Lung Cancer最新文献

{"title":"Efficacy and safety of pralsetinib in patients with RET fusion positive non–small cell lung cancer: An observational real world study","authors":"Dehua Liao ,&nbsp;Minghui Long ,&nbsp;Jiwen Zhang ,&nbsp;Xingyu Wei ,&nbsp;Fei Li ,&nbsp;Ting Yan ,&nbsp;Desong Yang","doi":"10.1016/j.lungcan.2024.107936","DOIUrl":"10.1016/j.lungcan.2024.107936","url":null,"abstract":"<div><h3>Background</h3><p>Pralsetinib, a selective <em>RET</em> targeted tyrosine kinase inhibitor (TKI), has been approved for treating locally advanced or metastatic <em>RET</em> fusion-positive NSCLC in adults who have previously received platinum-based chemotherapy in China.</p></div><div><h3>Methods</h3><p>In this retrospective analysis conducted at Hunan Cancer Hospital in China, we examined 36 patients with advanced NSCLC with <em>RET</em> fusion, who were treated with pralsetinib between January 2021 and December 2023. The study focused on assessing the efficacy (Progression-free survival (PFS) and overall survival (OS)) and safety profile of pralsetinib in these patients. Statistical analyses were conducted using SPSS version 20.0, with a significance level set at p &lt; 0.05.</p></div><div><h3>Results</h3><p>The results revealed that pralsetinib exhibited significant activity in this patient cohort. Kaplan-Meier survival analysis indicated a median PFS of 10.7 months and a median OS of 21.2 months. The overall response rate<!--> <!-->(ORR) and disease control rate (DCR) was 55.6 % and 72.2 %, respectively. Pralsetinib was generally well tolerated, with most adverse events being mild to moderate (grades 1–2). The most common serious adverse events (≥grade 3) observed were lymphopenia (13.9 %), hypertension (11.1 %), leukopenia (8.3 %), neutropenia (8.3 %), and creatine kinase elevation (8.3 %).</p></div><div><h3>Conclusion</h3><p>Pralsetinib demonstrated promising activity in patients with advanced NSCLC harboring <em>RET</em> fusion with a favorable safety profile.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107936"},"PeriodicalIF":4.5,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169500224004707/pdfft?md5=1018d4da08ed33bf4bf2bcc119b7a419&pid=1-s2.0-S0169500224004707-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Capmatinib efficacy for METex14 non-small cell lung cancer patients: Results of the IFCT-2104 CAPMATU study","authors":"Marion Ferreira ,&nbsp;Aurélie Swalduz ,&nbsp;Laurent Greillier ,&nbsp;Pauline du Rusquec ,&nbsp;Hubert Curcio ,&nbsp;Judith Raimbourg ,&nbsp;Anne-Claire Toffart ,&nbsp;Valérie Gounant ,&nbsp;Sebastien Couraud ,&nbsp;Gonzague De Chabot ,&nbsp;Sylvie Friard ,&nbsp;José Hureaux ,&nbsp;Gaëlle Jeannin ,&nbsp;Luc Odier ,&nbsp;Charles Ricordel ,&nbsp;Marie Wislez ,&nbsp;Clotilde Descarpentries ,&nbsp;Guillaume Herbreteau ,&nbsp;Pascale Missy ,&nbsp;Franck Morin ,&nbsp;Alexis B. Cortot","doi":"10.1016/j.lungcan.2024.107934","DOIUrl":"10.1016/j.lungcan.2024.107934","url":null,"abstract":"<div><h3>Background</h3><p>Capmatinib is a selective MET inhibitor with demonstrated efficacy in a phase II study of non-small cell lung cancer (NSCLC) patients harboring <em>MET</em>ex14 mutations. However, the real-world outcomes of capmatinib are largely unknown. From June 2019, the French Early Access Program (EAP) provided capmatinib to <em>MET</em>ex14 NSCLC patients who were ineligible for or for whom first-line standard therapies had failed.</p></div><div><h3>Methods</h3><p>IFCT-2104 CAPMATU was a multicenter study that included all <em>MET</em>ex14 NSCLC patients who received capmatinib as part of the EAP until August 2021. The primary endpoints were time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS) and objective response rate (ORR).</p></div><div><h3>Results</h3><p>A total of 146 patients were included. The median age was 74.9 years, 56.6 % were never-smokers, and 32.4 % had brain metastases. The median TTF, median PFS and median OS from capmatinib initiation were 5.1 months (95 % CI 4.2–6.0), 4.8 months (95 % CI 4.0–6.0) and 10.4 months (95 % CI 8.3–13.2), respectively. Evaluation of the best response to capmatinib was available for 134 patients and resulted in an ORR of 55.3 % (95 % CI 46.8 %-63.6 %). The median PFS was 7.7 months for treatment-naïve patients and 6.0 and 4.1 months for patients who had received one or 2 + prior lines of treatment, respectively. For patients with brain metastases, the median PFS was 3.0 months. Capmatinib had a known and manageable safety profile, with grade 3 to 4 adverse events, mostly peripheral edema (8.2 %), occurring in 17.8 % of patients.</p></div><div><h3>Conclusion</h3><p>In this large real-world study of <em>MET</em>ex14 NSCLC patients, the efficacy of capmatinib was confirmed, with a manageable safety profile, even in patients with brain metastases and in those who received several lines of treatment. This study reinforces the key role of capmatinib for these patients.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107934"},"PeriodicalIF":4.5,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor immune microenvironment of NSCLC with EGFR exon 20 insertions may predict efficacy of first-line ICI-combined regimen","authors":"Ke-Jun Liu ,&nbsp;Hong-Rui Li ,&nbsp;Quan-Quan Tan ,&nbsp;Tao Jiang ,&nbsp;Kai-Cheng Peng ,&nbsp;Hua-Jun Chen ,&nbsp;Qing Zhou ,&nbsp;Xu-Chao Zhang ,&nbsp;Zheng Zheng ,&nbsp;Shi-Yuan Chen ,&nbsp;Xue Zheng ,&nbsp;Hong-Bo Zheng ,&nbsp;Bei-Bei Mao ,&nbsp;Long-Long Gong ,&nbsp;Xian-Wen Chen ,&nbsp;Wendy Wu ,&nbsp;Yi-Long Wu ,&nbsp;Jun Jia ,&nbsp;Jin-Ji Yang","doi":"10.1016/j.lungcan.2024.107933","DOIUrl":"10.1016/j.lungcan.2024.107933","url":null,"abstract":"<div><h3>Objectives</h3><p>Non–small cell lung cancer (NSCLC) patients with exon 20 insertion mutations (ex20ins) of the epidermal growth factor receptor (<em>EGFR</em>) were resistant to monotherapy of immune checkpoint inhibitor (ICI). However, recent reports have shown that the combination of ICI and chemotherapy (ICI-combined regimen) exhibited certain efficacy for NSCLC with <em>EGFR</em> ex20ins. The mechanisms behind this phenomenon have not been thoroughly clarified. Hence, we conducted this study to<!--> <!-->find correlations between the tumor immune microenvironment of <em>EGFR</em> ex20ins and the efficacy of ICI-combined regimen.</p></div><div><h3>Methods</h3><p>We performed single-cell transcriptome sequencing and multiplex immunofluorescence staining (mIF) to investigate the immune microenvironment of NSCLC patients with <em>EGFR</em> ex20ins, L858R, and <em>EGFR</em> wild-type. We analyzed 15 treatment-naïve NSCLC samples utilizing single-cell RNA sequencing (scRNA-seq). Another 30 cases of <em>EGFR</em> L858R and 4 cases of wild-type were recruited to compare the immune microenvironment with that of <em>EGFR</em> ex20ins (28 cases) by mIF.</p></div><div><h3>Results</h3><p>We observed that cell components, function and interactions varied between <em>EGFR</em> ex20ins, L858R, and wild-type NSCLC.<!--> <!-->We discovered similar T cell and CD8+ T cell distributions among groups but found noninferior or even better T cell activation in ex20ins patients. Infiltrating CD8+ FOXP3- T cells were significantly lower in the tumor region of <em>EGFR</em> ex20ins compared to wild-type. T cells from the ex20ins group had a greater tendency to promote cancer cell inflammation and epithelial-mesenchymal transition (EMT) compared to wild-type group. For macrophages, there were more M2-like macrophages in ex20ins patients. M1-like macrophages in ex20ins group produced fewer antitumor cytokines than in other groups.</p></div><div><h3>Conclusions</h3><p>The immune microenvironment of <em>EGFR</em> ex20ins is more suppressive than that of L858R and wild-type, suggesting that ICI monotherapy may not be sufficient for these patients. ICI-combined regimen might be a treatment option for <em>EGFR</em> ex20ins due to tumor-promoting inflammation and noninferior T cell functions in the immune microenvironment.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107933"},"PeriodicalIF":4.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169500224004677/pdfft?md5=6550cbad2391f75000eae6f38f17ac39&pid=1-s2.0-S0169500224004677-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase I/II trial of plinabulin in combination with nivolumab and ipilimumab in patients with recurrent small cell lung cancer (SCLC): Big ten cancer research consortium (BTCRC-LUN17-127) study","authors":"Jyoti Malhotra ,&nbsp;Alberto Chiappori ,&nbsp;Naomi Fujioka ,&nbsp;Nasser H. Hanna ,&nbsp;Lawrence E. Feldman ,&nbsp;Malini Patel ,&nbsp;Dirk Moore ,&nbsp;Chunxia Chen ,&nbsp;Salma K. Jabbour","doi":"10.1016/j.lungcan.2024.107932","DOIUrl":"10.1016/j.lungcan.2024.107932","url":null,"abstract":"<div><h3>Background</h3><p>Plinabulin is a GEF-H1 releasing agent with an immune-enhancing function. We report results from a multicenter Phase I/II study (NCT03575793) assessing plinabulin in combination with nivolumab and ipilimumab for the treatment of recurrent SCLC.</p></div><div><h3>Methods</h3><p>In Phase I, patients were enrolled using a 3 + 3 design to determine dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D). Patients received nivolumab (1 mg/kg), ipilimumab (3 mg/kg), and plinabulin (in escalating doses) on day 1 of each 21-day cycle for 4 cycles followed by maintenance with plinabulin and nivolumab. In phase II, patients with recurrent PD(L)1 inhibitor resistant SCLC were enrolled. The primary objective was median progression-free survival (PFS).</p></div><div><h3>Results</h3><p>Between 9/2018 and 2/2023, 39 patients were enrolled, and 36 patients received study treatment and were evaluable for safety (16 in Phase I; 20 in Phase II). In the phase I dose-escalation, there were 2 DLTs; grade 3 altered mental status lasting &lt;24 h and grade 3 infusion reaction. The Plinabulin RP2D was determined to be 30 mg/m². Common TRAEs were vomiting (44 %), nausea (42 %), and infusion reaction (36 %); 6 % of patients had a ≥grade 3 TRAE. Five patients (14 %) had ≥grade 3 irAEs; there were no cases of immune-related pneumonitis. In the efficacy analysis in 27 patients, the median PFS was 1.6 months (95 % CI 1.2 to 2.7) and the trial did not meet the pre-specified target median PFS of 3.5 months. Four patients treated at 30 mg/m² had PR (confirmed 1, unconfirmed 3); 5 patients had SD with a CBR of 33 %. Two of 8 patients treated in phase I at the lower 20 mg/m² dose had confirmed PR, with 1 patient on the drug regimen for &gt;90 cycles. The median OS and follow-up time were 5.5 months and 2.5 months respectively.</p></div><div><h3>Conclusions</h3><p>Plinabulin in combination with nivolumab and ipilimumab was tolerable at the dose of 30 mg/m². While the clinical responses in PD-1 resistant SCLC were limited, some patients had a long duration of response. The number of ≥grade 3 irAE with the combination were lower than expected.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107932"},"PeriodicalIF":4.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142020797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long term outcomes after lobar versus sublobar resection for patients with Non-Small cell lung Cancer: Systematic review and individual patient data Meta-Analysis","authors":"Panagiotis Tasoudis ,&nbsp;Georgios Loufopoulos ,&nbsp;Vasiliki Manaki ,&nbsp;Mitchell Doerr ,&nbsp;Chris B. Agala ,&nbsp;Jason M. Long ,&nbsp;Benjamin E. Haithcock","doi":"10.1016/j.lungcan.2024.107929","DOIUrl":"10.1016/j.lungcan.2024.107929","url":null,"abstract":"<div><h3>Objectives</h3><p>Surgical resection remains the primary treatment for early-stage non-small cell lung cancer (NSCLC), with lobectomy considered the standard approach. However, recent evidence suggests that sublobar resection may be an alternative option for select patients.</p></div><div><h3>Materials and Methods</h3><p>A systematic review and <em>meta</em>-analysis were conducted following PRISMA guidelines. Randomized controlled trials (RCTs) and propensity-score matched (PSM) cohort studies comparing lobectomy and sublobar resection in NSCLC patients were included. The primary outcome was overall survival (OS), and secondary outcomes included disease-free survival (DFS), 30-day mortality, and cancer recurrence rates. Individual patient data (IPD) were reconstructed from Kaplan-Meier curves, and one-stage and two-stage <em>meta</em>-analyses were performed.</p></div><div><h3>Results</h3><p>A total of 18 studies involving 6,075 NSCLC patients (3,119 undergoing lobectomy, 2,956 undergoing sublobar resection) were included. Lobectomy was associated with significantly better OS compared to sublobar resection (hazard ratio [HR]: 0.78, 95 % confidence interval [CI]: 0.68–0.89, p &lt; 0.001). However, when sublobar resection was further divided into segmentectomy and wedge resection, no significant difference in OS was observed between lobectomy and segmentectomy (HR:0.92, 95 %CI: 0.75–1.14, p = 0.464) whereas lobar resection was associated with better OS compared to wedge resection (HR:0.52, 95 %CI: 0.41–0.67, p &lt; 0.001). DFS outcomes were similar between lobectomy and sublobar resection (HR:0.98, 95 %CI: 0.84–1.14, p = 0.778).</p></div><div><h3>Conclusion</h3><p>Lobectomy is associated with better overall survival compared to sublobar resection in NSCLC patients. However, when sublobar resection is subdivided, segmentectomy shows comparable outcomes to lobectomy, while wedge resection is inferior. These findings support the consideration of segmentectomy as the surgical option of choice for Stage IA NSCLC patients.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107929"},"PeriodicalIF":4.5,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142020796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized trial of anetumab ravtansine and pembrolizumab compared to pembrolizumab for mesothelioma","authors":"Aaron S. Mansfield ,&nbsp;Jun Vivien Yin ,&nbsp;Penelope Bradbury ,&nbsp;David J. Kwiatkowski ,&nbsp;Shiven Patel ,&nbsp;Lyudmila A. Bazhenova ,&nbsp;Patrick Forde ,&nbsp;Yanyan Lou ,&nbsp;Paul Dizona ,&nbsp;Liza C. Villaruz ,&nbsp;Susanne M. Arnold ,&nbsp;Maya Khalil ,&nbsp;Hedy L. Kindler ,&nbsp;Marianna Koczywas ,&nbsp;Jose Pacheco ,&nbsp;Christian Rolfo ,&nbsp;Bing Xia ,&nbsp;Elizabeth Mikula ,&nbsp;Li Chen ,&nbsp;Kashish Patel ,&nbsp;Raffit Hassan","doi":"10.1016/j.lungcan.2024.107928","DOIUrl":"10.1016/j.lungcan.2024.107928","url":null,"abstract":"<div><h3>Purpose</h3><p>The mesothelin-targeting antibody-drug conjugate anetumab ravtansine was evaluated in combination with the programmed cell death-1 (PD-1) inhibitor pembrolizumab based on the common expression of mesothelin and reports of activity in mesothelioma.</p></div><div><h3>Patients and methods</h3><p>A phase 1 safety run-in of the combination of anetumab ravtansine (6.5 mg/kg iv q3weeks) and pembrolizumab (200 mg, IV q3weeks) was conducted, followed by a phase 2 randomization to the combination or pembrolizumab alone at medical centers across the United States and Canada in the National Cancer Institute’s Experimental Therapeutics Clinical Trials Network. Patients with pleural mesothelioma that expressed mesothelin and had previously received platinum-based therapy were eligible.</p></div><div><h3>Results</h3><p>In phase 1 (n = 12) only one dose limiting toxicity was observed and the rules for dose reduction were not met. In phase 2, there was no difference in the confirmed response rates between the combination group (n = 18, 2 partial responses [PR], 11 %) and the pembrolizumab group (n = 17, 1 PR, 6 %; z = -0.5523, p = 0.29116). The median PFS was 12.2 months (95 % CI 5.1–not evaluable [NE]) for the combination, and 3.9 months for pembrolizumab (95 % CI 2.1-NE)(HR=0.55, p = 0.20). Patients with high baseline levels of soluble mesothelin who received anetumab ravtansine had a median PFS of 5 months.</p></div><div><h3>Conclusions</h3><p>The numeric difference in PFS between treatment groups was not statistically significant, likely related to a smaller than planned sample size. High levels of soluble mesothelin should potentially be considered to select against the use of mesothelin-targeting therapies in development that are neutralized by soluble mesothelin.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107928"},"PeriodicalIF":4.5,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142083471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-invasive diagnosis of pulmonary nodules by circulating tumor DNA methylation: A prospective multicenter study","authors":"Ying Li ,&nbsp;Fangfang Xie ,&nbsp;Qiang Zheng ,&nbsp;Yujun Zhang ,&nbsp;Wei Li ,&nbsp;Minjie Xu ,&nbsp;Qiye He ,&nbsp;Yuan Li ,&nbsp;Jiayuan Sun","doi":"10.1016/j.lungcan.2024.107930","DOIUrl":"10.1016/j.lungcan.2024.107930","url":null,"abstract":"<div><h3>Background</h3><p>With the popularization of computed tomography, more and more pulmonary nodules (PNs) are being detected. Risk stratification of PNs is essential for detecting early-stage lung cancer while minimizing the overdiagnosis of benign nodules. This study aimed to develop a circulating tumor DNA (ctDNA) methylation-based, non-invasive model for the risk stratification of PNs.</p></div><div><h3>Methods</h3><p>A blood-based assay (“LUNG-TRAC”) was designed to include novel lung cancer ctDNA methylation markers identified from in-house reduced representative bisulfite sequencing data and known markers from the literature. A stratification model was trained based on 183 ctDNA samples derived from patients with benign or malignant PNs and validated in 62 patients. LUNG-TRAC was further single-blindly tested in a single- and multi-center cohort.</p></div><div><h3>Results</h3><p>The LUNG-TRAC model achieved an area under the curve (AUC) of 0.810 (sensitivity = 74.4 % and specificity = 73.7 %) in the validation set. Two test sets were used to evaluate the performance of LUNG-TRAC, with an AUC of 0.815 in the single-center test (N = 61; sensitivity = 67.5 % and specificity = 76.2 %) and 0.761 in the multi-center test (N = 95; sensitivity = 50.7 % and specificity = 80.8 %). The clinical utility of LUNG-TRAC was further assessed by comparing it to two established risk stratification models: the Mayo Clinic and Veteran Administration models. It outperformed both in the validation and the single-center test sets.</p></div><div><h3>Conclusion</h3><p>The LUNG-TRAC model demonstrated accuracy and consistency in stratifying PNs for the risk of malignancy, suggesting its utility as a non-invasive diagnostic aid for early-stage peripheral lung cancer.</p></div><div><h3>Clinical trial registration</h3><p><span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span> (NCT03989219).</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107930"},"PeriodicalIF":4.5,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169500224004641/pdfft?md5=b89dd581a2a735dceff419eabb3bd3f8&pid=1-s2.0-S0169500224004641-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world outcomes of atypical EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) treated with osimertinib (osi) vs. Afatinib or erlotinib","authors":"Adam Barsouk ,&nbsp;Omar Elghawy ,&nbsp;Alec Heidlauf ,&nbsp;Connie Yu ,&nbsp;Lucy Wang ,&nbsp;David Yang ,&nbsp;Martin Kurian ,&nbsp;Keshav Goel ,&nbsp;Lynn Rushkin ,&nbsp;Anna Anran Huang ,&nbsp;Lauren Reed-Guy ,&nbsp;Benjamin Bleiberg ,&nbsp;Lova Sun ,&nbsp;Aditi Singh ,&nbsp;Roger B. Cohen ,&nbsp;Charu Aggarwal ,&nbsp;Melina Marmarelis ,&nbsp;Corey Langer","doi":"10.1016/j.lungcan.2024.107926","DOIUrl":"10.1016/j.lungcan.2024.107926","url":null,"abstract":"<div><h3>Objectives</h3><p>Limited data are available comparing the efficacy of osi versus earlier generation TKIs for mNSCLC with atypical <em>EGFR</em> mutations (AMs) such as L861Q, G719X, S768I and exon20.</p></div><div><h3>Methods</h3><p>We performed a single-institution retrospective analysis of patients with <em>EGFR</em>-mutated mNSCLC treated from 2007 to 2023 with 1L TKIs, comparing outcomes for AM patients treated with osi, afatinib, and erlotinib. Baseline demographics, disease characteristics, treatment history, toxicity, and clinical outcomes were abstracted from the electronic medical record and compared between TKIs using independent sample t-tests and chi-square analyses. Median progression free survival (mPFS) and overall survival (mOS) were compared via Kaplan-Meier log-rank analysis and Cox multivariable regression.</p></div><div><h3>Results</h3><p>Among 355 patients with <em>EGFR</em>-mutated mNSCLC, 36 (10 %) harbored AMs in G719X (N=21; 6 %), Exon 20 (N=11; 3 %), L861Q (N=7; 2 %), S768I (N=4; 1 %), C797S (N=1; 0.3 %); 6 patients had compound mutations. Patients with classical mutations (CMs) vs AMs had similar baseline demographic and disease characteristics and usage of TKIs (p = 0.124). Among AM patients, osi yielded superior mPFS (22 m) vs afatinib (12 m; p = 0.005) or erlotinib (9 m; p = 0.001). mOS was likewise superior for osi (32 m) vs afatinib (21 m; p = 0.032) or erlotinib (17 m; p = 0.011). Dose-reduction rates due to AEs were lower for osi (19 %) vs afatinib (24 %; p = 0.003) or erlotinib (23 %; p = 0.002). Discontinuation rates due to AEs were lower for osi vs afatinib (1 % vs 2 %; p &lt; 0.001) or erlotinib (2 %; p = 0.004).</p></div><div><h3>Conclusions</h3><p>In a large real-world analysis, osi demonstrated superior progression-free and overall survival and improved tolerability compared to afatinib or erlotinib for atypical <em>EGFR</em>-mutated mNSCLC.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107926"},"PeriodicalIF":4.5,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141954230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Five-year survival in patients with extensive-stage small cell lung cancer treated with atezolizumab in the Phase III IMpower133 study and the Phase III IMbrella A extension study","authors":"Martin Reck ,&nbsp;Rafal Dziadziuszko ,&nbsp;Shunichi Sugawara ,&nbsp;Steven Kao ,&nbsp;Maximilian Hochmair ,&nbsp;Florian Huemer ,&nbsp;Gilberto de Castro Jr ,&nbsp;Libor Havel ,&nbsp;Reyes Bernabé Caro ,&nbsp;György Losonczy ,&nbsp;Jong-Seok Lee ,&nbsp;Dariusz M. Kowalski ,&nbsp;Zoran Andric ,&nbsp;Raffaele Califano ,&nbsp;Andrea Veatch ,&nbsp;Gregory Gerstner ,&nbsp;Marta Batus ,&nbsp;Stefanie Morris ,&nbsp;Monika Kaul ,&nbsp;Vaikunth Cuchelkar ,&nbsp;Stephen V. Liu","doi":"10.1016/j.lungcan.2024.107924","DOIUrl":"10.1016/j.lungcan.2024.107924","url":null,"abstract":"<div><h3>Objectives</h3><p>IMbrella A is a Phase III extension study that allowed rollover from Roche/Genentech–sponsored atezolizumab trials, including IMpower133, a Phase I/III trial of first-line atezolizumab or placebo plus carboplatin/etoposide in extensive-stage small cell lung cancer. We report outcomes from an exploratory analysis of IMpower133 with extended time-to-event data for patients who rolled over to IMbrella A.</p></div><div><h3>Materials and Methods</h3><p>IMpower133 patients could roll over to IMbrella A to receive atezolizumab 1200 mg intravenously every three weeks if they continued to receive atezolizumab at IMpower133 closure or were in survival follow-up after atezolizumab discontinuation. Overall survival and safety were assessed; only serious adverse events and AEs of special interest were collected in IMbrella A.</p></div><div><h3>Results</h3><p>Eighteen of 26 eligible patients rolled over to IMbrella A. At clinical cutoff (March 16, 2023), median follow-up in the atezolizumab plus carboplatin/etoposide arm (IMpower133 and IMbrella A) was 59.4 months. The three-, four-, and five-year overall survival (95 % CI) estimates were 16 % (11 %–21 %), 13 % (8 %–18 %), and 12 % (7 %–17 %), respectively. In IMbrella A, serious adverse events occurred in three patients (16.7 %), and one adverse event of special interest was reported (grade two hypothyroidism).</p></div><div><h3>Conclusion</h3><p>This long-term analysis of patients from IMbrella A previously enrolled in IMpower133 provides the first report of five-year overall survival outcomes in patients with extensive-stage small cell lung cancer treated with first-line cancer immunotherapy and chemotherapy. While limited by small patient numbers and lack of long-term data for the IMpower133 control arm, exploratory overall survival analyses in patients treated with atezolizumab plus carboplatin/etoposide compared favorably with historical data with chemotherapy alone.</p><p>NCT03148418.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107924"},"PeriodicalIF":4.5,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive value and molecular correlates of MYC immunohistochemistry and copy number gain in non-small cell lung carcinomas treated with immunotherapy","authors":"Julia Naso ,&nbsp;Aakash Desai ,&nbsp;Caleb J. Smith ,&nbsp;Yash P. Ashara ,&nbsp;Stephen Yip ,&nbsp;Ying-Chun Lo","doi":"10.1016/j.lungcan.2024.107927","DOIUrl":"10.1016/j.lungcan.2024.107927","url":null,"abstract":"<div><h3>Objectives</h3><p>Accurately predicting which patients diagnosed with non-small cell lung cancer (NSCLC) will respond to immunotherapy remains a clinical challenge. This study aims to determine the associations between MYC immunoreactivity, <em>MYC</em> copy number gain (CNG), driver mutations and survival following immunotherapy treatment, to provide insight into whether clinical MYC assessment may have predictive value.</p></div><div><h3>Materials and Methods</h3><p>MYC copy number status was determined in 82 patients with NSCLC treated with immunotherapy, and MYC immunohistochemistry (IHC) was performed on 80 of these cases. MYC staining in ≥ 40 % of tumor cells was considered positive. Driver gene alterations, PD-L1 status and survival outcomes were assessed through retrospective chart review. Overall survival (OS) and progression free survival (PFS) were calculated from the date of immunotherapy initiation.</p></div><div><h3>Results</h3><p>Nine (11 %) of 82 cases had <em>MYC</em> CNG and 56 (70 %) of the 80 immunostained cases were positive for MYC. <em>MYC</em> CNG was significantly associated with <em>STK11</em> mutation (P=0.023), whereas positive MYC IHC was significantly associated with <em>KRAS</em> mutation (P=0.0076) and current/former smoking (P=0.0007). <em>MYC</em> CNG and positive MYC IHC were not significantly associated with each other (P=0.42), or with PD-L1 ≥ 1 % (MYC CNG: P=0.10; MYC IHC: P=0.09). Positive MYC IHC and PD-L1 ≥ 1 % were both significant predictors of OS (MYC: HR 2.7, 95 % CI 1.1–6.4, P=0.026; PD-L1: HR 0.33, 95 % CI 0.15–0.72, P=0.0055). MYC IHC positive/PD-L1 &lt; 1 % cases had the shortest OS (median 230 versus 918 days, P=0.00069) and PFS (median 84 versus 254 days, P=0.0087). <em>MYC</em> CNG was not associated with OS or PFS.</p></div><div><h3>Conclusion</h3><p>We find that positive MYC IHC is an independent predictor of shorter OS after immunotherapy treatment, with MYC positive/PD-L1 &lt; 1 % status predictive of particularly poor immunotherapy response. We identify positive MYC IHC as a feature of possible relevance to NSCLC treatment selection and of interest for future therapy development.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107927"},"PeriodicalIF":4.5,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142011518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}