was 64%, 33%, 57%, and 29% respectively (log-rank <em>P</em> = .026). The 6-month CS-PFS for the ETT, ICB, ITC, and RT alone groups was 43%, 33%, 29%, and 19% respectively (log-rank <em>P</em> = .049). Upon univariate analysis, receipt of ETT compared to RT alone reached significance for OS (HR 0.35, <em>P</em> = .006) and CS-PFS (HR 0.39, <em>P</em> = .013).</p></div><div><h3>Conclusions</h3><p>The prognosis for patients with NSCLC LMD remains poor overall. However, the receipt of ETT for patients with EGFR-positive disease was associated with improved outcomes.</p></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140774183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Treatment-Switching Adjustment of Overall Survival in CheckMate 227 Part 1 Evaluating First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy for Metastatic Nonsmall Cell Lung Cancer CheckMate 227 第一部分评估转移性非小细胞肺癌一线 Nivolumab 加 Ipilimumab 与化疗的总生存期治疗转换调整试验
IF 3.6 3区 医学 Q2 ONCOLOGY Pub Date : 2024-06-29 DOI: 10.1016/j.cllc.2024.06.005
Martin Reck, Tuli De, Luis Paz-Ares, Mark Edmondson-Jones, Yong Yuan, Georgia Yates, Roberto Zoffoli, Mohammad Ashraf Chaudhary, Adam Lee, Nebibe Varol, John R. Penrod
CheckMate 227 (NCT02477826) evaluated first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic nonsmall cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) expression ≥ 1% or < 1% and no / alterations. However, many patients randomized to chemotherapy received subsequent immunotherapy. Here, overall survival (OS) and relative OS benefit of nivolumab-plus-ipilimumab were adjusted for potential bias introduced by treatment switching. Treatment-switching adjustment analyses were conducted following the NICE Decision Support Unit Technical Support Document 16, for CheckMate 227 Part 1 OS data from treated patients (database lock, July 2, 2019). Inverse probability of censoring weighting (IPCW) was used in the base-case analysis; other methods were explored as sensitivity analyses. Of 1166 randomized patients, 391 (PD-L1 ≥ 1%) and 185 (PD-L1 < 1%) patients received nivolumab-plus-ipilimumab; 387 (PD-L1 ≥ 1%) and 183 (PD-L1 < 1%) patients received chemotherapy, with 29.3-month minimum follow-up. Among chemotherapy-treated patients, 169/387 (43.7%; PD-L1 ≥ 1%) and 66/183 (36.1%; PD-L1 < 1%) switched to immunotherapy poststudy. Among treated patients, median OS was 17.4 months with nivolumab-plus-ipilimumab versus 14.9 months with chemotherapy (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.68-0.95) in the PD-L1 ≥ 1% subgroup and 17.1 versus 12.4 months (HR, 0.62; 95% CI, 0.49-0.80) in the PD-L1 < 1% subgroup. After treatment-switching adjustment using IPCW, the HR (95%CI) for OS for nivolumab-plus-ipilimumab versus chemotherapy was reduced to 0.68 (0.56-0.83; PD-L1 ≥ 1%) and 0.53 (0.40-0.69; PD-L1 < 1%). Sensitivity analyses supported the robustness of the results. Treatment-switching adjustments resulted in a greater estimated relative OS benefit with first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic NSCLC.
CheckMate 227 (NCT02477826)评估了程序性死亡配体1(PD-L1)表达≥1%或<1%且无/改变的转移性非小细胞肺癌(NSCLC)患者的一线nivolumab-plus-ipilimumab与化疗的对比。然而,许多随机接受化疗的患者随后又接受了免疫疗法。在此,对nivolumab-plus-ipilimumab的总生存期(OS)和相对OS获益进行了调整,以消除治疗转换带来的潜在偏差。治疗转换调整分析是根据NICE决策支持部门技术支持文件16,针对CheckMate 227第1部分治疗患者的OS数据(数据库锁定时间为2019年7月2日)进行的。在基础案例分析中使用了逆概率删减加权法(IPCW);在敏感性分析中探讨了其他方法。在1166例随机患者中,391例(PD-L1≥1%)和185例(PD-L1<1%)患者接受了nivolumab-plus-ipilimumab治疗;387例(PD-L1≥1%)和183例(PD-L1<1%)患者接受了化疗,随访时间最短为29.3个月。化疗患者中,169/387(43.7%;PD-L1≥1%)和66/183(36.1%;PD-L1<1%)人在研究后转为免疫疗法。在接受治疗的患者中,PD-L1≥1%亚组中,nivolumab加伊匹单抗的中位OS为17.4个月,化疗为14.9个月(危险比[HR],0.80;95%置信区间[CI],0.68-0.95);PD-L1<1%亚组中,中位OS为17.1个月,化疗为12.4个月(HR,0.62;95% CI,0.49-0.80)。使用IPCW进行治疗转换调整后,nivolumab加伊匹单抗与化疗相比的OS HR(95%CI)分别降至0.68(0.56-0.83;PD-L1≥1%)和0.53(0.40-0.69;PD-L1<1%)。敏感性分析证实了结果的稳健性。在转移性NSCLC患者中,治疗转换调整使一线nivolumab-plus-ipilimumab相对于化疗的估计相对OS获益更大。
{"title":"Treatment-Switching Adjustment of Overall Survival in CheckMate 227 Part 1 Evaluating First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy for Metastatic Nonsmall Cell Lung Cancer","authors":"Martin Reck, Tuli De, Luis Paz-Ares, Mark Edmondson-Jones, Yong Yuan, Georgia Yates, Roberto Zoffoli, Mohammad Ashraf Chaudhary, Adam Lee, Nebibe Varol, John R. Penrod","doi":"10.1016/j.cllc.2024.06.005","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.06.005","url":null,"abstract":"CheckMate 227 (NCT02477826) evaluated first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic nonsmall cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) expression ≥ 1% or < 1% and no / alterations. However, many patients randomized to chemotherapy received subsequent immunotherapy. Here, overall survival (OS) and relative OS benefit of nivolumab-plus-ipilimumab were adjusted for potential bias introduced by treatment switching. Treatment-switching adjustment analyses were conducted following the NICE Decision Support Unit Technical Support Document 16, for CheckMate 227 Part 1 OS data from treated patients (database lock, July 2, 2019). Inverse probability of censoring weighting (IPCW) was used in the base-case analysis; other methods were explored as sensitivity analyses. Of 1166 randomized patients, 391 (PD-L1 ≥ 1%) and 185 (PD-L1 < 1%) patients received nivolumab-plus-ipilimumab; 387 (PD-L1 ≥ 1%) and 183 (PD-L1 < 1%) patients received chemotherapy, with 29.3-month minimum follow-up. Among chemotherapy-treated patients, 169/387 (43.7%; PD-L1 ≥ 1%) and 66/183 (36.1%; PD-L1 < 1%) switched to immunotherapy poststudy. Among treated patients, median OS was 17.4 months with nivolumab-plus-ipilimumab versus 14.9 months with chemotherapy (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.68-0.95) in the PD-L1 ≥ 1% subgroup and 17.1 versus 12.4 months (HR, 0.62; 95% CI, 0.49-0.80) in the PD-L1 < 1% subgroup. After treatment-switching adjustment using IPCW, the HR (95%CI) for OS for nivolumab-plus-ipilimumab versus chemotherapy was reduced to 0.68 (0.56-0.83; PD-L1 ≥ 1%) and 0.53 (0.40-0.69; PD-L1 < 1%). Sensitivity analyses supported the robustness of the results. Treatment-switching adjustments resulted in a greater estimated relative OS benefit with first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic NSCLC.","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141785167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MDT-BRIDGE: Neoadjuvant Durvalumab Plus Chemotherapy Followed by Either Surgery and Adjuvant Durvalumab or Chemoradiotherapy and Consolidation Durvalumab in Resectable or Borderline-resectable Stage IIB–IIIB NSCLC MDT-BRIDGE:可切除或边缘可切除的 IIB-IIIB 期 NSCLC 新辅助杜瓦鲁单抗加化疗,然后进行手术和辅助杜瓦鲁单抗或化疗和巩固杜瓦鲁单抗治疗
IF 3.3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-06-21 DOI: 10.1016/j.cllc.2024.06.007

Introduction

In the AEGEAN trial, neoadjuvant durvalumab plus platinum-based chemotherapy (D+CT) followed by adjuvant durvalumab, versus neoadjuvant chemotherapy alone, significantly improved pathological complete response (pCR) rate and event-free survival (EFS) in patients with resectable NSCLC. In the PACIFIC trial, consolidation durvalumab significantly improved progression-free (PFS) and overall survival (OS) for patients with unresectable stage III NSCLC after chemoradiotherapy. Strong pathological and clinical outcomes with chemoimmunotherapy have generated interest in its use to enable patients with borderline-resectable NSCLC to undergo surgery. Additionally, for patients initially deemed resectable but who later become unresectable/inoperable during neoadjuvant treatment, consolidation immunotherapy after chemoradiotherapy should be explored.

Patients and methods

MDT-BRIDGE (NCT05925530) is a multicenter, phase II, non-randomized study in ∼140 patients with EGFR/ALK wild-type, stage IIB–IIIB (N2) NSCLC. Following baseline multidisciplinary team (MDT) assessment to determine resectable/borderline-resectable status, all patients receive 2 cycles of neoadjuvant D+CT every 3 weeks, followed by MDT reassessment of resectability. Patients deemed resectable receive 1-2 additional cycles of D+CT followed by surgery (Cohort 1). Patients deemed unresectable receive standard-of-care chemoradiotherapy (Cohort 2). Cohort 1 patients who become ineligible for surgery can enter Cohort 2. Following surgery or chemoradiotherapy, patients receive adjuvant or consolidation durvalumab for 1 year. The primary endpoint is resection rate in all patients. Additional endpoints include resection rates by baseline resectable/borderline-resectable status, resection outcomes, EFS/PFS, OS, pCR rate, circulating tumor DNA dynamics pre- and post-surgery (including correlation with clinical outcomes), and safety.

Conclusion

Enrollment began in February 2024; primary completion is anticipated in April 2026.

在AEGEAN试验中,新辅助杜伐单抗加铂类化疗(D+CT)后再辅助杜伐单抗与单纯新辅助化疗相比,可显著改善可切除NSCLC患者的病理完全反应率(pCR)和无事件生存期(EFS)。在PACIFIC试验中,对于化疗后无法切除的III期NSCLC患者,durvalumab巩固治疗可明显改善无进展生存期(PFS)和总生存期(OS)。化疗免疫疗法在病理和临床方面的良好疗效引起了人们的兴趣,人们希望通过化疗免疫疗法使边缘可切除的 NSCLC 患者能够接受手术治疗。此外,对于最初被认为可切除但后来在新辅助治疗期间无法切除/无法手术的患者,应探讨在化放疗后进行巩固性免疫治疗。MDT-BRIDGE(NCT05925530)是一项多中心、II期、非随机研究,研究对象为140例/野生型、IIB-IIIB期(N2)NSCLC患者。在多学科小组(MDT)进行基线评估以确定可切除/边缘可切除状态后,所有患者接受2个周期的新辅助D+CT治疗,每3周一次,然后由MDT重新评估可切除性。认为可切除的患者再接受1-2个周期的D+CT治疗,然后进行手术(队列1)。无法切除的患者接受标准化疗放疗(队列 2)。不符合手术条件的队列 1 患者可进入队列 2。手术或化放疗后,患者将接受为期一年的辅助或巩固性杜瓦鲁单抗治疗。主要终点是所有患者的切除率。其他终点包括基线可切除/边缘可切除状态下的切除率、切除结果、EFS/PFS、OS、pCR 率、手术前后循环肿瘤 DNA 动态(包括与临床结果的相关性)以及安全性。该研究于 2024 年 2 月开始入组,预计于 2026 年 4 月完成初选。
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引用次数: 0
Refining Surveillance Guidelines after Stereotactic Body Radiation Therapy for Early-Stage Lung Cancer 完善早期肺癌立体定向体外放射治疗后的监测指南
IF 3.3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-06-21 DOI: 10.1016/j.cllc.2024.06.008

Introduction

Stereotactic body radiation therapy (SBRT) is a treatment for patients with early-stage non-small cell lung cancer (ES-NSCLC). Surveillance guidelines vary after treatment. While patients are more likely to locally recur within 2 years of treatment, there remains a paucity of data on the benefit of frequent and long-term surveillance. We evaluated a cohort of NSCLC patients to evaluate surveillance patterns and outcomes.

Materials and methods

Patients with ES-NSCLC treated with SBRT were retrospectively evaluated. Imaging was reviewed after SBRT for evidence of recurrence or new malignancy. The median scan interval (MSI) was calculated as the median number of months between surveillance scans. The MSI between patients with or without new disease was compared by t-test. New disease development and survival between patients with <T2 or >=T2 disease and with or without prior malignancy was compared using χ², Kaplan-Meier analysis, and Gray's test.

Results

A cohort of 168 patients with median follow up of 23.4 months met criteria for review with 50% developing new disease. MSI did not differ between patients with or without new disease. Patients with >=cT2 tumors had worse overall survival and trended towards higher incidence of new disease. New disease continued to occur, even 5 years after treatment.

Conclusion

Increased scan frequency did not increase detection of new disease. Patients continued to fail 5 years after treatment. Larger tumors trended toward more frequent failures and those patients experienced worse OS. Surveillance guidelines should be optimized to prevent over surveillance after treatment and to continue long-term surveillance.

立体定向体放射治疗(SBRT)是一种针对早期非小细胞肺癌(ES-NSCLC)患者的治疗方法。治疗后的监测指南各不相同。虽然患者更有可能在治疗后两年内局部复发,但关于频繁和长期监测的益处的数据仍然很少。我们对一组 NSCLC 患者进行了评估,以评价监测模式和结果。我们对接受 SBRT 治疗的 ES-NSCLC 患者进行了回顾性评估。在 SBRT 治疗后对影像学进行复查,以寻找复发或新恶性肿瘤的证据。中位扫描间隔(MSI)计算为两次监测扫描之间的中位月数。有无新发疾病患者的中位扫描间隔(MSI)通过 t 检验进行比较。使用χ²、Kaplan-Meier分析和格雷氏检验比较了患有=T2疾病和既往患有或未患有恶性肿瘤的患者的新疾病发生率和存活率。168例患者的中位随访时间为23.4个月,其中50%的患者符合复查标准,并出现了新的疾病。有无新发疾病的患者之间的 MSI 没有差异。肿瘤>=cT2的患者总生存率较低,新发疾病的发生率也呈上升趋势。即使在治疗5年后,新的疾病仍会发生。增加扫描频率并不能提高新疾病的发现率。患者在治疗5年后仍会失败。肿瘤较大的患者治疗失败的频率更高,而这些患者的OS更差。应优化监测指南,防止治疗后过度监测,并继续进行长期监测。
{"title":"Refining Surveillance Guidelines after Stereotactic Body Radiation Therapy for Early-Stage Lung Cancer","authors":"","doi":"10.1016/j.cllc.2024.06.008","DOIUrl":"10.1016/j.cllc.2024.06.008","url":null,"abstract":"<div><h3>Introduction</h3><p>Stereotactic body radiation therapy (SBRT) is a treatment for patients with early-stage non-small cell lung cancer (ES-NSCLC). Surveillance guidelines vary after treatment. While patients are more likely to locally recur within 2 years of treatment, there remains a paucity of data on the benefit of frequent and long-term surveillance. We evaluated a cohort of NSCLC patients to evaluate surveillance patterns and outcomes.</p></div><div><h3>Materials and methods</h3><p><span>Patients with ES-NSCLC treated with SBRT were retrospectively evaluated. Imaging was reviewed after SBRT for evidence of recurrence or new malignancy. The median scan interval (MSI) was calculated as the median number of months between surveillance scans. The MSI between patients with or without new disease was compared by t-test. New </span>disease development and survival between patients with &lt;T2 or &gt;=T2 disease and with or without prior malignancy was compared using χ², Kaplan-Meier analysis, and Gray's test.</p></div><div><h3>Results</h3><p>A cohort of 168 patients with median follow up of 23.4 months met criteria for review with 50% developing new disease. MSI did not differ between patients with or without new disease. Patients with &gt;=cT2 tumors had worse overall survival and trended towards higher incidence of new disease. New disease continued to occur, even 5 years after treatment.</p></div><div><h3>Conclusion</h3><p>Increased scan frequency did not increase detection of new disease. Patients continued to fail 5 years after treatment. Larger tumors trended toward more frequent failures and those patients experienced worse OS. Surveillance guidelines should be optimized to prevent over surveillance after treatment and to continue long-term surveillance.</p></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141566757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular Characteristics and Pretreatment Neutrophil-to-Lymphocyte Ratio as Predictors of Durable Clinical Benefit from Immune Checkpoint Inhibition in Non-Small Cell Lung Cancer 分子特征和治疗前中性粒细胞与淋巴细胞比率是非小细胞肺癌患者从免疫检查点抑制疗法中获得持久临床获益的预测因素
IF 3.3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-06-19 DOI: 10.1016/j.cllc.2024.06.006

Background

Prior research in non-small cell lung cancer (NSCLC) has shown that tumors with specific driver mutations may be less likely to respond to immune checkpoint inhibitors (ICI). In this analysis, we evaluated the characteristics of patients with durable clinical benefit (DCB) to ICI compared to those with no durable clinical benefit (NDB), with emphasis on the role of molecular alterations in EGFR, ALK, and ROS1 and pretreatment neutrophil-to-lymphocyte ratio (NLR).

Methods

We retrospectively collected clinical characteristics and outcomes for patients who initiated ICI monotherapy for advanced NSCLC at Stanford University between April 2015 and May 2018. Patients were classified as having DCB if time on ICI therapy was greater than or equal to 180 days, or NDB if less than 180 days. Outcomes included best radiographic benefit while on ICI and survival from time of ICI initiation.

Results

Of 123 patients treated with ICI for NSCLC, 28 patients had DCB (23%), while 95 had NDB (77%). Median overall survival from initiation of ICI in the 33 patients with molecular alterations in EGFR (n = 31), ALK, or ROS1 and NLR of 5.9 or higher was 2.0 months, compared to 8.1 months in patients with these genomic alterations and NLR less than 5.9. Median overall survival in patients without alterations in EGFR, ALK, or ROS1 and NLR of 5.9 or higher was 4.3 months, compared to 12.1 months in patients with NLR less than 5.9 (P = .023).

Conclusions

Elevation in pretreatment NLR was associated with significantly lower overall median survival from initiation of ICI, particularly when in combination with NSCLC with alterations in EGFR, ALK, or ROS1. This finding could influence clinical practice as NLR is readily available through routine blood testing.

之前对非小细胞肺癌(NSCLC)的研究表明,具有特定驱动突变的肿瘤可能不太可能对免疫检查点抑制剂(ICI)产生反应。在这项分析中,我们评估了与无持久临床获益(NDB)的患者相比,对 ICI 有持久临床获益(DCB)的患者的特征,重点是分子改变和治疗前中性粒细胞与淋巴细胞比值(NLR)的作用。我们回顾性地收集了2015年4月至2018年5月期间斯坦福大学开始接受ICI单药治疗的晚期NSCLC患者的临床特征和预后。如果患者接受 ICI 治疗的时间大于或等于 180 天,则被归类为 DCB;如果小于 180 天,则被归类为 NDB。研究结果包括接受 ICI 治疗期间的最佳放射学疗效以及从开始接受 ICI 治疗时算起的存活率。在接受 ICI 治疗的 123 名 NSCLC 患者中,28 名患者接受了 DCB(23%)治疗,95 名患者接受了 NDB(77%)治疗。在33例发生Ⅳ或Ⅴ级分子改变且NLR大于或等于5.9的患者中,从开始接受ICI治疗起的中位总生存期为2.0个月,而发生这些基因组改变且NLR小于5.9的患者的中位总生存期为8.1个月。NLR为5.9或更高的患者的中位总生存期为4.3个月,而NLR低于5.9的患者的中位总生存期为12.1个月 ( = .023)。治疗前NLR升高与ICI起始总生存期中位数明显降低有关,尤其是与NSCLC中or发生改变的患者合并治疗时。
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引用次数: 0
期刊
Clinical lung cancer
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