Inna M Chen, Julia S Johansen, Susann Theile, Libbie M Silverman, Katherine R Pelz, Kasper Madsen, Olav Dajani, Kevin Z M Lim, Torben Lorentzen, Omnia Gaafer, Leonidas G Koniaris, Anna C Ferreira, Brian Neelon, Denis C Guttridge, Michael C Ostrowski, Teresa A Zimmers, Dorte Nielsen
{"title":"nab -紫杉醇和吉西他滨联合或不联合Tocilizumab作为一线治疗晚期胰腺癌的随机II期研究：生存和恶病质。","authors":"Inna M Chen, Julia S Johansen, Susann Theile, Libbie M Silverman, Katherine R Pelz, Kasper Madsen, Olav Dajani, Kevin Z M Lim, Torben Lorentzen, Omnia Gaafer, Leonidas G Koniaris, Anna C Ferreira, Brian Neelon, Denis C Guttridge, Michael C Ostrowski, Teresa A Zimmers, Dorte Nielsen","doi":"10.1200/JCO.23.01965","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>This randomized phase-II trial (ClinicalTrials.gov identifier: NCT02767557) compared efficacy of gemcitabine/nab-paclitaxel (Gem/Nab) with or without the anti-interleukin-6 (IL-6) receptor antibody tocilizumab (Toc) for advanced pancreatic cancer (PC).</p><p><strong>Methods: </strong>A safety cohort received Gem 1,000 mg/m<sup>2</sup> and Nab 125 mg/m<sup>2</sup> on days 1, 8, and 15, and Toc 8 mg/kg on day 1 for each 28-day cycle. Participants with modified Glasgow prognostic scores of 1 or 2 were randomly assigned 1:1 to receive Gem/Nab/Toc or Gem/Nab. The primary end point was the overall survival (OS) rate at 6 months (OS6). Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. Exploratory end points were cachexia, quality of life, and biomarkers, including the cachexia-promoting protein, growth differentiation factor 15 (GDF15).</p><p><strong>Results: </strong>Overall, 147 patients were treated, including six safety cohort participants. The median follow-up period was 8.1 months (IQR, 4.2-13.9). OS6 was 68.6% (95% CI, 56.3 to 78.1) for the Gem/Nab/Toc group and 62.0% (49.6-72.1) for the Gem/Nab group (<i>P</i> = .409). OS for Gem/Nab/Toc versus Gem/Nab improved at 18 months (27.1% <i>v</i> 7.0%, <i>P</i> = .001). No differences in median OS, PFS, or ORR were observed. Incidence of grade-3+ treatment-related adverse events (TrAEs) was 88.1% for Gem/Nab/Toc and 63.4% for Gem/Nab (<i>P</i> < .001). Gem/Nab/Toc decreased muscle loss versus Gem/Nab, with median change +0.1013% versus -3.430% (<i>P</i> = .0012) at 2 months and +0.7044 versus -3.353% (<i>P</i> = .036) at 4 months. Incidence of muscle loss was 43.48% on Gem/Nab/Toc versus 73.52% on Gem/Nab at 2 months (<i>P</i> = .0045) and 41.82% versus 68.75% (<i>P</i> = .0062) at 4 months. GDF15 was not changed by Gem/Nab or Gem/Nab/Toc.</p><p><strong>Conclusion: </strong>Although the primary end point was not met and TrAEs were increased by Toc, increased survival at 18 months and reduced muscle wasting support an anticachexia effect of IL-6 blockade independent of GDF15. Further studies could leverage these findings for precision anticachexia therapy.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2301965"},"PeriodicalIF":42.1000,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia.\",\"authors\":\"Inna M Chen, Julia S Johansen, Susann Theile, Libbie M Silverman, Katherine R Pelz, Kasper Madsen, Olav Dajani, Kevin Z M Lim, Torben Lorentzen, Omnia Gaafer, Leonidas G Koniaris, Anna C Ferreira, Brian Neelon, Denis C Guttridge, Michael C Ostrowski, Teresa A Zimmers, Dorte Nielsen\",\"doi\":\"10.1200/JCO.23.01965\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>This randomized phase-II trial (ClinicalTrials.gov identifier: NCT02767557) compared efficacy of gemcitabine/nab-paclitaxel (Gem/Nab) with or without the anti-interleukin-6 (IL-6) receptor antibody tocilizumab (Toc) for advanced pancreatic cancer (PC).</p><p><strong>Methods: </strong>A safety cohort received Gem 1,000 mg/m<sup>2</sup> and Nab 125 mg/m<sup>2</sup> on days 1, 8, and 15, and Toc 8 mg/kg on day 1 for each 28-day cycle. Participants with modified Glasgow prognostic scores of 1 or 2 were randomly assigned 1:1 to receive Gem/Nab/Toc or Gem/Nab. The primary end point was the overall survival (OS) rate at 6 months (OS6). Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. Exploratory end points were cachexia, quality of life, and biomarkers, including the cachexia-promoting protein, growth differentiation factor 15 (GDF15).</p><p><strong>Results: </strong>Overall, 147 patients were treated, including six safety cohort participants. The median follow-up period was 8.1 months (IQR, 4.2-13.9). OS6 was 68.6% (95% CI, 56.3 to 78.1) for the Gem/Nab/Toc group and 62.0% (49.6-72.1) for the Gem/Nab group (<i>P</i> = .409). OS for Gem/Nab/Toc versus Gem/Nab improved at 18 months (27.1% <i>v</i> 7.0%, <i>P</i> = .001). No differences in median OS, PFS, or ORR were observed. Incidence of grade-3+ treatment-related adverse events (TrAEs) was 88.1% for Gem/Nab/Toc and 63.4% for Gem/Nab (<i>P</i> < .001). Gem/Nab/Toc decreased muscle loss versus Gem/Nab, with median change +0.1013% versus -3.430% (<i>P</i> = .0012) at 2 months and +0.7044 versus -3.353% (<i>P</i> = .036) at 4 months. Incidence of muscle loss was 43.48% on Gem/Nab/Toc versus 73.52% on Gem/Nab at 2 months (<i>P</i> = .0045) and 41.82% versus 68.75% (<i>P</i> = .0062) at 4 months. GDF15 was not changed by Gem/Nab or Gem/Nab/Toc.</p><p><strong>Conclusion: </strong>Although the primary end point was not met and TrAEs were increased by Toc, increased survival at 18 months and reduced muscle wasting support an anticachexia effect of IL-6 blockade independent of GDF15. Further studies could leverage these findings for precision anticachexia therapy.</p>\",\"PeriodicalId\":15384,\"journal\":{\"name\":\"Journal of Clinical Oncology\",\"volume\":\" \",\"pages\":\"JCO2301965\"},\"PeriodicalIF\":42.1000,\"publicationDate\":\"2025-05-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/JCO.23.01965\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/JCO.23.01965","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia.
Purpose: This randomized phase-II trial (ClinicalTrials.gov identifier: NCT02767557) compared efficacy of gemcitabine/nab-paclitaxel (Gem/Nab) with or without the anti-interleukin-6 (IL-6) receptor antibody tocilizumab (Toc) for advanced pancreatic cancer (PC).
Methods: A safety cohort received Gem 1,000 mg/m2 and Nab 125 mg/m2 on days 1, 8, and 15, and Toc 8 mg/kg on day 1 for each 28-day cycle. Participants with modified Glasgow prognostic scores of 1 or 2 were randomly assigned 1:1 to receive Gem/Nab/Toc or Gem/Nab. The primary end point was the overall survival (OS) rate at 6 months (OS6). Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. Exploratory end points were cachexia, quality of life, and biomarkers, including the cachexia-promoting protein, growth differentiation factor 15 (GDF15).
Results: Overall, 147 patients were treated, including six safety cohort participants. The median follow-up period was 8.1 months (IQR, 4.2-13.9). OS6 was 68.6% (95% CI, 56.3 to 78.1) for the Gem/Nab/Toc group and 62.0% (49.6-72.1) for the Gem/Nab group (P = .409). OS for Gem/Nab/Toc versus Gem/Nab improved at 18 months (27.1% v 7.0%, P = .001). No differences in median OS, PFS, or ORR were observed. Incidence of grade-3+ treatment-related adverse events (TrAEs) was 88.1% for Gem/Nab/Toc and 63.4% for Gem/Nab (P < .001). Gem/Nab/Toc decreased muscle loss versus Gem/Nab, with median change +0.1013% versus -3.430% (P = .0012) at 2 months and +0.7044 versus -3.353% (P = .036) at 4 months. Incidence of muscle loss was 43.48% on Gem/Nab/Toc versus 73.52% on Gem/Nab at 2 months (P = .0045) and 41.82% versus 68.75% (P = .0062) at 4 months. GDF15 was not changed by Gem/Nab or Gem/Nab/Toc.
Conclusion: Although the primary end point was not met and TrAEs were increased by Toc, increased survival at 18 months and reduced muscle wasting support an anticachexia effect of IL-6 blockade independent of GDF15. Further studies could leverage these findings for precision anticachexia therapy.
期刊介绍：
The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.
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