title: Randomized Phase III Study to Assess Efficacy and Safety of Adjuvant CAPOX with or without Bevacizumab in Patients after Resection of Colorectal Liver Metastases: HEPATICA study.
abstract: Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF). Recurrence after resection of colorectal liver metastases (CRLMs), presumably caused by VEGF-mediated outgrowth of micrometastases, might decrease when VEGF is inhibited. This study examines the efficacy and safety of adding bevacizumab to an adjuvant regimen of CAPOX in patients undergoing radical resection for their CRLMs. Patients with resected CRLMs were randomized after surgery to receive CAPOX and bevacizumab (arm A) or CAPOX alone (arm B) as adjuvant treatment. CAPOX was given in both arms for a total of eight cycles. Bevacizumab was administered for 16 cycles. The primary end point was disease-free survival (DFS). Secondary outcomes were overall survival (OS), toxicity, and quality of life (QoL). In total, 79 patients were randomized. At the time of analysis, 23 events were encountered in arm A and 20 in arm B. One-year DFS rate was 79% [95% confidence interval (CI): 68%-93%] and 68% (95% CI: 55%-85%) for arm A and B, respectively (P=.89). Toxicity was evaluated for 75 patients. No significant differences in toxicity between the two arms were found. QoL scores were higher in arm A, of which emotional functioning and global QoL scores were significant. Adding bevacizumab to a CAPOX regimen in patients undergoing a resection for their CLM is safe and showed higher QoL scores compared with CAPOX alone. Because of premature closure of the study, conclusions about the effect on DFS of additional VEGF inhibition in this setting could not yet be made.
authors.affiliation: Department of Surgical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
authors.forename: Nikol
authors.initials: N
authors.lastname: Snoeren
authors.affiliation: Department of Surgical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
authors.forename: Richard
authors.initials: R
authors.lastname: van Hillegersberg
authors.affiliation: Department of Surgical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
authors.forename: Sander B
authors.initials: SB
authors.lastname: Schouten
authors.affiliation: Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
authors.forename: Andre M
authors.initials: AM
authors.lastname: Bergman
authors.affiliation: Department of Biometrics, The Netherlands Cancer Institute/Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
authors.forename: Erikv
authors.initials: E
authors.lastname: van Werkhoven
authors.affiliation: Department of Biometrics, The Netherlands Cancer Institute/Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
authors.forename: Otilia
authors.initials: O
authors.lastname: Dalesio
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.affiliation: Department of Medical Oncology, VU Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: Henk M
authors.initials: HM
authors.lastname: Verheul
authors.affiliation: Department of Surgery, MC Haaglanden, Lijnbaan 32, 2512 VA, Den Haag.
authors.forename: Joost
authors.initials: J
authors.lastname: van der Sijp
authors.affiliation: Department of Surgical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
authors.forename: Inne H M
authors.initials: IH
authors.lastname: Borel Rinkes
authors.affiliation: Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Electronic address: e.voest@nki.nl.
authors.forename: E E
authors.initials: EE
authors.lastname: Voest
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D000069287:Capecitabine / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011182:Postoperative Care; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000069287:Capecitabine