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 promising activity compared with historical controls. HER2 3+ overexpression and Grb7 positivity are potentially predictive for survival and treatment response, respectively.
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 promising activity compared with historical controls. HER2 3+ overexpression and Grb7 positivity are potentially predictive for survival and treatment response, respectively.
Authors: W Polkowski; J W van Sandick; G J Offerhaus; F J ten Kate; J Mulder; H Obertop; J J van Lanschot Journal: Ann Surg Oncol Date: 1999 Apr-May Impact factor: 5.344
Authors: Maria J Valkema; Bo Jan Noordman; Bas P L Wijnhoven; Manon C W Spaander; Katharina Biermann; Sjoerd M Lagarde; Roel J Bennink; Wendy M J Schreurs; Mark J Roef; Monique G G Hobbelink; Marcel J R Janssen; Laura H Graven; J Jan B van Lanschot; Roelf Valkema Journal: J Nucl Med Date: 2019-03-15 Impact factor: 10.057
Authors: S M Swain; A Schneeweiss; L Gianni; J J Gao; A Stein; M Waldron-Lynch; S Heeson; M S Beattie; B Yoo; J Cortes; J Baselga Journal: Ann Oncol Date: 2017-04-01 Impact factor: 32.976
Authors: Manish A Shah; Yoon-Koo Kang; Peter C Thuss-Patience; Atsushi Ohtsu; Jaffer A Ajani; Eric Van Cutsem; Silke Hoersch; Marie-Laurence Harle-Yge; Sanne Lysbet de Haas Journal: Gastric Cancer Date: 2019-01-31 Impact factor: 7.370
Authors: A M Mandard; F Dalibard; J C Mandard; J Marnay; M Henry-Amar; J F Petiot; A Roussel; J H Jacob; P Segol; G Samama Journal: Cancer Date: 1994-06-01 Impact factor: 6.860
Authors: Mette S van Ramshorst; Erik van Werkhoven; Aafke H Honkoop; Vincent O Dezentjé; Irma M Oving; Ingrid A Mandjes; Inge Kemper; Carolien H Smorenburg; Jacqueline M Stouthard; Sabine C Linn; Gabe S Sonke Journal: Breast Date: 2016-08-05 Impact factor: 4.380
Authors: Marieke Pape; Pauline A J Vissers; Laurens V Beerepoot; Mark I van Berge Henegouwen; Sjoerd M Lagarde; Stella Mook; Markus Moehler; Hanneke W M van Laarhoven; Rob H A Verhoeven Journal: Ther Adv Med Oncol Date: 2022-02-26 Impact factor: 8.168
Authors: Francesco Cellini; Stefania Manfrida; Calogero Casà; Angela Romano; Alessandra Arcelli; Alice Zamagni; Viola De Luca; Giuseppe Ferdinando Colloca; Andrea D'Aviero; Lorenzo Fuccio; Valentina Lancellotta; Luca Tagliaferri; Luca Boldrini; Gian Carlo Mattiucci; Maria Antonietta Gambacorta; Alessio Giuseppe Morganti; Vincenzo Valentini Journal: Cancers (Basel) Date: 2022-01-15 Impact factor: 6.639