JTO Clinical and Research Reports最新文献

{"title":"Spontaneous Bilateral Chylothorax Development During Alectinib Therapy for ALK-Rearranged NSCLC—A Case Report","authors":"Sunanjay Bajaj MD ,&nbsp;Andrew Chow MD, PhD ,&nbsp;Alexander Drilon MD ,&nbsp;Or Kalchiem-Dekel MD","doi":"10.1016/j.jtocrr.2023.100606","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2023.100606","url":null,"abstract":"<div><p>The emergence of spontaneous nonmalignant chylous effusions during treatment with various tyrosine kinase inhibitors (TKIs) has been previously described; however, there have been no prior reports for alectinib. Herein, we report a case of symptomatic bilateral chylothorax during alectinib therapy in a patient with <em>ALK</em>-rearranged lung adenocarcinoma. Although immediate control of symptoms was achieved by placement of bilateral tunneled pleural catheters, the chylothorax ultimately resolved only after alectinib discontinuation and transition to an alternative TKI. This case adds alectinib to the growing list of TKIs that may be associated with the rare emergence of spontaneous, nonmalignant chylous effusions.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364323001492/pdfft?md5=ced86e8f238e47769fe1fb8d3ab48ee0&pid=1-s2.0-S2666364323001492-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138558550","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":"Effectiveness and Safety of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in Pulmonary Sarcomatoid Carcinoma","authors":"Daisuke Hazama MD, PhD ,&nbsp;Kenji Nakahama MD, PhD ,&nbsp;Hiroaki Kodama MD ,&nbsp;Akito Miyazaki MD ,&nbsp;Koichi Azuma MD, PhD ,&nbsp;Yosuke Kawashima MD ,&nbsp;Yuki Sato MD ,&nbsp;Kentaro Ito MD ,&nbsp;Yoshimasa Shiraishi MD ,&nbsp;Keita Miura MD ,&nbsp;Takayuki Takahama MD, PhD ,&nbsp;Satoshi Oizumi MD, PhD ,&nbsp;Yoshinobu Namba MD ,&nbsp;Satoshi Ikeda MD, PhD ,&nbsp;Hiroshige Yoshioka MD, PhD ,&nbsp;Asuka Tsuya MD, PhD ,&nbsp;Yuichiro Yasuda MD, PhD ,&nbsp;Yoshiki Negi MD, PhD ,&nbsp;Ayako Hara MD ,&nbsp;Michihito Toda MD, PhD ,&nbsp;Motoko Tachihara MD, PhD","doi":"10.1016/j.jtocrr.2023.100613","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2023.100613","url":null,"abstract":"<div><h3>Introduction</h3><p>Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung cancer associated with poor prognosis and resistance to conventional chemotherapy. Immune checkpoint inhibitors (ICIs), alone or in combination with chemotherapy, were found to have clinical benefits in PSC in recent studies. Nevertheless, because these studies included a small number of patients owing to disease rarity, larger studies are needed to evaluate the effectiveness and safety of ICI-based therapy for PSC.</p></div><div><h3>Methods</h3><p>This multicenter retrospective study evaluated patients with ICI-naive advanced or metastatic PSC who were treated with ICI-based therapy at 25 hospitals in Japan.</p></div><div><h3>Results</h3><p>A total of 124 patients were evaluated. The overall response rate, median progression-free survival (PFS), and median overall survival (OS) were 59.0%, 10.5 months, and 32.8 months, respectively. The PFS and OS rates at 24 months were 35.3% and 51.5%, respectively. Programmed death-ligand 1 expression, concomitant chemotherapy, and the treatment line were not significantly associated with PFS or OS. Immune-related adverse events (irAEs) were observed in 70 patients (56.5%), including 30 (24.2%) with grade 3 to 5 events. Patients with mild irAEs (grades 1–2) had longer PFS and OS than did those with severe (grades 3–5) or no irAEs. In a multivariate analysis, any-grade irAEs and the absence of liver metastases were independently associated with PFS, whereas any-grade irAEs and Eastern Cooperative Oncology Group performance status less than or equal to 1 were independently associated with OS.</p></div><div><h3>Conclusions</h3><p>ICI-based therapy was found to have promising effectiveness in patients with advanced or metastatic PSC, regardless of programmed death-ligand 1 expression, concomitant chemotherapy, or treatment line.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266636432300156X/pdfft?md5=c5a67e39be20c6b28c57b7fb4a3af524&pid=1-s2.0-S266636432300156X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139050132","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":"The Impact of On-Target Resistance Mediated by EGFR-T790M or EGFR-C797S on EGFR Exon 20 Insertion Mutation Active Tyrosine Kinase Inhibitors","authors":"Ikei S. Kobayashi MD, PhD ,&nbsp;William Shaffer MS ,&nbsp;Hollis Viray MD ,&nbsp;Deepa Rangachari MD ,&nbsp;Paul A. VanderLaan MD, PhD ,&nbsp;Susumu S. Kobayashi MD, PhD ,&nbsp;Daniel B. Costa MD, PhD","doi":"10.1016/j.jtocrr.2023.100614","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2023.100614","url":null,"abstract":"<div><h3>Introduction</h3><p>Mechanisms of resistance to EGFR exon 20 insertion mutation active inhibitors have not been extensively studied in either robust preclinical models or patient-derived rebiopsy specimens. We sought to characterize on-target resistance mutations identified in <em>EGFR</em> exon 20 insertion-mutated lung cancers treated with mobocertinib or poziotinib and evaluate whether these mutations would or would not have cross-resistance to next-generation inhibitors zipalertinib, furmonertinib, and sunvozertinib.</p></div><div><h3>Methods</h3><p>We identified mechanisms of resistance to EGFR exon 20 insertion mutation active inhibitors and then used preclinical models of EGFR exon 20 insertion mutations (A767_V769dupASV, D770_N771insSVD, V773_C774insH) plus common EGFR mutants to probe inhibitors in the absence/presence of EGFR-T790M or EGFR-C797S.</p></div><div><h3>Results</h3><p>Mobocertinib had a favorable therapeutic window in relation to EGFR wild type for EGFR exon 20 insertion mutants, but the addition of EGFR-T790M or EGFR-C797S negated the observed window. Zipalertinib had a favorable therapeutic window for cells driven by EGFR-A767_V769dupASV or EGFR-D770_N771insSVD in the presence or absence of EGFR-T790M. Furmonertinib and sunvozertinib had the most favorable therapeutic windows in the presence or absence of EGFR-T790M in all cells tested. <em>EGFR</em>-C797S in <em>cis</em> to all <em>EGFR</em> mutations evaluated generated dependent cells that were resistant to the covalent EGFR tyrosine kinase inhibitors mobocertinib, zipalertinib, furmonertinib, sunvozertinib, poziotinib, and osimertinib.</p></div><div><h3>Conclusions</h3><p>This report highlights that poziotinib and mobocertinib are susceptible to on-target resistance mediated by <em>EGFR</em>-T790M or -C797S in the background of the most prevalent EGFR exon 20 insertion mutations. Furmonertinib, sunvozertinib, and to a less extent zipalertinib can overcome EGFR-T790M compound mutants, whereas EGFR-C797S leads to covalent inhibitor cross-resistance—robust data that support the limitations of mobocertinib and should further spawn the development of next-generation covalent and reversible EGFR exon 20 insertion mutation active inhibitors with favorable therapeutic windows that are less vulnerable to on-target resistance.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364323001571/pdfft?md5=b29615272c30eeae767ab178a24a2b49&pid=1-s2.0-S2666364323001571-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139050134","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":"HIP1-ALK–Rearranged Lung Cancer in a Young Adult With BRAF V600E Mutation Detected After ALK Tyrosine Kinase Inhibitor Therapy: A Case Report","authors":"Aiko Ogimoto MD,&nbsp;Naoko Katsurada MD, PhD,&nbsp;Atsuhiko Yatani MD,&nbsp;Chihiro Mimura MD,&nbsp;Masatsugu Yamamoto MD, PhD,&nbsp;Motoko Tachihara MD, PhD","doi":"10.1016/j.jtocrr.2023.100612","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2023.100612","url":null,"abstract":"<div><p>HIP1-ALK is a relatively rare fusion pattern in ALK-rearranged NSCLC. Existing studies on the efficacy of ALK tyrosine kinase inhibitor (TKI) resistance mechanisms and treatment strategies in HIP1-ALK–rearranged lung cancer are limited. Here, we report the case of an 18-year-old man with HIP1-ALK–rearranged adenocarcinoma who developed BRAF V600E and V1180L mutations after ALK TKI therapy, in whom the administration of BRAF and MEK inhibitors was ineffective. Brigatinib was effective after chemotherapy with cytotoxic drugs. Development of effective treatments is desirable for rare variants of ALK-rearranged lung cancer after acquiring resistance to ALK TKIs.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364323001558/pdfft?md5=a6b0f6966969f24e8a5f368b3ea208c7&pid=1-s2.0-S2666364323001558-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139050133","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":"Effective Communication About Lung Cancer Screening Without Iatrogenic Stigma: A Brief Report Case Study Using the Lung Cancer Stigma Communications Assessment Tool of LungTalk","authors":"Lisa Carter-Bawa PhD, MPH, APRN, ANP-C, FAAN ,&nbsp;Jamie S. Ostroff PhD ,&nbsp;Kaitlyn Hoover MS ,&nbsp;Jamie L. Studts PhD","doi":"10.1016/j.jtocrr.2023.100585","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2023.100585","url":null,"abstract":"<div><h3>Introduction</h3><p>Stigma thwarts progress in lung cancer risk reduction and control and adversely affects patients across the entire lung cancer care continuum. In developing and disseminating patient and public-facing interventions to increase lung screening, we must be cognizant of how communications have the potential for further stigmatization of at-risk populations. Creation of the Lung Cancer Stigma Communications Assessment Tool (LCS-CAT) version 1 was supported by the American Cancer Society’s National Lung Cancer Roundtable to help content developers identify, remove, and replace potentially stigmatizing language and imagery from materials designed to engage individuals across the lung cancer continuum.</p></div><div><h3>Methods</h3><p>The LCS-CAT considers language, imagery, and context and was used to audit a public-facing health communication and decision support tool called <em>LungTalk</em>.</p></div><div><h3>Results</h3><p>The audit performed by two behavioral scientists revealed multiple issues in all three areas, and specific feedback and alternatives were identified.</p></div><div><h3>Conclusions</h3><p>Applying the LCS-CAT to <em>LungTalk</em> was a productive process that helped remove potentially stigmatizing language and imagery from this tool designed to engage individuals in the process of making an informed decision about lung screening. To support destigmatization of lung cancer, communication creators should consider a stigma biopsy on all public-facing campaigns for lung screening to help identify, eliminate, and replace messages that could compromise engagement with the lung cancer screening opportunity.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364323001285/pdfft?md5=9601ad4a3ef44513172920434b0b7355&pid=1-s2.0-S2666364323001285-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92043277","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":"Clinical Trial and Real-World Outcomes of Patients With Metastatic NSCLC in the Post-Platinum–Based Chemotherapy Failure Setting","authors":"Yu Yang Soon MBBS ,&nbsp;Wesley Furnback BA ,&nbsp;Jin Kim MS ,&nbsp;Po-Ya Chuang MHA ,&nbsp;Gordon Chavez BA ,&nbsp;Christina Proescholdt MD ,&nbsp;Cloe Ying Chee Koh MS","doi":"10.1016/j.jtocrr.2023.100579","DOIUrl":"10.1016/j.jtocrr.2023.100579","url":null,"abstract":"<div><h3>Introduction</h3><p>A literature review was undertaken to identify clinical trials and real-world studies of patients with stage IV NSCLC who had progressed on or after treatment with platinum-based chemotherapy.</p></div><div><h3>Methods</h3><p>The EMBASE and MEDLINE databases were used to search for English-language studies published between September 28, 2017, and September 28, 2021. Studies were included in the review if they (1) were clinical trials or real-world analyses of one or more treatment regimens for patients with stage IV NSCLC who had progressed on or after treatment with platinum-based chemotherapy, (2) contained an end point including efficacy, effectiveness, or safety, and (3) included 45 or more patients.</p></div><div><h3>Results</h3><p>In total, there were 15 publications (nine unique trials and three real-world studies) included. Sample size ranged from 49 to 1253 patients. At least one treatment arm in eight of the nine clinical trials reported an overall response rate of ≥15%. Median progression-free survival (PFS) and overall survival ranged from 1.9 to 5.2 months and 5.4 to 15.4 months in clinical trials and 4.4 to 6.8 months and 8.3 to 18.0 months in real-world studies, respectively. Within studies reporting median PFS, a median PFS of more than or equal to 3 months was reported in eight of 11 clinical trials and both real-world studies. Discontinuation due to adverse events ranged from 1.9% to 18% across all included studies.</p></div><div><h3>Conclusions</h3><p>Patients with stage IV NSCLC had limited response and a high burden of adverse events during treatment after progression on platinum-containing chemotherapy. There remains a pressing unmet need for additional, effective, and tolerable treatment options in this setting.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71521886","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":"Repotrectinib Overcomes F2004V Resistance Mutation in ROS1-Rearranged NSCLC: A Case Report","authors":"Elio Gregory Pizzutilo MD ,&nbsp;Alberto Giuseppe Agostara MD ,&nbsp;Laura Roazzi MD ,&nbsp;Rebecca Romanò MD ,&nbsp;Valentina Motta PhD ,&nbsp;Calogero Lauricella PhD ,&nbsp;Giovanna Marrapese PhD ,&nbsp;Giulio Cerea MD ,&nbsp;Diego Signorelli MD, PhD ,&nbsp;Silvio Marco Veronese PhD ,&nbsp;Laura Giuseppina Giannetta MD ,&nbsp;Andrea Sartore-Bianchi MD ,&nbsp;Salvatore Siena MD","doi":"10.1016/j.jtocrr.2023.100555","DOIUrl":"10.1016/j.jtocrr.2023.100555","url":null,"abstract":"<div><p>ROS1 tyrosine kinase inhibitors (TKIs) were found to provide a substantial clinical benefit for patients with advanced ROS1-positive (ROS1+) NSCLC. Nevertheless, TKI resistance inevitably develops with different mechanisms, preventing prolonged responses. For this reason, next-generation compounds are under clinical development. ROS1 F2004 substitutions have been previously detected on circulating tumor DNA of patients progressing to entrectinib. Hereby, we report the case of a patient with ROS1+ NSCLC in which F2004V-acquired mutation was detected on a site of disease progression, after entrectinib and crizotinib failure. A subsequent treatment with next-generation TKI repotrectinib led to disease response, providing the first clinical evidence of activity of repotrectinib against F2004V resistance mutation.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266636432300098X/pdfft?md5=cb2e257dc0f7c9a2548efebc9427216f&pid=1-s2.0-S266636432300098X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45263817","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":"Real-World Evidence of EGFR Targeted Therapy in NSCLC– A Brief Report of Decade Long Single Center Experience","authors":"Anuradha Chougule PhD ,&nbsp;Pratik Chandrani PhD ,&nbsp;Vanita Noronha MD, DM ,&nbsp;Priyanka Pange BSc ,&nbsp;Shrutikaa Kale MSc ,&nbsp;Ankita Nikam MSc ,&nbsp;Kavya Nambiar MSc ,&nbsp;Dipika Marchande BSc ,&nbsp;Arpana Durve BSc ,&nbsp;Vinod Gupta BSc ,&nbsp;Vinita Jagtap MSc ,&nbsp;Priyanka Tiwrekar BA ,&nbsp;Nandini Menon MD, DM ,&nbsp;Amit Joshi MD, DM ,&nbsp;Rajeev Kaushal MD ,&nbsp;Trupti Pai MD ,&nbsp;Vijay Maruti Patil MD, DM ,&nbsp;Amit Dutt PhD ,&nbsp;Shripad Dinanath Banavali MD ,&nbsp;Kumar Prabhash MD, DM","doi":"10.1016/j.jtocrr.2023.100566","DOIUrl":"10.1016/j.jtocrr.2023.100566","url":null,"abstract":"<div><p>The significance of EGFR targeted therapy in the lung adenocarcinoma is paramount. Several controlled clinical trials have reported considerable survival of EGFR mutation positive patients on receiving the EGFR tyrosine kinase inhibitor (TKI). However, the real-world evidence of benefits of EGFR TKI would be further useful to understand how the designated therapeutic regimen benefits the patients. In this study, we report a decade long real-world evidence of EGFR molecular testing in lung cancer at Tata Memorial Hospital (Mumbai, India). Laboratory and hospital records containing basic demographic details, clinical characteristics, treatment regimen, survival outcome were collected retrospectively. Statistical association and survival analysis were performed using the R programming. The cohort includes 9,053 lung cancer patients tested for EGFR mutations during 2011 to 2019. Baseline T790M and compound mutations were the only mutations observed co-occurring while all other EGFR mutations were mutually exclusive. Furthermore, the baseline T790M were also observed to be associated with TTF1 positivity, smoking and local metastasis. Overall survival of the patients harboring co-occurring compound mutations was significantly lesser than the other EGFR positive patients. Overall, our study suggests that EGFR TKI may provide real-world benefit to the lung cancer patients harboring mutually exclusive EGFR mutations. On the other hand, further systematic study is essential to develop better therapeutic regimen for co-occurring baseline EGFR T790M and other compound mutations.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364323001091/pdfft?md5=6b1ba7c080a5b450f88bea1968aa239e&pid=1-s2.0-S2666364323001091-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41551652","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":"Pneumonitis During Durvalumab Consolidation Therapy Affects Survival in Stage III NSCLC","authors":"Yuhei Kinehara MD, PhD ,&nbsp;Takayuki Shiroyama MD, PhD ,&nbsp;Akihiro Tamiya MD ,&nbsp;Motohiro Tamiya MD ,&nbsp;Seigo Minami MD, PhD ,&nbsp;Masaki Kanazu MD ,&nbsp;Osamu Morimura MD, PhD ,&nbsp;Toshie Niki MD, PhD ,&nbsp;Satoshi Tetsumoto MD, PhD ,&nbsp;Yoshihiko Taniguchi MD ,&nbsp;Tomoki Kuge MD ,&nbsp;Kazumi Nishino MD, PhD ,&nbsp;Izumi Nagatomo MD, PhD ,&nbsp;Atsushi Kumanogoh MD, PhD ,&nbsp;Isao Tachibana MD, PhD","doi":"10.1016/j.jtocrr.2023.100586","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2023.100586","url":null,"abstract":"<div><h3>Introduction</h3><p>Durvalumab consolidation therapy is the standard of care after concurrent chemoradiotherapy (CRT) for stage III NSCLC. Immune-related pneumonitis during durvalumab treatment is potentially fatal; however, information is lacking regarding the impact of pneumonitis on patient survival. This study investigates the effect of pulmonary and nonpulmonary immune-related adverse events (irAEs) on the efficacy of durvalumab treatment in patients with stage III NSCLC.</p></div><div><h3>Methods</h3><p>We retrospectively assessed 158 patients who received durvalumab after CRT at nine Japanese institutions between July 2018 and March 2020. Survival outcomes were compared between patients who developed pneumonitis with those who developed irAEs other than pneumonitis. Patients who survived for less than 3 months were excluded to reduce immortal time bias.</p></div><div><h3>Results</h3><p>Among 158 evaluated patients, 76 (48%) experienced grade less than or equal to one irAEs, whereas 82 (52%) experienced grade greater than or equal to two irAEs. Among the patients with grade greater than or equal to two irAEs, those with grade greater than or equal to two pneumonitis (n = 55) were compared with those with grade greater than or equal to two irAEs other than pneumonitis (n = 27). Patients with grade greater than or equal to two pneumonitis exhibited a significantly worse overall survival than those with grade greater than or equal to two irAEs that excluded pneumonitis. Multivariate analysis revealed that grade greater than or equal to two pneumonitis (hazard ratio = 3.71; 95% confidence interval, 1.85–7.45; <em>p</em> &lt; 0.001) and squamous histology (hazard ratio = 2.64; 95% confidence interval, 1.29–5.42; <em>p</em> = 0.008) were independently associated with worse overall survival.</p></div><div><h3>Conclusions</h3><p>After minimizing immortal time bias, pneumonitis grade two or greater and squamous histology were poor prognostic factors in patients who received consolidation durvalumab after CRT.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364323001297/pdfft?md5=86be53236184c9947175962624c86cff&pid=1-s2.0-S2666364323001297-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91986812","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":"Patient-Reported Health-Related Quality of Life in KEYNOTE-604: Pembrolizumab or Placebo Added to Etoposide and Platinum as First-Line Therapy for Extensive-Stage SCLC","authors":"Hye Ryun Kim MD, PhD ,&nbsp;Mark M. Awad MD, PhD ,&nbsp;Alejandro Navarro MD ,&nbsp;Maya Gottfried MD ,&nbsp;Solange Peters MD, PhD ,&nbsp;Tibor Csőszi MD ,&nbsp;Parneet K. Cheema MD ,&nbsp;Delvys Rodriguez-Abreu MD, PhD ,&nbsp;Mirjana Wollner MD ,&nbsp;James Chih-Hsin Yang MD, PhD ,&nbsp;Julien Mazieres MD, PhD ,&nbsp;Francisco J. Orlandi MD ,&nbsp;Alexander Luft MD, PhD ,&nbsp;Mahmut Gümüş MD ,&nbsp;Terufumi Kato MD ,&nbsp;Gregory P. Kalemkerian MD ,&nbsp;Yiwen Luo PhD ,&nbsp;Melissa L. Santorelli PhD, MPH ,&nbsp;M. Catherine Pietanza MD ,&nbsp;Charles M. Rudin MD, PhD","doi":"10.1016/j.jtocrr.2023.100572","DOIUrl":"10.1016/j.jtocrr.2023.100572","url":null,"abstract":"<div><h3>Introduction</h3><p>In the phase 3 KEYNOTE-604 study (NCT03066778), pembrolizumab plus etoposide and platinum chemotherapy (EP) significantly (<em>p</em> = 0.0023) improved progression-free survival versus placebo plus EP in previously untreated extensive-stage SCLC (ES-SCLC). We present health-related quality of life (HRQoL) results from KEYNOTE-604.</p></div><div><h3>Methods</h3><p>Patients with stage IV SCLC were randomized 1:1 to pembrolizumab 200 mg or placebo every 3 weeks for 35 cycles plus four cycles of EP. Secondary end points included mean change from baseline to week 18 in the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire—Core 30 (QLQ-C30) global health status/quality of life (GHS/QoL) scale and time to deterioration in the composite outcome of cough, chest pain, or dyspnea from QLQ-C30 and QLQ—Lung Cancer Module 13. Two-sided, nominal <em>p</em> values are reported.</p></div><div><h3>Results</h3><p>A total of 439 patients completed at least one QLQ-C30 and QLQ—Lung Cancer Module 13 assessment (pembrolizumab + EP, n = 221; placebo + EP, n = 218). GHS/QoL scores improved from baseline to week 18: least squares mean (95% confidence interval [CI]) changes were 8.7 (5.3–12.1) for pembrolizumab plus EP and 4.2 (0.9–7.5) for placebo plus EP. Between-group differences in least squares mean scores were improved for pembrolizumab plus EP (4.4 [95% CI: 0.2–8.7], <em>p</em> = 0.040]). Median time to deterioration for the composite end point was not reached and 8.7 (95% CI: 5.9–not reached) months, respectively (hazard ratio = 0.80 [95% CI: 0.56–1.14], <em>p</em> = 0.208).</p></div><div><h3>Conclusions</h3><p>First-line pembrolizumab plus EP therapy maintained HRQoL in patients with ES-SCLC and may be associated with greater improvement than placebo plus EP. Together with the efficacy and safety findings in KEYNOTE-604, HRQoL data support the benefit of pembrolizumab in ES-SCLC.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89718736","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}