Clinical lung cancer最新文献

{"title":"Statin Use With Immune Checkpoint Inhibitors and Survival in Nonsmall Cell Lung Cancer.","authors":"Michael T Marrone, Joshua E Reuss, Anna Crawford, Brian Neelon, Jun O Liu, Julie R Brahmer, Elizabeth A Platz","doi":"10.1016/j.cllc.2024.12.008","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.12.008","url":null,"abstract":"<p><strong>Objective: </strong>To determine the association between concurrent statin use with immune checkpoint inhibitors (ICIs) and lung cancer-specific and overall mortality in patients with nonsmall cell lung cancer (NSCLC).</p><p><strong>Materials and methods: </strong>SEER-Medicare was used to conduct a retrospective study of Medicare beneficiaries ≥65 years of age diagnosed with NSCLC between 2007 and 2017 treated with an ICI. Patients were followed from date of first ICI claim until death, 1 month from last ICI claim, or 12/31/2018, whichever came first. Associations for time-updated statin use and lung cancer-specific mortality, and overall mortality were estimated using Cox models adjusted for demographic, pathological, treatment-related factors, and a propensity score for statin use.</p><p><strong>Results: </strong>Among 1,401 patients, concurrent statin use with any ICI was associated with 41% lower risk of lung-cancer specific mortality compared to patients receiving ICI not using a statin (HR = 0.59; 95% CI = 0.35-0.99). Statin use was associated with a similarly lower risk of overall mortality (HR = 0.62; 95% CI = 0.41-0.94). Consistent inverse associations were observed when restricting to PD-1 inhibitors and by statin type. Limited anti-PD-L1 treatment prevented analysis in this subgroup.</p><p><strong>Conclusion: </strong>Concurrent statin use with ICIs was associated with lower risk of lung cancer-specific and overall mortality in a population-based sample of older patients with NSCLC. Future work is needed to confirm these findings in prospective studies and randomized trials, including evaluating concurrent statin use with frontline ICIs, deciphering the underlying mechanism, and determining the optimal statin-ICI combination that maximize clinical benefit.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001372","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":"Adjuvant Chemotherapy Decisions in the Treatment of Lung Cancer Considering Nonrelapse Mortality: A Multicenter Study.","authors":"Mitsue Kawahara, Yosuke Matsuura, Shota Nakamura, Fumie Kinoshita, Keiju Aokage, Tetsuhiko Asao, Toyofumi Fengshi Chen-Yoshikawa, Mingyon Mun","doi":"10.1016/j.cllc.2024.12.009","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.12.009","url":null,"abstract":"<p><strong>Background: </strong>Adjuvant chemotherapy (Adj) reduces recurrence and improves long-term survival in patients with surgically resected lung cancer. However, it has minimal impact on patients who die without relapsing. To optimize Adj indications, we aimed to identify factors associated with nonrelapse mortality (NRM).</p><p><strong>Patients and methods: </strong>This multicenter, retrospective, observational study enrolled patients with surgically resected with stages II-III non-small cell lung cancer. Multivariable Cox regression analysis was performed to identify the factors associated with NRM and early-NRM within 2 years of surgery and to stratify the enrolled patients. Adj administration rates and postoperative overall and recurrence-free survival rates were compared. Multivariable competing regression analysis with NRM as a competing risk was used to assess the cumulative incidence of lung cancer-associated death and recurrence.</p><p><strong>Results: </strong>Through a scoring system assigning 1 point to each extracted factor (old age, male sex, poor performance status, nonadenocarcinoma, and occurrence of major complications), the 1,244 included patients were stratified into 3 groups based on scores of 0-5: A (0-1 points; n = 613), B (2-3 points; n = 549), and C (4-5 points; n = 62) with 53%, 26%, and 11% Adj administration, respectively. Although group A showed the highest overall and recurrence-free survival rates, competing regression analysis showed no significant differences in cumulative lung cancer-associated death and recurrence incidence between the groups.</p><p><strong>Conclusion: </strong>Better prognosis in group A was attributed to lower NRM and higher Adj administration rates. While proactive Adj may benefit group A, careful evaluation is warranted for group C to optimize Adj indication.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001312","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":"Association of Immune-Related Adverse Events With Efficacy in Consolidation Nivolumab Plus Ipilimumab or Nivolumab Alone After Chemoradiation in Patients With Unresectable Stage III Nonsmall Cell Lung Cancer: An Exploratory Analysis From the Big 10 Cancer Research Consortium Study BTCRC LUN 16-081.","authors":"Cynthia X Wei, Sandra K Althouse, Hirva Mamdani, Nasser H Hanna, Greg A Durm","doi":"10.1016/j.cllc.2024.12.007","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.12.007","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy has been widely incorporated into the treatment of patients with non-small-cell lung cancer (NSCLC). Many of these patients will experience immune-related adverse events (irAEs) without decreased efficacy. We report a retrospective analysis of the association between irAEs and efficacy outcomes from the BTCRC LUN 16-081 randomized phase 2 trial of consolidation nivolumab (N) plus ipilimumab (IPI) vs N alone following chemoradiotherapy in unresectable Stage IIIA/IIIB NSCLC.</p><p><strong>Results: </strong>A total of 105 patients enrolled from 9/2017 to 4/2021. In arm A (N alone), 65 % of patients developed irAEs with no difference in PFS or OS in patients with and without irAEs. In arm B (IPI+N), 84 % of patients developed irAE with no difference in OS in patients with and without irAEs, but longer PFS in those who experienced irAEs (30.9 vs. 6.8mo, P = .010). Patients in Arm A that discontinued treatment due to irAE (n = 8) had shorter PFS (8.2 vs. 31.9mo, P ≤ .0001) and OS (12.3mo vs. NE, P < .0001). Patients in Arm B that discontinued treatment due to irAEs (n = 18) had no difference in either PFS or OS.</p><p><strong>Conclusions: </strong>The development of irAEs after chemoradiotherapy due to the use of Nivolumab alone or in combination with Ipilimumab did not result in reduced efficacy outcomes, with an observed improvement in PFS in the combination arm. If the irAEs resulted in discontinuation of treatment, this was associated with decreased efficacy outcomes in the N alone arm but not in the IPI + N arm.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001317","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":"Tarlatamab Rechallenge After Grade 3 Cytokine Release Syndrome Leading to Tumor Regression in Two Weeks and Reopening of a Collapsed Lung: A Case Report","authors":"Timothy Schieber,&nbsp;Prakash Neupane,&nbsp;Haoran Li,&nbsp;Chao Huang,&nbsp;Jun Zhang","doi":"10.1016/j.cllc.2024.12.005","DOIUrl":"10.1016/j.cllc.2024.12.005","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Tarlatamab's onset of tumor regression can be as short as 2 weeks.</div></span></li><li><span>•</span><span><div>Rechallenging tarlatamab after grade 3 CRS with standard premedication is safe.</div></span></li><li><span>•</span><span><div>Tarlatamab combined with IMRT offers safe and highly effective CNS control.</div></span></li><li><span>•</span><span><div>A collapsed lung from tumor burden may re-expand with tarlatamab monotherapy.</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 2","pages":"Pages e126-e129"},"PeriodicalIF":3.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930638","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":"Brief Report: Osimertinib Plus Capmatinib for Patients With MET-Altered EGFR-Mutant NSCLC Following Progression on Front Line Therapy","authors":"Omar Elghawy,&nbsp;Adam Barsouk,&nbsp;Lauren Reed-Guy,&nbsp;Margaret Stalker,&nbsp;Jonathan Sussman,&nbsp;Kyle Robinson,&nbsp;John Kosteva,&nbsp;Aditi Singh,&nbsp;Roger B. Cohen,&nbsp;Corey Langer,&nbsp;Christine Ciunci,&nbsp;Christopher D'Avella,&nbsp;Lova Sun,&nbsp;Melina E. Marmarelis,&nbsp;Charu Aggarwal","doi":"10.1016/j.cllc.2024.11.014","DOIUrl":"10.1016/j.cllc.2024.11.014","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Osimertinib, a third generation EGFR TKI, has become the standard-of-care treatment for patients with classical sensitizing EGFR mutations and has significantly improved survival in these patients.</div></span></li><li><span>•</span><span><div>Alterations in the MET tyrosine kinase pathway is one of the most common drivers of resistance to EGFR TKIs.</div></span></li><li><span>•</span><span><div>Multiple early-phase studies have investigated dual EGFR/MET inhibition for EGFR mutant patients with MET amplification in the second-line setting after progression on osimertinib however real world data is limited.</div></span></li><li><span>•</span><span><div>We report a case series of 18 patients with MET amplification/overexpression treated with combination capmatinib/osimertinib after progression of first line osimertinib.</div></span></li><li><span>•</span><span><div>Most patients with combination capmatinib and osimertinib had clinical benefit and treatment was generally well tolerated.</div></span></li><li><span>•</span><span><div>Cap/osi is an effective and reasonably well tolerated treatment for osimertinib-resistant EGFR-mutant NSCLC with MET alteration. Further work is needed to optimize biomarker assessment to appropriately identify patients who will benefit from this strategy.</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 2","pages":"Pages 158-163.e2"},"PeriodicalIF":3.3,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913992","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":"Neratinib Efficacy in Patients With EGFR Exon 18-Mutant Non-Small-Cell Lung Cancer: Findings From the SUMMIT Basket Trial.","authors":"Jonathan W Goldman, Alejandro Martinez Bueno, Christophe Dooms, Komal Jhaveri, Maria de Miguel, Sarina A Piha-Paul, Nisha Unni, Aviad Zick, Amit Mahipal, J Marie Suga, Charles Naltet, Monica Antoñanzas, John Crown, Judith Bebchuk, Lisa D Eli, Beth H Lowenthal, Devalingam Mahalingam","doi":"10.1016/j.cllc.2024.12.003","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.12.003","url":null,"abstract":"<p><strong>Background: </strong>Activating mutations in the epidermal growth factor receptor (EGFR) gene occur in 7% to 23% of patients with non-small-cell lung cancer (NSCLC). A small proportion of these (3-5%) are exon 18 mutations. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), had activity in the phase II SUMMIT basket study. We report efficacy and safety of neratinib in patients with EGFR exon 18-mutant NSCLC in SUMMIT, according to prior EGFR TKI treatment.</p><p><strong>Patients and methods: </strong>Eligible patients had ECOG performance status 0-2. Prior EGFR TKIs, chemotherapy, and checkpoint inhibitors were allowed. Patients received neratinib (240 mg orally daily) and mandatory diarrhea prophylaxis with loperamide. The primary endpoint was objective response rate (ORR) at 8 weeks (ORR₈); other endpoints included ORR, progression-free survival (PFS), duration of response, and safety.</p><p><strong>Results: </strong>Thirty-one patients were included (24/7 with/without prior TKI). ORR₈ was 19.4% (95% CI 7.5-37.5); ORR was 32.3% (95% CI: 16.7-51.4); median PFS 5.75 months (95% CI: 2.27-9.23). Two of 7 patients with baseline central nervous system metastasis had partial responses (median PFS 3.6 months; 95% CI: 1.9-9.1). Six patients with G719A/X/C mutations had partial responses >10 months. Diarrhea was generally controlled (10% grade 3, no grade 4; one patient discontinued treatment because of diarrhea).</p><p><strong>Conclusion: </strong>Neratinib had meaningful activity in selected patients with EGFR exon 18-mutant NSCLC, including patients pretreated with ≥1 TKI. Diarrhea was generally low grade. Given the lack of effective treatments after EGFR TKI failure for NSCLC with uncommon mutations, further examination of neratinib is warranted.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001329","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":"A Phase II, Open Label, Single-Arm Study on the Efficacy of Cabozantinib in Patients With Advanced/Metastatic Nonsmall Cell Lung Cancer Harboring MET Exon 14 Alterations who Developed Acquired Resistance to Tepotinib or Capmatinib (CAPTURE Trial).","authors":"Masayuki Takeda, Masahide Ota, Eiji Iwama, Shunichi Sugawara, Takehito Shukuya, Shigeki Umemura, Hiroshi Tanaka, Masahide Oki, Takayuki Takahama, Takeshi Masuda, Naoyuki Nogami, Mototsugu Shimokawa","doi":"10.1016/j.cllc.2024.12.004","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.12.004","url":null,"abstract":"<p><strong>Background: </strong>MET gene exon 14 skipping was identified as a potential driver mutation that occurs in approximately 3%-4% of patients with nonsmall cell lung cancer (NSCLC), typically in the absence of other driver mutations. Capmatinib and tepotinib were the first MET- tyrosine kinase inhibitors (MET-TKIs) approved by the FDA and PMDA, specifically for patients with metastatic NSCLC. Several studies have reported acquired resistance after MET-TKI treatment for MET mutation-positive NSCLC. Sequencing of the MET kinase region of resistant cell lines revealed secondary mutations at residues D1228 and Y1230 that were sensitive to type II MET-TKIs, such as cabozantinib. This suggested that sequential administration of other MET-TKIs may overcome the development of secondary mutations after acquired resistance in MET exon 14 mutation-positive NSCLC.</p><p><strong>Methods: </strong>We designed the single arm phase II study CAPTURE Trial to assess the efficacy of cabozantinib in patients with advanced/metastatic NSCLC with activating MET exon 14 alterations who developed acquired resistance to tepotinib or capmatinib, as well as after 2 prior chemotherapy regimens that included platinum and docetaxel. The primary endpoint was objective response rate by independent review committees. The sample size (n = 30) is calculated by assuming a threshold response rate of 5% and an expected response rate of 25%. Recruitment began in August 2024.</p><p><strong>Results: </strong>This ongoing study aimed to evaluate the safety and efficacy of cabozantinib after acquired resistance to tepotinib or capmatinib.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913989","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":"Computer Assisted Nodule Analysis and Risk Yield is Associated With Occult Lymph Node Status in Clinical Stage I-IIA Lung Adenocarcinoma Undergoing Resection.","authors":"Duy Pham, Ju Ae Park, Hongkun Wang, Melanie Subramanian, Michael J Weyant, Kei Suzuki","doi":"10.1016/j.cllc.2024.11.013","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.11.013","url":null,"abstract":"<p><strong>Background: </strong>Current staging work-up does not capture all occult lymph node (OLN) disease. We sought to determine if Computer Assisted Nodule Analysis and Risk Yield (CANARY) analysis could help distinguish OLN status in early-stage lung adenocarcinoma.</p><p><strong>Methods: </strong>Retrospective review of resected lung cancer patients from 2016 to 2021 was performed. Patients with surgically resected clinical stage I-IIA lung adenocarcinoma were included. Preoperative imaging was entered into the CANARY software, and each lesion was categorized into good, intermediate, and poor risk. OLN status was determined per pathology results. Pearson's Chi-square correlation, univariate and multivariate logistic regression models were used to assess OLN metastases as a function of CANARY risk profile, with statistical significance at α=0.05.</p><p><strong>Results: </strong>In total, the study cohort included 228 patients with median age of 70. By clinical stage, 195 (85.5%), 24 (10.5%), and 9 (3.9%) patients were determined to be in IA, IB, and IIA, respectively. 28 (12.3%) patients were found to have OLN metastases. Among them, 1 (3.6%), 3 (10.7%), and 24 (85.7%) patients had a good, intermediate, and poor CANARY risk profile, respectively. CANARY risk profile was significantly associated with OLN metastases (χ2 = 9.9, P = .007). Relative to the good/intermediate group, patients with poor risk had a more-than 3-fold increase in likelihood of having OLN metastases (odd ratio [OR] = 3.3, 95% confidence interval [CI]:1.6-9.2, P = .007).</p><p><strong>Conclusion: </strong>CANARY analysis was able to risk-stratify the likelihood of OLN metastases in early-stage lung adenocarcinoma. CANARY can provide an adjunctive non-invasive tool to aid in determining an appropriate individualized treatment plan.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885250","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":"Phase II Parallel Arm Study of Sacituzumab Govitecan-Hziy in Patients With Advanced Thymoma or Thymic Carcinoma.","authors":"Jennifer A Marks, Jaeil Ahn, Joshua E Reuss, David Barbie, Mehmet Altan, Martin E Gutierrez, Marina C Garassino, Gregory J Riely, Heather Wakelee, Stephen V Liu, Chul Kim","doi":"10.1016/j.cllc.2024.12.001","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.12.001","url":null,"abstract":"<p><strong>Background: </strong>Thymic epithelial tumors (TETs), including thymoma and thymic carcinoma, are rare thoracic tumors of the anterior mediastinum. For those with advanced disease, platinum-based chemotherapy is used as first-line treatment. However, there is no standard regimen established for TET at progression after initial therapy, and treatment options for advanced/recurrent TETs are limited. Trop-2, a transmembrane glycoprotein, is overexpressed in solid tumors including thymomas and thymic carcinomas. Sacituzumab govitecan-hziy, a Trop-2-directed antibody-drug conjugate, has shown efficacy and safety in several tumors including breast cancer. The overexpression of Trop-2 in TETs and the clinical efficacy in other malignancies provide rationale for exploring its use in thymoma and thymic carcinoma.</p><p><strong>Methods: </strong>This open-label, single-arm, parallel cohort, multi-center study assesses the safety and efficacy of sacituzumab govitecan-hziy in patients with advanced thymoma (cohort A) and thymic carcinoma (cohort B) who have received at least 1 prior line of systemic therapy (NCT06248515). The study employs a Simon optimal 2-stage design, enrolling patients with adequate performance status, measurable disease, and adequate organ function. Sacituzumab govitecan-hziy is administered at a fixed dose of 10 mg/kg weekly on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Follow-up continues every 6 months for 2 years postdiscontinuation. Archival tissue is obtained prior to initiation of study treatment with an optional biopsy at the time of progression. In cases where archival tissue is not available, a fresh biopsy is obtained at baseline. The primary endpoint is investigator-assessed response rate using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST) criteria, with tumor imaging assessments every 2 cycles during the first 3 months and every 3 cycles thereafter. Secondary endpoints comprise adverse events by Common Terminology Criteria for Adverse Events v5.0, median and 6-month progression-free survival, duration of response, and overall survival. For each cohort, 9 patients will be enrolled. If 0 of the 9 achieve a response, no further patients will be enrolled in that cohort. If 1 or more of the first 9 patients has a response, accrual will continue until a total of 17 patients have been enrolled in that cohort.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926593","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":"PEARL: A Multicenter Phase 2 Study of Lorlatinib in Patients with ALK-Rearranged NSCLC and Central Nervous System Disease.","authors":"Chang Lu, Hong-Hong Yan, Chan-Yuan Zhang, Shi-Yuan Chen, Yang-Si Li, Bin-Chao Wang, Chong-Rui Xu, Hai-Yan Tu, Wen-Zhao Zhong, Qing Zhou, Xu-Chao Zhang, Yi-Long Wu, Wei-Neng Feng, Guan-Ming Jiang, Jin-Ji Yang","doi":"10.1016/j.cllc.2024.12.002","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.12.002","url":null,"abstract":"<p><strong>Background: </strong>Patients with ALK-rearranged non-small cell lung cancer (ALK+ NSCLC) with symptomatic brain (BM) and leptomeningeal (LM) metastases are underrepresented in clinical trials due to poor performance status. Additionally, the need for improved and validated assessment criteria for evaluating central nervous system (CNS) response remains critical. Lorlatinib has demonstrated systemic activity in patients with ALK+ NSCLC. This ongoing phase II study aims to evaluate the efficacy and safety of lorlatinib in ALK+ NSCLC patients with progressive CNS metastases.</p><p><strong>Patients and methods: </strong>This study is a multicenter, open-label, single-arm, prospective trial. Fifty eligible subjects will be divided into 2 cohorts: BM (progressive or new brain parenchymal; n = 30) and LM (positive cerebrospinal fluid cytology and/or MRI ± brain parenchymal metastasis; n = 20). Key inclusion criteria include ALK status confirmed using FDA-approved tests, at least 1 CNS lesion, with or without CNS-related symptoms, and an ECOG performance status of 0-2 for the BM cohort and 0-3 for the LM cohort. Primary endpoint is intracranial objective response rate based on the modified version of response evaluation criteria in solid tumors v1.1 for BM and modified RANO-LM criteria for LM. Key secondary endpoints include intracranial progression-free survival, overall progression-free survival, objective response rate, overall survival, safety and quality of life. Biomarker analysis of paired pretreatment tumor, blood and optional cerebrospinal fluid will be performed as preplanned exploratory analyses.</p><p><strong>Conclusions: </strong>The PEARL study (CTONG2303) will evaluate efficacy of lorlatinib in CNS metastases in ALK+ NSCLC using refined CNS response evaluation criteria, with biomarker analyses providing insights into response and resistance mechanisms.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892661","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}