Abstract 2735
Background
The AVANT study did not demonstrate disease-free survival (DFS) benefit of the addition of bevacizumab to oxaliplatin-based chemotherapy in stage III resected CC and suggested a potential detrimental effect on overall survival (OS) (A. de Gramont et al. Lancet Oncol. 2012). Here, we present the results of the AVANT study for stage II CC patients.
Methods
The primary endpoint of AVANT was DFS for stage III disease. As an exploratory measure, AVANT also included high-risk stage II CC defined by T4, bowel obstruction or perforation, blood and/or lymphatic vascular invasion and/or perineural invasion, age <50 years, less than 12 nodes analyzed. OS and DFS were estimated by the Kaplan Meier method and compared by log-rank test and Cox regression model.
Results
573 patients had stage II CC (arm A: FOLFOX4, n = 192; arm B: FOLFOX4-bevacizumab, n = 194; arm C: XELOX-bevacizumab, n = 187), of whom 38 (19.8%) in arm A, 36 (18.6%) in arm B, and 40 (21.4%) in arm C had relapsed, developed a new CC, or died after a median follow-up of 6.86 years (IQR: 6.13-11.34). The DFS hazard-ratio was 0.94 (95% CI 0.59-1.48; P = 0.78) for arm B vs arm A and 1.07 (95% CI 0.69-1.67; P = 0.76) for arm C vs arm A. The OS hazard ratio was 0.92 (95% CI 0.55-1.55; P = 0.76) for arm B vs arm A and 0.85 (95% CI 0·50-1.44; P = 0.55) for arm C vs arm A. Safety data of stage II and stage III CC have been reported previously. In multivariable analysis, T4 vs T3-1 (P = 0.041), number of examined nodes (P = 0.005), and age (P = 0.0008) were prognostic for DFS. The 3-year DFS and 5-year OS rates of stage II were 88.2% (95% CI 83.7%-93.0%) and 89.7% (95% CI 85.4%-94.2%) in arm A, 86.6% (95% CI 81.8%-91.6%) and 89.7% (95% CI 85.4%-94.2%) in arm B, 86.7% (95% CI 81.8%-91.8%) and 93.2% (95% CI 89.6%-97.0%) in arm C, respectively.
Conclusions
In this exploratory analysis, bevacizumab did not prolong DFS and OS when added to adjuvant oxaliplatin-based chemotherapy in resected high-risk stage II patients with CC.
Clinical trial identification
NCT00112918.
Editorial acknowledgement
Magdalena Benetkiewicz (GERCOR).
Legal entity responsible for the study
GERCOR.
Funding
Roche.
Disclosure
A. De Gramont: Honoraria (self): Yakult; Honoraria (self): Chugai Pharma. T.W. Kim: Research grant / Funding (self): Merck Serono; Research grant / Funding (self): Pfizer; Research grant / Funding (self): AstraZeneca. J. Gallego-Plazas: Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy: Roche; Advisory / Consultancy: Bayer; Advisory / Consultancy: Lilly; Advisory / Consultancy: Celgene; Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: Novartis; Leadership role, Study Coordinator of Agamenon study in advanced gastric cancer: Agamenon study. A. Cervantes: Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): Servier; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): Roche Beigene; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Foundation Medicine; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Fibrogen; Research grant / Funding (institution): Amcure; Research grant / Funding (institution): Sierra Oncology; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Medimmune; Research grant / Funding (institution): BMS; Research grant / Funding (institution): MSD; Leadership role, Executive Board member of ESMO: not remunerated Chair of Education of ESMO: not remunerated General and Scientific Director of INCLIVA: not remunerated Associate Editor of ESMO Open: not remunerated Associate Editor of Annals of Oncology: remunerated Editor in Chief of Cancer Treatment Reviews: remunerated: Executive Board member of ESMO: not remunerated Chair of Education of ESMO: not remunerated General and Scientific Director of INCLIVA: not remunerated Associate Editor of ESMO Open: not remunerated Associate Editor of Annals of Oncology: remunerated. D.J. Jonker: Research grant / Funding (institution): Hoffman-La Roche; Non-remunerated activity/ies, Chair of the GI Disease Site Committee of the Canadian Cancer Trials Group: Canadian Cancer Trials Group. A. Dewdney: Honoraria (self), Chairing evening meetings: Servier; Honoraria (self): Roche. T. (Sirisingha) Dejthevaporn: Honoraria (self): Roche; Honoraria (self): Eisai; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Eli Lilly; Leadership role: Thai Society of Clinical Oncology (TSCO). M. Moehler: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche. T. André: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD Oncology; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Ventana; Honoraria (self): Sanofi; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self): Chugai; Honoraria (self): Yakult; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: HalioDx. All other authors have declared no conflicts of interest.
Resources from the same session
2674 - Multicenter Phase I Trial of Trastuzumab Emtansine (T-DM1) in Combination with Non-Pegylated Liposomal Doxorubicin (NPLD) in HER2[+] Metastatic Breast Cancer (MBC). THELMA Study
Presenter: Elena López-Miranda
Session: Poster Display session 2
Resources:
Abstract
1398 - Phase 1 study of liposomal formulation of eribulin (E7389-LF) in patients (pts) with advanced solid tumors: primary results of dose-escalation part
Presenter: Noboru Yamamoto
Session: Poster Display session 2
Resources:
Abstract
5818 - Polo-like Kinase 1 inhibitor onvansertib synergizes with paclitaxel in breast cancer carrying p53 mutation
Presenter: Antonio Giordano
Session: Poster Display session 2
Resources:
Abstract
5927 - Phase 1b study of heat shock protein 90 inhibitor, onalespib in combination with paclitaxel in patients with advanced, triple negative breast cancer (NCT02474173).
Presenter: Robert Wesolowski
Session: Poster Display session 2
Resources:
Abstract
1695 - Impact of pertuzumab and T-DM1 on prognosis of HER2-positive metastatic breast cancer (MBC) and factors affecting their efficacy: results from the AGMT_MBC-Registry
Presenter: Simon Peter Gampenrieder
Session: Poster Display session 2
Resources:
Abstract
1742 - Clinical profile and outcome of HER2 positive breast cancer patients with brain metastases treated with HER2 targeted therapy: Real world experience.
Presenter: Prabhat Bhargava
Session: Poster Display session 2
Resources:
Abstract
1846 - Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer: results of single arm phase IV COMACHI study
Presenter: Norikazu Masuda
Session: Poster Display session 2
Resources:
Abstract
5385 - Anti HER-2 Therapies and Left Ventricular Dysfunction The Renaissance Study
Presenter: ANDRES DANIELE
Session: Poster Display session 2
Resources:
Abstract
3320 - Safety and efficacy of T-DM1 in 128 patients with advanced HER2+ breast cancer: The Royal Marsden experience.
Presenter: Nicolò Battisti
Session: Poster Display session 2
Resources:
Abstract
4540 - Use of trastuzumab emtansine (T-DM1; K) after pertuzumab + trastuzumab (PH) in patients with HER2-positive metastatic breast cancer (mBC): challenges in assessing effectiveness of treatment sequencing in the real world (RW)
Presenter: Thibaut Sanglier
Session: Poster Display session 2
Resources:
Abstract