JTO Clinical and Research Reports最新文献

{"title":"Temporal Trends in the Utilization and Survival Outcomes of Lobar, Segmental, and Wedge Resection for Early-Stage NSCLC, 2004 to 2020","authors":"Eden Z. Deng BS ,&nbsp;Xiaofei Wang PhD ,&nbsp;Jianrong Zhang MD, MPH ,&nbsp;Thomas E. Stinchcombe MD ,&nbsp;Chi-Fu (Jeffrey) Yang MD ,&nbsp;Nasser Altorki MD","doi":"10.1016/j.jtocrr.2025.100794","DOIUrl":"10.1016/j.jtocrr.2025.100794","url":null,"abstract":"<div><h3>Introduction</h3><div>Although lobectomy has long been the standard of surgical treatment for early-stage NSCLC, segmental and wedge resections have become another option often used over the past two decades.</div></div><div><h3>Methods</h3><div>To examine the trends over time in the utilization, quality, and overall survival (OS) differences of lobectomy, segmentectomy, and wedge resection, we performed an observational, population-level study of 76,466 patients with T1 or T2 N0M0 NSCLC tumors 2 cm or less in size in the National Cancer Database, from 2004 to 2020. To compare the OS of the three treatments, we used inverse probability of treatment weighting to analyze a subgroup of cases with nodal examination and minimal comorbidity burden.</div></div><div><h3>Results</h3><div>From 2004 to 2020, the use of lobectomy decreased from 75.2% to 67.6% of resections, wedge remained relatively stable (20.5%–22.8%), and segmentectomy increased from 4.3% to 9.7%. The likelihood of nodal assessments and negative margins has increased for all treatments. Younger patients, patients with low comorbidity burden, and patients with smaller tumors have become increasingly likely to receive segmental and wedge resections. Five-year OS of segmentectomy (80.6%, 95% confidence interval [CI]: 78.1%–83.2%) remained noninferior to lobectomy (83.6%, 95% CI: 83.1%–84.1%]), whereas wedge resection was inferior until 2016 to 2019 (five-y OS = 79.9%, 95% CI: 75.9%–83.8%).</div></div><div><h3>Conclusions</h3><div>Sublobar resections, particularly segmentectomies, have increased in frequency and quality. The growing use of sublobar resections for younger and healthier patients highlights the need for additional clinical evidence demonstrating whether these trends do indeed lead to better outcomes.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100794"},"PeriodicalIF":3.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Immune Checkpoint Inhibitors and Local Radical Treatment on Survival Outcomes in Synchronous Oligometastatic NSCLC","authors":"Mandy Jongbloed MD ,&nbsp;Valentina Bartolomeo MD ,&nbsp;Martina Bortolot MD ,&nbsp;Shahan Darwesh MD ,&nbsp;Jarno W.J. Huijs MD ,&nbsp;Safiye Dursun MD ,&nbsp;Juliette Degens MD, PhD ,&nbsp;Ben E.E.M. van den Borne MD, PhD ,&nbsp;Maggy Youssef-El Soud MD, PhD ,&nbsp;Marcel Westenend MD, PhD ,&nbsp;Cordula Pitz MD, PhD ,&nbsp;Dirk K.M. De Ruysscher MD, PhD ,&nbsp;Lizza E.L. Hendriks MD, PhD","doi":"10.1016/j.jtocrr.2025.100790","DOIUrl":"10.1016/j.jtocrr.2025.100790","url":null,"abstract":"<div><h3>Introduction</h3><div>The impact of an immune checkpoint inhibitor (ICI)–based systemic treatment strategy with or without local radical treatment (LRT) on outcomes for patients with NSCLC and synchronous oligometastatic disease (sOMD) is unknown.</div></div><div><h3>Methods</h3><div>Multicenter retrospective study including adequately staged patients, with sOMD NSCLC (maximum five metastases in three organs [European Organization for Research and Treatment of Cancer definition]) between January 1, 2015 and December 31, 2022, treated with a first-line ICI-based versus chemotherapy-only regimen. Primary end points were progression-free survival and overall survival (OS) for an ICI-based versus chemotherapy-only strategy. Subgroup analyses were performed for patients who were deemed candidates for LRT in the multidisciplinary meeting and those proceeding to LRT.</div></div><div><h3>Results</h3><div>A total of 416 patients were included, treated with chemotherapy-ICI (n = 138) or chemotherapy-only (n = 278), 319 out of 416 were deemed candidates by multidisciplinary meetings for LRT, whereas 192 (60%) proceeded to LRT. The median OS was significantly longer in the chemotherapy-ICI compared with the chemotherapy-only group (33.6 versus 15.9 mo, hazard ratio [HR] = 0.5, 95% confidence interval [CI]: 0.4–0.7, <em>p</em> &lt; 0.001), in the subgroups who were candidate for LRT (36.1 versus 17.2 mo, HR = 0.5, 95% CI: 0.4–0.7, <em>p</em> &lt; 0.001) and those proceeding to LRT (not reached versus 23.1 mo, HR = 0.4, 95% CI: 0.2–0.7, <em>p</em> &lt; 0.001). In multivariate analysis, an ICI-based strategy was associated with improved survival in the total group (HR = 0.6, 95% CI: 0.4–0.9, <em>p</em> &lt; 0.001), in those with intention of LRT (HR = 0.6, 95% CI: 0.4–0.9, <em>p</em> = 0.02) and those who proceeded to LRT (HR = 0.3, 95% CI: 0.1–0.6, <em>p</em> = 0.002).</div></div><div><h3>Conclusions</h3><div>An ICI-based systemic treatment strategy (±LRT) is associated with improved survival compared with chemotherapy-only (±LRT) for patients with sOMD NSCLC. Prospective randomized trial data are necessary to identify patients most likely to benefit from adding LRT.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100790"},"PeriodicalIF":3.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143173716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol Vaping–Associated Multifocal NSCLC in a 24-Year-Old Female: A Case Report","authors":"Mansi Barthwal MD ,&nbsp;Nataliya Moldovan MD ,&nbsp;Shantanu Banerji MD ,&nbsp;Julian O. Kim MD","doi":"10.1016/j.jtocrr.2025.100789","DOIUrl":"10.1016/j.jtocrr.2025.100789","url":null,"abstract":"<div><div>Vaping use among Canadian youth is rising but the long-term sequelae of cannabidiol (CBD) vaping are not yet elucidated. Vaping aerosols contain carcinogens; however, owing to the latency period between carcinogen exposure and clinical presentation of malignancies, at present, there is a paucity of reported CBD vaping–associated lung cancers. We present the case of a 24-year-old female with nonspecific respiratory symptoms who developed multifocal NSCLC attributable to extensive CBD vaping.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100789"},"PeriodicalIF":3.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel PLEC-EML4-ALK Double Fusion Underlying Crizotinib Resistance in a Metastatic Inflammatory Myofibroblastic Tumor: A Case Report","authors":"Alessandra Maleddu MD ,&nbsp;Trista K. Hinz MS ,&nbsp;Margaret A. Black MD ,&nbsp;Dara L. Aisner MD, PhD ,&nbsp;Carrie B. Marshall MD ,&nbsp;Anthony D. Elias MD ,&nbsp;Breelyn A. Wilky MD ,&nbsp;Lynn E. Heasley PhD ,&nbsp;Kurtis D. Davies PhD","doi":"10.1016/j.jtocrr.2025.100791","DOIUrl":"10.1016/j.jtocrr.2025.100791","url":null,"abstract":"<div><div><em>ALK</em> fusions are frequent oncogenic drivers in inflammatory myofibroblastic tumors. Treatment with crizotinib is effective in fusion-positive patients; however, acquired resistance remains a challenge. Here, we present a case of <em>EML4-ALK</em>-positive metastatic inflammatory myofibroblastic tumor that initially responded to crizotinib but developed resistance. The progressing lesion revealed the acquisition of a “double fusion” event in which <em>EML4-ALK</em> was additionally fused to <em>PLEC</em> to create a <em>PLEC-EML4-ALK</em> transcript. The double fusion was associated with an increase in <em>ALK</em> expression, mimicking the <em>ALK</em> fusion amplification that is a known mechanism of resistance to crizotinib in lung cancer. On transition to the more potent ALK inhibitor alectinib, the patient exhibited a dramatic response. Thus, the formation of a double fusion represents a novel and targetable mechanism of resistance to crizotinib.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 5","pages":"Article 100791"},"PeriodicalIF":3.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucocutaneous Adverse Events in Patients With Cancer Treated with the Highly Selective RET Kinase Inhibitor Selpercatinib (LOXO-292)","authors":"Rachel E. Reingold MD ,&nbsp;Rose Parisi MD, MBA ,&nbsp;Guilherme Harada MD ,&nbsp;Andrea P. Moy MD ,&nbsp;George Dranitsaris PhD ,&nbsp;Jasmine H. Francis MD ,&nbsp;Julia Canestraro OD, FAAO ,&nbsp;Julia A. Lester MPH ,&nbsp;Lauren A. Kaplanis RN ,&nbsp;Dazhi Liu PharmD, BCOP ,&nbsp;Mario E. Lacouture MD ,&nbsp;Alexander Drilon MD","doi":"10.1016/j.jtocrr.2025.100792","DOIUrl":"10.1016/j.jtocrr.2025.100792","url":null,"abstract":"<div><h3>Introduction</h3><div>Selective RET inhibitors are approved for the treatment of RET-dependent cancers. A comprehensive characterization of mucocutaneous adverse events (MAEs) has not been performed; therefore, we characterized MAEs associated with the selective RET inhibitor, selpercatinib.</div></div><div><h3>Methods</h3><div>We assessed 133 patients with <em>RET-</em>altered cancers treated with selpercatinib. The type, grade, cumulative incidence, and time to onset of MAEs were determined. Therapy interruptions, clinicopathologic findings, and management were described. Laboratory values were compared between patients with and without MAEs.</div></div><div><h3>Results</h3><div>A total of 73 patients with mostly NSCLC (n = 46, 63%), medullary thyroid (n = 19, 26%), and papillary thyroid (n = 6, 8%) cancers had 126 predominantly grade 1/2 (n = 124, 98%) MAEs, with 48% reporting greater than one MAE. Xerostomia (n = 49, 37%), rash (n = 24, 18%), periorbital edema (n = 16, 12%), and xerosis (n = 12, 9%) were the most common MAEs. The yearly cumulative incidence of all-grade MAEs was 55%, with a median time to onset of 57 (interquartile range: 15–166) days after initiation. Those with MAEs had a significantly higher percentage of lymphocytes (mean = 21.8, SD = 11.3, <em>p</em> = 0.005) compared with those without MAEs (16.9, SD = 10.0) and elevated immunoglobulin E (mean = 275, SD = 294.5 IU/mL). There were 18 (14%) MAE-related therapy interruptions, including the following: three (2%) rechallenged with dose maintained, 10 (7%) with a 50% dose reduction, 5 (4%) with a 25% dose reduction, and no drug discontinuations. A treatment algorithm was created for the most common MAEs: xerostomia managed with saliva and lubricants; mucositis with steroid rinses; rashes with topical steroids with or without topical ammonium lactate; periorbital edema with cold or caffeine compresses; and xerosis and pruritus with emollients.</div></div><div><h3>Conclusions</h3><div>Selective RET inhibition is associated with a unique MAE profile. Early recognition and management of MAEs may improve quality of life, minimize interruptions, and maximize therapeutic benefit.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100792"},"PeriodicalIF":3.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143173715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fam-Trastuzumab-Deruxtecan and Osimertinib Combination to Target HER2 Driven Resistance in a Patient With NSCLC After Osimertinib Progression: Case Report","authors":"Hailey M. Hirata PharmD ,&nbsp;Carrie B. Lee MD, MPH ,&nbsp;Kevin Y. Chen PharmD, MS","doi":"10.1016/j.jtocrr.2025.100787","DOIUrl":"10.1016/j.jtocrr.2025.100787","url":null,"abstract":"<div><div>HER2 mutations have been identified as potential mechanisms of resistance to EGFR-directed therapies in patients with advanced or metastatic NSCLC. Here, we report the case of a 65-year-old female with metastatic, EGFR exon 19–mutant NSCLC initially treated with first-line osimertinib. After several subsequent lines of treatment including erlotinib and carboplatin+pemetrexed+osimertinib, repeat genetic sequencing identified a HER2 exon 20 insertion (A775_G776insYVMA) in both blood and tissue. She was treated using fam-trastuzumab-deruxtecan, which resulted in a disease response lasting for 8 months. This report represents the first published case detailing the safety and efficacy of a combination fam-trastuzumab-deruxtecan and osimertinib in a patient with NSCLC and HER2-mutated resistance after EGFR-targeted therapy. The findings from this report suggest that fam-trastuzumab-deruxtecan can be safely given in combination with osimertinib and should be considered as subsequent-line therapy for patients who progress on osimertinib and develop a HER2 resistance mutation.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 4","pages":"Article 100787"},"PeriodicalIF":3.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Tracking of ALK-Rearranged NSCLC From Plasma Using Circulating Tumor RNA and Circulating Tumor DNA","authors":"Simon Heeke PhD ,&nbsp;Saumil Gandhi MD, PhD ,&nbsp;Hai T. Tran PharmD ,&nbsp;Vincent K. Lam MD ,&nbsp;Lauren A. Byers MD ,&nbsp;Don L. Gibbons MD, PhD ,&nbsp;Carl M. Gay MD, PhD ,&nbsp;Mehmet Altan MD ,&nbsp;Mara B. Antonoff MD, FACS ,&nbsp;Xiuning Le MD, PhD ,&nbsp;Janet Tu MD ,&nbsp;Maliazurina B. Saad PhD ,&nbsp;Michelle Pek PhD ,&nbsp;Jonathan Poh PhD ,&nbsp;Kao Chin Ngeow DPhil ,&nbsp;Anne Tsao MD, MBA, FACHE ,&nbsp;Tina Cascone MD, PhD ,&nbsp;Marcelo V. Negrao MD ,&nbsp;Jia Wu PhD ,&nbsp;George R. Blumenschein Jr. MD ,&nbsp;Yasir Y. Elamin MD","doi":"10.1016/j.jtocrr.2025.100795","DOIUrl":"10.1016/j.jtocrr.2025.100795","url":null,"abstract":"<div><h3>Background</h3><div>Although the administration of tyrosine-kinase inhibitors in <em>ALK</em>-rearranged NSCLC has revolutionized precision medicine, the detection of gene rearrangements from liquid biopsies remains challenging. RNA-based detection has revealed promising sensitivity for rearrangement detection and thus we hypothesize that a liquid biopsy assay analyzing circulating tumor RNA (ctRNA) in addition to circulating tumor DNA (ctDNA) will improve detection. Furthermore, we hypothesize that the detection of gene fusions at baseline will correlate with clinical outcomes.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 86 plasma samples from 33 patients enrolled in the BRIGHTSTAR clinical trial assessing local consolidative therapy (LCT) and brigatinib in patients with stage IV or recurrent NSCLC and confirmed <em>ALK</em> rearrangement (NCT03707938) using a targeted next-generation sequencing assay that analyzes ctDNA to detect gene rearrangements and mutations in 80 genes and ctRNA to detect gene arrangements in 36 genes.</div></div><div><h3>Results</h3><div><em>ALK</em> rearrangements were detected in 15 of 28 patients (54%) at baseline, of which eight were detected in both ctDNA and ctRNA. <em>ALK</em> rearrangements were detected in two patients pre-LCT, exclusively in ctRNA, but cleared completely post-LCT. The detection of <em>ALK</em> fusion at baseline was associated with significantly worse progression-free survival (<em>p</em> = 0.033). Plasma cell-free DNA concentrations for patients with detectable <em>ALK</em> rearrangements at baseline were significantly higher than for those without detectable gene fusions (12.3 ng/mL versus 20.2 ng/mL, <em>p</em> = 0.0046).</div></div><div><h3>Conclusions</h3><div>The inclusion of ctRNA in liquid biopsies increased detection of <em>ALK</em> rearrangements and detection at baseline was associated with significantly worse progression-free survival highlighting the added benefit of ctRNA.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 4","pages":"Article 100795"},"PeriodicalIF":3.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring of Circulating Tumor DNA and Indication of De-Escalation Adjuvant Targeted Therapy for EGFR-Mutated NSCLC After Complete Resection","authors":"Song Dong PhD ,&nbsp;Bingfa Yan PhD ,&nbsp;Si-Yang Liu PhD ,&nbsp;Xuan Gao PhD ,&nbsp;Hui-Zhao Hong MD ,&nbsp;Hong-Ji Li MD ,&nbsp;Wei Gao PhD ,&nbsp;Hong-Hong Yan PhD ,&nbsp;Si-Yang Maggie Liu PhD ,&nbsp;Hai-Yan Tu PhD ,&nbsp;Yi Pan PhD ,&nbsp;Qing Zhou PhD ,&nbsp;Xue-Ning Yang PhD ,&nbsp;Xue-Feng Xia PhD ,&nbsp;Xin Yi PhD ,&nbsp;Wen-Zhao Zhong PhD ,&nbsp;Yi-Long Wu MD ,&nbsp;Jia-Tao Zhang PhD","doi":"10.1016/j.jtocrr.2024.100758","DOIUrl":"10.1016/j.jtocrr.2024.100758","url":null,"abstract":"<div><h3>Introduction</h3><div>EGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA <em>EGFR</em>-mutated NSCLC. Nevertheless, adapting this approach to include a molecular residual disease (MRD)-guided de-escalation strategy warrants further investigation.</div></div><div><h3>Methods</h3><div>From January 2019 to December 2022, 71 patients with stages I to III NSCLC and <em>EGFR</em> (exon 19 deletion or L858R) mutations were enrolled in this observational study. A total of 375 blood samples were analyzed using the MRD_Navigator assay. Among them, 27 patients suspended EGFR TKI treatment based on undetectable MRD and were thus included in the adaptive, de-escalation group.</div></div><div><h3>Results</h3><div>Overall, the sensitivity of longitudinal MRD was 86.2%. Only four patients (11.8%) recurred with longitudinal undetectable MRD, indicating a negative predictive value of 88.2%. Of the patients who had detectable MRD after surgery, nine subsequently received EGFR TKI treatment, with only one (11.1%) achieving persistent circulating tumor DNA clearance post–EGFR TKI. Furthermore, 22 patients with stages IB to III disease who had previously suspended their TKI treatment based on undetectable MRD were included in the adaptive group, with an average duration of TKI 3.9 (range: 0–35.0) months. The 2-year disease-free survival rate of these 22 patients was 80.2%, and the median was not reached. Five patients (n = 5 of 22, 22.7%) had disease recurrence during the period of drug cessation but were stable under EGFR TKI treatment until the latest follow-up. Two patients remained in complete remission.</div></div><div><h3>Conclusions</h3><div>Our initial findings underscore the potential of an adaptive, de-escalation approach to adjuvant EGFR TKIs based on circulating tumor DNA-MRD monitoring.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 1","pages":"Article 100758"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief Report: Not Created Equal: Survival Differences by KRAS Mutation Subtype in NSCLC Treated With Immunotherapy","authors":"Lova Sun MD, MSCE ,&nbsp;Yunyun Zhou PhD ,&nbsp;Elizabeth A. Handorf PhD ,&nbsp;Hossein Borghaei DO ,&nbsp;Jessica Bauman MD ,&nbsp;Charu Aggarwal MD","doi":"10.1016/j.jtocrr.2024.100755","DOIUrl":"10.1016/j.jtocrr.2024.100755","url":null,"abstract":"<div><h3>Introduction</h3><div>The predictive and prognostic implications of different <em>KRAS</em> mutation (<em>KRAS</em>m) subtypes in metastatic NSCLC have not been clearly defined. We used a nationwide observational database to investigate whether <em>KRAS</em>m subtypes differ in their association with survival in metastatic NSCLC treated with immune checkpoint inhibitor (ICI)-based therapy, across programmed death-ligand 1 (PD-L1) levels.</div></div><div><h3>Methods</h3><div>Patients with advanced nonsquamous NSCLC who initiated first-line ICI-based therapy from 2016 to 2021 and had known PD-L1 expression and comprehensive genomic profiling including <em>KRAS</em>, <em>STK11</em>, <em>KEAP1</em>, and <em>TP53</em> were included. Within PD-L1 expression subgroups (&lt;1%, 1%–49%, ≥50%), Cox multivariable regression was used to evaluate the association between <em>KRAS</em>m subtypes (G12C, G12V, G12D, other <em>KRAS</em>m) and overall survival, estimated using Kaplan-Meier methodology.</div></div><div><h3>Results</h3><div>Among the 1539 patients, 819 patients were <em>KRAS</em> wild type (<em>KRAS</em>wt) and 720 were <em>KRAS</em>m (296 <em>KRAS</em> G12C, 143 <em>KRAS</em> G12V, 97 <em>KRAS</em> G12D, 184 other <em>KRAS</em>m). In the 50% or higher PD-L1 subgroup, patients with <em>KRAS</em> G12V had worse survival (median overall survival [mOS] = 8.2 mo) compared with <em>KRAS</em>wt (mOS = 13.3 mo) and other <em>KRAS</em> subgroups (mOS ranging from 13.4 to 19.9 mo). On adjusted Cox multivariable regression in the 50% or higher PD-L1 subgroup, the hazard ratio for death for <em>KRAS</em> G12V ranged from 1.53 to 1.78 compared with <em>KRAS</em>wt and other <em>KRAS</em>m subtypes (all <em>p</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>Although patients with 50% or higher PD-L1 with <em>KRAS</em> G12C, G12D, and other subtypes exhibited similar survival to <em>KRAS</em>wt, <em>KRAS</em> G12V was associated with significantly worse survival than <em>KRAS</em>wt and other <em>KRAS</em>m subtypes. All <em>KRAS</em>m should not be regarded as uniform predictors of ICI responsiveness, even with high PD-L1 expression; <em>KRAS</em> G12V tumors may have worse outcomes with ICI-based therapy and benefit from treatment intensification.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 1","pages":"Article 100755"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to ‘Brief Report: Clinical Outcomes by Infusion Timing of Immune Checkpoint Inhibitors in Patients With Locally Advanced NSCLC’ [JTO Clinical and Research Reports, Volume 5 Issue 4 (2024) 100659]","authors":"Tsuyoshi Hirata MD ,&nbsp;Yuji Uehara MD ,&nbsp;Taiki Hakozaki MD ,&nbsp;Takayuki Kobayashi MD ,&nbsp;Yuto Terashima MD ,&nbsp;Kageaki Watanabe MD ,&nbsp;Makiko Yomota MD, PhD ,&nbsp;Yukio Hosomi MD, PhD","doi":"10.1016/j.jtocrr.2024.100761","DOIUrl":"10.1016/j.jtocrr.2024.100761","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 1","pages":"Article 100761"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}