JTO Clinical and Research Reports最新文献

{"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":"Racial Disparities in Cancer Guideline-Concordant Treatment Using Surveillance, Epidemiology, and End Results Data for Patients With NSCLC","authors":"Eric Ababio Anyimadu MS ,&nbsp;Jacklyn M. Engelbart MD ,&nbsp;Jason Semprini PhD ,&nbsp;Amanda Kahl MPH ,&nbsp;Cameron Trentz MS ,&nbsp;John M. Buatti MD ,&nbsp;Thomas L. Casavant PhD ,&nbsp;Mary E. Charlton PhD ,&nbsp;Guadalupe Canahuate PhD","doi":"10.1016/j.jtocrr.2024.100747","DOIUrl":"10.1016/j.jtocrr.2024.100747","url":null,"abstract":"<div><h3>Introduction</h3><div>Despite efforts to achieve health care equality, racial/ethnic disparities persist in lung cancer survival in the United States, with non-Hispanic Black patients experiencing higher mortality compared with non-Hispanic Whites. Previous research often focused on single treatments, overlooking the broad range of options available. We aimed to highlight disparities in survival and receipt of comprehensive lung cancer treatment by developing a guideline-concordant initial treatment (GCIT) indicator based on disease stage and recommended treatment.</div></div><div><h3>Methods</h3><div>Using data of the Surveillance, Epidemiology, and End Results on 377,370 patients with NSCLC, we derived a GCIT indicator based on National Comprehensive Cancer Network guidelines. Observed probabilities and logistic regression models adjusted for age, disease stage, and race were used to assess racial disparities in treatment and survival, with the Kaplan-Meier method evaluating survival rates. Racial/ethnic groups analyzed included non-Hispanic White, non-Hispanic Black, Asian/Pacific Islander, Hispanic, and American Indian/Alaska Native.</div></div><div><h3>Results</h3><div>Non-Hispanic Black patients had lower odds of receiving GCIT (OR = 0.80; 95% confidence interval [CI]: 0.78–0.82) and surviving 2 years after diagnosis (OR = 0.80; 95% CI: 0.78–0.82). Non-Hispanic Asians had the highest odds of receiving GCIT (OR = 1.02; 95% CI: 0.99–1.05). Patients receiving GCIT had improved survival, with early stage patients experiencing median survival of 67 to 102 months, compared with 11 to 17 months for those without GCIT.</div></div><div><h3>Conclusion</h3><div>Receiving GCIT considerably improves survival across all races, though disparities in receipt are observed. Interventions are needed to ensure equitable access to guideline-concordant care and reduce survival disparities for patients.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 1","pages":"Article 100747"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932221","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}

{"title":"First-Line Chemo-Immunotherapy in SCLC: Outcomes of a Binational Real-World Study","authors":"Laura Moliner MD ,&nbsp;Núria Zellweger MSc ,&nbsp;Sabine Schmid MD ,&nbsp;Martina Bertschinger MD ,&nbsp;Christine Waibel MD ,&nbsp;Ferdinando Cerciello MD, PhD ,&nbsp;Patrizia Froesch MD ,&nbsp;Michael Mark MD ,&nbsp;Adrienne Bettini MD ,&nbsp;Pirmin Häuptle MD ,&nbsp;Veronika Blum MD ,&nbsp;Lisa Holer MSc ,&nbsp;Stefanie Hayoz PhD ,&nbsp;Martin Früh MD ,&nbsp;Samreen Ahmed FRCP, MD, MBBS, MSc ,&nbsp;Shradha Bhagani MD ,&nbsp;Nicola Steele MD ,&nbsp;Hannah-Leigh Gray BSc ,&nbsp;Stephen D. Robinson MD ,&nbsp;Michael Davidson MD (Res) ,&nbsp;Sacha I. Rothschild MD, PhD","doi":"10.1016/j.jtocrr.2024.100744","DOIUrl":"10.1016/j.jtocrr.2024.100744","url":null,"abstract":"<div><h3>Introduction</h3><div>SCLC is characterized by aggressiveness and limited treatment options, especially in extensive-stage SCLC (ES-SCLC). Immunotherapy added to the platinum-etoposide combination has recently become standard in this setting. This retrospective study aims to evaluate the real-world effectiveness of chemo-immunotherapy in patients with ES-SCLC, focusing on subpopulations excluded from clinical trials.</div></div><div><h3>Methods</h3><div>A retrospective binational multicenter study was conducted, involving consecutive patients with ES-SCLC from 10 British and 10 Swiss institutions. Patients received platinum-etoposide chemotherapy in combination with immunotherapy (atezolizumab or durvalumab). Patient, tumor, and treatment details were collected. Overall survival (OS), progression-free survival, objective response rate, and safety outcomes were analyzed.</div></div><div><h3>Results</h3><div>A total of 436 patients were included. One hundred forty-two patients (32.6%) in our cohort would not have been eligible for the pivotal registrational trials owing to an Eastern Cooperative Oncology Group performance status of 2 or higher, autoimmune disease, active brain metastases, or steroid use. Most patients received carboplatin (96.8%) and atezolizumab (97.9%). The median progression-free survival was 5.5 months and the median OS was 9.3 months. The two-year OS was 14%. Patients with liver or bone metastases or an Eastern Cooperative Oncology Group performance status of 2 or higher had worse survival outcomes. Treatment-related adverse events were reported in 222 patients (51%) whereas immune-related adverse events occurred in 95 patients (22%). Three out of five grade 5 immune-related adverse events were caused by pneumonitis.</div></div><div><h3>Conclusions</h3><div>To our knowledge, this is the largest real-world cohort of patients treated with chemo-immunotherapy for ES-SCLC. Although one-third of patients would not have been eligible for pivotal trials, the survival outcomes in our cohort are similar to those in registrational trials. In particular, the number of long-term survivors and the safety data are comparable, supporting the use of chemo-immunotherapy as first-line treatment for ES-SCLC in daily clinical practice.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 1","pages":"Article 100744"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971459","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":"Associations Between Patient-Reported Nutritional Status, Toxicity, and Survival in Limited-Stage SCLC","authors":"Evgenia Taranova ,&nbsp;Marianne Aanerud MD, PhD ,&nbsp;Tarje O. Halvorsen MD, PhD ,&nbsp;Kristin T. Killingberg MD, PhD ,&nbsp;Marit Slaaen MD, PhD ,&nbsp;Bjørn H. Grønberg MD, PhD","doi":"10.1016/j.jtocrr.2024.100764","DOIUrl":"10.1016/j.jtocrr.2024.100764","url":null,"abstract":"<div><h3>Introduction</h3><div>In general, malnutrition is associated with more treatment toxicity and shorter survival in patients with cancer, but little is known about its impact on limited-stage (LS) SCLC. We investigated whether nutritional status and weight loss were associated with treatment outcomes in a randomized trial of thoracic radiotherapy (TRT) in LS SCLC (NCT02041845, N = 170).</div></div><div><h3>Methods</h3><div>Patients received platinum-etoposide-chemotherapy and were randomized to receive TRT of 60 Gy in 40 fractions or 45 Gy in 30 fractions. They reported nutritional status on the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) and were categorized as having low (PG-SGA SF score 0–3), intermediate (score 4–8), or high (score ≥ 9) malnutrition risk.</div></div><div><h3>Results</h3><div>In total, 113 patients who completed the PG-SGA SF at baseline and received one or more fractions of TRT were analyzed. Median PG-SGA SF score was 3.0; 52.2% had low, 29.2% intermediate, and 18.6% had high malnutrition risk; and 22.1% had 5% or more weight loss three months before enrolment. There were no significant differences in grade 3 to 4 toxicity (low: 88.1%, intermediate: 90.9%, high: 85.7%; <em>p</em> = 0.86), median progression-free survival (low: 15.8 months, intermediate: 11.8 months, high: 47.0 months; <em>p</em> = 0.25) or median OS (low: 35.5 months, intermediate: 26.8 months, high: 47.0 months; <em>p</em> = 0.24) across malnutrition categories. Weight loss was not significantly associated with grade 3 to 4 toxicity (≥5%: 92.0%, &lt;5%: 87.0%; <em>p</em> = 0.73), median progression-free survival (≥5%: 24.0 months, &lt;5%: 15.9 months; <em>p</em> = 0.51) or median OS (≥5%: 30.6 months, &lt;5%: 35.5 months; <em>p</em> = 0.74).</div></div><div><h3>Conclusion</h3><div>Patient-reported nutritional status and weight loss before concurrent chemoradiotherapy were neither associated with toxicity nor survival.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 1","pages":"Article 100764"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971470","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":"Surgery for Patients With cT3/4N2M0, Stage IIIB NSCLC. Is It Time to Redefine Resectability?","authors":"J. Humberto Rodriguez-Quintero MD, MPH ,&nbsp;Rajika Jindani MD, MPH, MS ,&nbsp;Roger Zhu MD ,&nbsp;Isaac Loh ,&nbsp;Mohamed K. Kamel MD ,&nbsp;Anne Montal MD ,&nbsp;Marc Vimolratana MD, MS ,&nbsp;Neel P. Chudgar MD ,&nbsp;Nitin Ohri MD, MS ,&nbsp;Balazs Halmos MD, MS ,&nbsp;Brendon M. Stiles MD","doi":"10.1016/j.jtocrr.2024.100766","DOIUrl":"10.1016/j.jtocrr.2024.100766","url":null,"abstract":"<div><h3>Introduction</h3><div>Chemoradiation followed by durvalumab is considered a standard approach for patients with locally advanced NSCLC. With improvements in perioperative and neoadjuvant approaches, there is renewed interest in offering surgery to carefully selected patients with cT3/4N2 stage IIIB cancer. We sought to assess survival outcomes after surgery as part of a multimodality treatment regimen for these patients.</div></div><div><h3>Methods</h3><div>Patients with cT3/T4N2M0 NSCLC who received surgery (S) as part of a multimodality approach and patients receiving multimodality treatment without surgery (chemoradiation [CRT] or systemic therapy only) were identified in the National Cancer Database (2010–2019). We evaluated factors associated with the receipt of S (logistic regression). After propensity matching, we estimated the overall survival (OS) of patients who received S and compared with those who received CRT (Kaplan-Meier and Cox regression).</div></div><div><h3>Results</h3><div>A total of 44,756 patients were identified, of whom 3928 (8.8%) underwent S, 29,798 (66.6%) CRT, and 11,030 (24.6%) systemic therapy only. Fewer comorbidities (Charlson-Deyo index 0 or 1, adjusted OR [aOR]: 1.22, 95% confidence interval [CI]: 1.05–1.42), treatment at an academic facility (aOR: 1.70, 95% CI: 1.52–1.89), private insurance (aOR: 2.44, 95% CI: 1.61–3.69), adenocarcinoma histology (aOR: 1.48, 95% CI: 1.22–1.79), and clinical T3 stage (&lt;7 cm, aOR: 1.70, 95% CI: 1.53–1.89) were associated with S. In well-balanced, propensity-matched cohorts, patients selected for S had better OS compared with those who underwent CRT (hazard ratio 0.59, 95% CI: 0.56–0.63, <em>p</em> &lt; 0.001) (median OS 49.7 versus 25.0 mo).</div></div><div><h3>Conclusions</h3><div>In this retrospective cohort analysis, patients with cT3/4N2, stage IIIB NSCLC who underwent surgical resection had better OS compared with those patients treated with CRT. Careful patient selection is undoubtedly critical, but stage IIIB designation alone should not exclude patients from surgical consideration.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 1","pages":"Article 100766"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932223","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":"Efficacy and Safety of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting Transforming Growth Factor-β and Programmed Death-Ligand 1, Plus Chemotherapy in Patients With Stage IV NSCLC","authors":"Christian Rolfo MD, PhD ,&nbsp;Laurent Greillier MD, PhD ,&nbsp;Remi Veillon MD, PhD ,&nbsp;Firas Badin MD, MBA ,&nbsp;Francois Ghiringhelli MD, PhD ,&nbsp;Nicolas Isambert MD, PhD ,&nbsp;Astrid Paulus MD, PhD ,&nbsp;Surendra Pal Chaudhary MD ,&nbsp;Yulia Vugmeyster PhD ,&nbsp;Masashi Sato MSc ,&nbsp;Sandrine Hiret MD, PhD","doi":"10.1016/j.jtocrr.2024.100748","DOIUrl":"10.1016/j.jtocrr.2024.100748","url":null,"abstract":"<div><h3>Introduction</h3><div>In a phase 1 study, bintrafusp alfa was found to have an encouraging clinical activity in patients with previously treated advanced NSCLC. This study evaluated the safety and efficacy of bintrafusp alfa with chemotherapy in patients with stage IV NSCLC regardless of the programmed death-ligand 1 (PD-L1) expression status.</div></div><div><h3>Methods</h3><div>In this open-label, phase 1b/2 study (NCT03840915), eligible patients were assigned to one of four cohorts. Patients with previously untreated metastatic NSCLC (cohorts A, B, and C) received bintrafusp alfa with chemotherapy as first-line treatment, whereas patients whose disease progressed on previous treatment with programmed cell death protein 1 or PD-L1 inhibitors (cohort D) received bintrafusp alfa with chemotherapy as second-line treatment. The primary objective of this study was to evaluate the safety and tolerability of bintrafusp alfa with chemotherapy.</div></div><div><h3>Results</h3><div>Four serious and one nonserious treatment-emergent adverse events were considered dose-limiting toxicities, none of which were assessed as related to bintrafusp alfa by the investigator. Any-grade bintrafusp alfa-related adverse events occurred in 20.7% of patients in cohorts A+B+C and in 16.7% of patients in cohort D. Keratoacanthoma was the most common transforming growth factor-β inhibition-mediated skin lesion (cohorts A+B+C: 12.1% and cohort D: 8.3%). In cohorts A+B+C, the overall response rate was 48.3%, and in patients with PD-L1 tumor proportion score of more than or equal to 50.0%, it was 71.4%. On the basis of an interim analysis, the data were considered mature, and no further analysis has been planned.</div></div><div><h3>Conclusion</h3><div>Bintrafusp alfa with chemotherapy was found to have a manageable safety profile and encouraging clinical activity in patients with stage IV NSCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 1","pages":"Article 100748"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881583","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":"Letter Regarding “Radiotherapy Improves Survival in NSCLC After Oligoprogression on Immunotherapy: A Cohort Study”","authors":"Nanami Kosaka MD,&nbsp;Yuki Kataoka MD, MPH, DrPH","doi":"10.1016/j.jtocrr.2024.100760","DOIUrl":"10.1016/j.jtocrr.2024.100760","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 1","pages":"Article 100760"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950776","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":"Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1–Expressing Diffuse Pleural Mesothelioma: A Phase 1 Study","authors":"Prashasti Agrawal MD ,&nbsp;Michael Offin MD ,&nbsp;Victoria Lai MD ,&nbsp;Michelle S. Ginsberg MD ,&nbsp;Prasad S. Adusumilli MD, FACS ,&nbsp;Valerie W. Rusch MD ,&nbsp;Jennifer L. Sauter MD ,&nbsp;Teresa Ho BS ,&nbsp;Phillip Wong PhD ,&nbsp;Marjorie G. Zauderer MD","doi":"10.1016/j.jtocrr.2024.100756","DOIUrl":"10.1016/j.jtocrr.2024.100756","url":null,"abstract":"<div><h3>Introduction</h3><div>WT1 often presents on the surface of diffuse pleural mesotheliomas (DPMs) and is an ideal therapeutic target. Galinpepimut-S (GPS), a tetravalent, non–human leukocyte antigen–restricted, heteroclitic WT1–specific peptide vaccine was safe and effective in early phase clinical trials and upregulates T-cell suppressive programmed death-ligand 1 in the tumor microenvironment of other malignancies. A randomized phase 2 study of adjuvant GPS in patients with DPM trended toward improved median overall survival.</div></div><div><h3>Methods</h3><div>To further enhance immunogenicity, we combined GPS with nivolumab, an anti-PD1 monoclonal antibody, in an open-label, single-center phase 1 study, examining tolerability and immunogenicity in patients with previously treated DPM. We enrolled patients with progressive or recurrent DPM treated with at least one course of pemetrexed-based chemotherapy. Patients received two doses of GPS followed by six doses of GPS with intravenous nivolumab every 2 weeks, and up to six additional cycles until disease progression or unacceptable toxicity.</div></div><div><h3>Results</h3><div>Ten patients were treated; 70% experienced mostly mild treatment-related adverse events; two experienced a grade 3 or higher adverse event. Three of the 10 patients (30%) reported vaccine-specific T-cell responses. There were no partial responses; three patients had prolonged stable disease with up to 17% decrease in tumor volume. Median progression-free survival was 3.9 months and the median overall survival was 7.4 months.</div></div><div><h3>Conclusions</h3><div>Coadministration of GPS and nivolumab reported a tolerable toxicity profile and induced immune responses in a subset of patients, but initial response and survival benefit were limited possibly owing to the small sample size.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 1","pages":"Article 100756"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971456","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}