Academic Journal
Phase II Feasibility and Biomarker Study of Neoadjuvant Trastuzumab and Pertuzumab With Chemoradiotherapy for Resectable Human Epidermal Growth Factor Receptor 2-Positive Esophageal Adenocarcinoma:TRAP Study
| العنوان: | Phase II Feasibility and Biomarker Study of Neoadjuvant Trastuzumab and Pertuzumab With Chemoradiotherapy for Resectable Human Epidermal Growth Factor Receptor 2-Positive Esophageal Adenocarcinoma:TRAP Study |
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| المؤلفون: | Stroes, Charlotte I, Schokker, Sandor, Creemers, Aafke, Molenaar, Remco J, Hulshof, Maarten C C M, van der Woude, Stephanie O, Bennink, Roel J, Mathôt, Ron A A, Krishnadath, Kausilia K, Punt, Cornelis J A, Verhoeven, Rob H A, van Oijen, Martijn G H, Creemers, Geert-Jan, Nieuwenhuijzen, Grard A P, van der Sangen, Maurice J C, Beerepoot, Laurens V, Heisterkamp, Joos, Los, Maartje, Slingerland, Marije, Cats, Annemieke, Hospers, Geke A P, Bijlsma, Maarten F, van Berge Henegouwen, Mark I, Meijer, Sybren L, van Laarhoven, Hanneke W M |
| المصدر: | Stroes , C I , Schokker , S , Creemers , A , Molenaar , R J , Hulshof , M C C M , van der Woude , S O , Bennink , R J , Mathôt , R A A , Krishnadath , K K , Punt , C J A , Verhoeven , R H A , van Oijen , M G H , Creemers , G-J , Nieuwenhuijzen , G A P , van der Sangen , M J C , Beerepoot , L V , Heisterkamp , J , Los , M , Slingerland .... |
| سنة النشر: | 2020 |
| المجموعة: | University of Groningen research database |
| الوصف: | PURPOSE: Approximately 15% to 43% of esophageal adenocarcinomas (EACs) are human epidermal growth factor receptor 2 (HER2) positive. Because dual-agent HER2 blockade demonstrated a survival benefit in breast cancer, we conducted a phase II feasibility study of trastuzumab and pertuzumab added to neoadjuvant chemoradiotherapy (nCRT) in patients with EAC. PATIENTS AND METHODS: Patients with resectable HER2-positive EAC received standard nCRT with carboplatin and paclitaxel and 41.4 Gy of radiotherapy, with 4 mg/kg of trastuzumab on day 1, 2 mg/kg per week during weeks 2 to 6, and 6 mg/kg per week during weeks 7, 10, and 13 and 840 mg of pertuzumab every 3 weeks. The primary end point was feasibility, defined as ≥ 80% completion of treatment with both trastuzumab and pertuzumab. An exploratory comparison of survival with a propensity score-matched cohort receiving standard nCRT was performed, as were exploratory pharmacokinetic and biomarker analyses. RESULTS: Of the 40 enrolled patients (78% men; median age, 63 years), 33 (83%) completed treatment with trastuzumab and pertuzumab. No unexpected safety events were observed. R0 resection was achieved in all patients undergoing surgery, with pathologic complete response in 13 patients (34%). Three-year progression-free and overall survival (OS) were 57% and 71%, respectively (median follow-up, 32.1 months). Compared with the propensity score-matched cohort, a significantly longer OS was observed with HER2 blockade (hazard ratio, 0.58; 95% CI, 0.34 to 0.97). Results of pharmacokinetic analysis and activity on [18F]fluorodeoxyglucose positron emission tomography scans did not correlate with survival or pathologic response. Patients with HER2 3+ overexpression or growth factor receptor-bound protein 7 (Grb7) -positive tumors at baseline demonstrated significantly better survival (P = .007) or treatment response (P = .016), respectively. CONCLUSION: Addition of trastuzumab and pertuzumab to nCRT in patients with HER2-positive EAC is feasible and demonstrates potentially ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.1200/JCO.19.01814 |
| الاتاحة: | https://hdl.handle.net/11370/70f51caa-0851-4e66-aad2-cb210dc4b0f0 https://research.rug.nl/en/publications/70f51caa-0851-4e66-aad2-cb210dc4b0f0 https://doi.org/10.1200/JCO.19.01814 https://pure.rug.nl/ws/files/119584475/jco.19.01814.pdf |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.D5D10298 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1200/JCO.19.01814 |
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