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
{"title":"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","authors":"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","doi":"10.1016/j.cllc.2024.03.008","DOIUrl":"10.1016/j.cllc.2024.03.008","url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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] <em>vs.</em> 6[5-8] days, <em>P</em> = .021), reduced postoperative comorbidities (21.0% <em>vs.</em> 37.1%, <em>P</em> = .048), and dissected less N1 lymph nodes (5[4-6] <em>vs.</em> 7[5-9], <em>P</em> = .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% <em>vs.</em> 73.73%, <em>P</em> = .640), overall survival (87.22% <em>vs.</em> 88.00%, <em>P</em> = .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.</p></div><div><h3>Conclusion</h3><p>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.</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":"https://www.sciencedirect.com/science/article/pii/S1525730424000421/pdfft?md5=a8b70f17746856a06c16c8317054ee5f&pid=1-s2.0-S1525730424000421-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
{"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 , 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","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}
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
{"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":"10.1016/j.cllc.2024.06.005","url":null,"abstract":"<div><h3>Objectives</h3><div>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 <em>EGFR</em>/<em>ALK</em> 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.</div></div><div><h3>Materials and methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>Treatment-switching adjustments resulted in a greater estimated relative OS benefit with first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic NSCLC.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"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","authors":"","doi":"10.1016/j.cllc.2024.06.007","DOIUrl":"10.1016/j.cllc.2024.06.007","url":null,"abstract":"<div><h3>Introduction</h3><p>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.</p></div><div><h3>Patients and methods</h3><p>MDT-BRIDGE (NCT05925530) is a multicenter, phase II, non-randomized study in ∼140 patients with <em>EGFR</em>/<em>ALK</em> 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.</p></div><div><h3>Conclusion</h3><p>Enrollment began in February 2024; primary completion is anticipated in April 2026.</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":"https://www.sciencedirect.com/science/article/pii/S1525730424001323/pdfft?md5=8992a0869feaf0e76611fb529a5462b6&pid=1-s2.0-S1525730424001323-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141566758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"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 <T2 or >=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 >=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}
{"title":"Molecular Characteristics and Pretreatment Neutrophil-to-Lymphocyte Ratio as Predictors of Durable Clinical Benefit from Immune Checkpoint Inhibition in Non-Small Cell Lung Cancer","authors":"","doi":"10.1016/j.cllc.2024.06.006","DOIUrl":"10.1016/j.cllc.2024.06.006","url":null,"abstract":"<div><h3>Background</h3><p><span>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 </span><em>EGFR, ALK,</em> and <em>ROS1</em> and pretreatment neutrophil-to-lymphocyte ratio (NLR).</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p><span>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 </span><em>EGFR (n = 31), ALK</em>, or <em>ROS1</em> 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 <em>EGFR, ALK,</em> or <em>ROS1</em> and NLR of 5.9 or higher was 4.3 months, compared to 12.1 months in patients with NLR less than 5.9 (<em>P</em> = .023).</p></div><div><h3>Conclusions</h3><p>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 <em>EGFR, ALK,</em> or <em>ROS1.</em> This finding could influence clinical practice as NLR is readily available through routine blood testing.</p></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141577393","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}
{"title":"Gefitinib Resensitization After a TKI-Free Interval in Osimertinib Resistant Non–Small-Cell Lung Cancer: A Glimpse of Hope in Time of Crisis?","authors":"","doi":"10.1016/j.cllc.2024.06.003","DOIUrl":"10.1016/j.cllc.2024.06.003","url":null,"abstract":"<div><p></p><ul><li><span>•</span><span><p>After osimertinib<span> resistance some patients are still sensitive to EGFR blockage.</span></p></span></li><li><span>•</span><span><p>Gefitinib rechallenge seems effective after a TKI-free interval.</p></span></li><li><span>•</span><span><p><span>Liquid biopsy can track clonal evolution of </span><em>EGFR</em> mutated NSCLCs.</p></span></li><li><span>•</span><span><p>Detection of EGFR mutations on ctDNA can identify patients for this strategy.</p></span></li></ul></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141401317","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}
{"title":"The Emerging Role of Immune Checkpoint Blockade for the Treatment of Lung Cancer Brain Metastases","authors":"","doi":"10.1016/j.cllc.2024.06.004","DOIUrl":"10.1016/j.cllc.2024.06.004","url":null,"abstract":"<div><p><span>Lung cancer has the highest incidence of brain metastases (BM) among solid organ cancers. Traditionally </span>whole brain radiation therapy<span><span><span> has been utilized for non–small-cell lung cancer (NSCLC) BM treatment, although stereotactic radiosurgery<span> has emerged as the superior treatment modality for most patients. Highly penetrant central nervous system<span><span> (CNS) tyrosine kinase inhibitors have also shown significant CNS activity in patients harboring select oncogenic drivers. There is emerging evidence that patients without oncogene-driven tumors derive benefit from the use of </span>immune checkpoint inhibitors<span><span> (ICIs). The CNS activity of ICIs have not been well studied given exclusion of patients with active BM from landmark trials, due to concerns of inadequate CNS penetration and activity. However, studies have challenged the idea of an immune-privileged CNS, given the presence of functional lymphatic drainage within the CNS and destruction of the </span>blood brain barrier by BM. An emerging understanding of the interactions between tumor and CNS </span></span></span></span>immune cells<span><span> in the BM tumor microenvironment also support a role for </span>immunotherapy in BM treatment. In addition, posthoc analyses of major trials have shown improved intracranial response and survival benefit of regimens with ICIs over chemotherapy (CT) alone for patients with BM. Two prospective phase 2 trials evaluating </span></span>pembrolizumab<span><span> monotherapy and </span>atezolizumab plus CT in patients with untreated NSCLC BM also demonstrated significant intracranial responses. This review describes the interplay between CNS immune cells and tumor cells, discusses current evidence for ICI CNS activity from retrospective and prospective studies, and speculates on future directions of investigation.</span></span></p></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141406353","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}
{"title":"The Design for a Phase II, Randomized, Multicenter Study of CtDNA-Guided Treatment With Furmonertinib Combined Therapy or Furmonertinib Alone for Untreated Advanced EGFR Mutant Non–small-cell Lung Cancer Patients: The FOCUS-C Study","authors":"","doi":"10.1016/j.cllc.2024.06.002","DOIUrl":"10.1016/j.cllc.2024.06.002","url":null,"abstract":"<div><h3>Background</h3><div><span>Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have significant </span>antitumor activity<span> to advanced non–small-cell lung cancer (NSCLC) patients with classic EGFR<span> mutations. However, EGFR-TKI monotherapy shows poor efficacy in patients whose circulating tumor cell DNA (ctDNA) of EGFR mutations cannot be rapidly cleared.</span></span></div></div><div><h3>Materials and Methods</h3><div><span>As a third-generation TKI, furmonertinib has shown superior antitumor activity and minor toxicity. The FOCUS-C study is a prospective, multicenter, randomized controlled trial (NCT05334277) to explore the efficacy and safety of furmonertinib plus pemetrexed-platinum doublet chemotherapy with or without </span>bevacizumab<span><span> versus furmonertinib monotherapy in untreated advanced EGFR mutant NSCLC patients without EGFR clearance after the induction therapy of furmonertinib. Patients with EGFR clearance will still receive furmonertinib as Arm A. Patients without ctDNA clearance will be randomized in a 2:2:1 ratio as Arm B1 (furmonertinib), Arm B2 (furmonertinib combined with carboplatin<span> and pemetrexed for 4 cycles, and then furmonertinib and pemetrexed as maintenance therapy) and Arm B3 (Arm B2 regimen plus bevacizumab). The primary endpoint is progression-free survival (PFS) in Arm B2/B1. Secondary endpoints include PFS in Arm B3/B1, PFS in Arm A/B1, PFS in Arm B3/B2, objective response and disease control rate, </span></span>overall survival and safety in all Arms. Exploratory endpoints are focused on the efficacy based on plasma NGS at different timepoints.</span></div></div><div><h3>Conclusion</h3><div>This study will evaluate the efficacy and tolerability of furmonertinib plus carboplatin and pemetrexed with or without bevacizumab verses furmonertinib alone in untreated patients with advanced EGFR mutant NSCLC without EGFR clearance.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141399561","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}
{"title":"Surgery and Stereotactic Radiotherapy for Stage I Small-Cell Lung Carcinoma: A 25-Year Experience","authors":"","doi":"10.1016/j.cllc.2024.06.001","DOIUrl":"10.1016/j.cllc.2024.06.001","url":null,"abstract":"<div><h3>Objectives</h3><p>Small-cell lung carcinoma (SCLC) is usually a wide-spread, highly-lethal malignancy but occasionally presents as localized, limited stage cancer amenable to local treatment. We reviewed our experience using surgery or stereotactic body radiotherapy (SBRT) to assess safety, survival rates and treatment toxicity in clinical stage I SCLC patients.</p></div><div><h3>Materials and Methods</h3><p>Electronic medical records of patients with clinical stage I lymph node-negative SCLC who underwent surgical resection or SBRT between 1996 and 2021 were retrospectively reviewed. A multivariable Cox Proportional Hazards model was constructed.</p></div><div><h3>Results</h3><p>Of 96 patients meeting inclusion criteria, 77 underwent resection and 19 underwent SBRT. Surgical patients were younger (mean 68.4 ± 9.2 years surgery versus 74.3 ± 6.6 years SBRT, <em>P</em> = .005) and had better pulmonary function (81.5 ± 19.6 FEV1% of predicted surgery versus 44.0 ± 20.9% SBRT, <em>P</em> < .001). SBRT patients had significantly more comorbidities. For both cohorts, 59 tumors were pure SCLC and 37 were mixed SCLC/NSCLC histology. Median survivals were 21 months versus 31 months for SBRT and surgery patients respectively (<em>P</em> = .07). There were no treatment-related mortalities. Mean length of hospital stay for surgical patients was 5.4 ± 5.7 days. Survival was longer in lymph node-negative surgery patients (median 48 months node-negative versus 19 months node-positive, <em>P</em> = .04). For node-negative-surgery patients, the estimated 2- and 5-year survival rates are 60% and 48%.</p></div><div><h3>Conclusions</h3><p>Our single-institutional experience over 25 years demonstrates that local treatment with surgery or SBRT for clinical stage I SCLC is safe and effective, with survivals lower than similar stage non–small-cell carcinoma patients. However, our results compare favorably with prior small-cell surgical series and far better than reported results of chemoradiotherapy for similar stage patients, thereby validating current recommendations for employing surgery or SBRT for stage I SCLC.</p></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525730424001104/pdfft?md5=2719331e3ee9daf272c5902b07058ecd&pid=1-s2.0-S1525730424001104-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141405878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}