352O - Efficacy and safety of maintenance bevacizumab (BEV) with or without capecitabine (CAP) after initial first-line BEV plus docetaxel (DOC) for HER2-...

Date 28 September 2014
Event ESMO 2014
Session Breast cancer, metastatic
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Joseph Gligorov
Citation Annals of Oncology (2014) 25 (suppl_4): iv116-iv136. 10.1093/annonc/mdu329
Authors J. Gligorov1, D.C. Doval2, J. Bines3, Z.F. Jiang4, E. Alba-Conejo5, P.A. Cortes6, S. Srock7, S. de Ducla7, U. Freudensprung8, G. Mustacchi9
  • 1Oncologie Medicale, APHP, CancerEst, Tenon University Hospital, 75020 - Paris/FR
  • 2Medical Oncology, Rajiv Gandhi Cancer Instituteand Research Centre, IN-110085 - New Delhi/IN
  • 3Medical Oncology, Instituto Nacional de Cancer, 20560-120 - Rio de Janeiro/BR
  • 4Medical Oncology, Beijing 307 Hospital of PLA, 100071 - Beijing/CN
  • 5Oncology, HOSPITAL UNIVERSITARIO VIRGEN DE LA VICTORIA, 29010 - MALAGA/ES
  • 6Medical Oncology, Centro Hospitalar Lisboa Norte - Hospital Sta Maria(HSM-CHLN), PT-1649-035 - Lisbon/PT
  • 7Medical Affairs, F Hoffman-La Roche Ltd, Basel/CH
  • 8Global Medical Affairs Biometrics, F Hoffmann-La Roche Ltd, 4070 - Basel/CH
  • 9Docente Di Oncologia Medica, Centro Oncologico ASS1 Triestina, Università di Trieste, 34100 - Trieste/IT

Abstract

Aim

Until regulatory withdrawal of BEV–DOC in 2011, the combination was considered a valid first-line option for HER2-negative mBC based on results of a phase III trial [Miles, JCO 2010]. Progression-free survival (PFS) and response rate (RR) with first-line DOC (max 9 cycles) were significantly improved by adding BEV continued until disease progression (PD). The open-label randomised phase III IMELDA trial tested whether adding CAP to maintenance BEV continued until PD after initial BEV–DOC improves PFS.

Methods

Patients (pts) with HER2-negative measurable mBC, ECOG PS <2 and no prior chemotherapy for mBC were eligible. After 3–6 cycles of BEV–DOC, pts without PD were randomised to BEV alone or BEV-CAP (BEV 15 mg/kg q3w; CAP 1000 mg/m2 bid d1-14 q3w) until PD. Stratification factors were ER status, visceral metastases, response status and LDH concentration. The primary endpoint was PFS (from randomisation); secondary endpoints included RR, overall survival (OS) from randomisation, safety and quality of life. The sample size was calculated based on a PFS hazard ratio (HR) of 0.70 (median PFS 5.8→8.3 months). 360 enrolled pts were required for 290 randomised pts; 244 PFS events would provide 80% power at 5% 2-sided alpha.

Results

Between Jun 2009 and Mar 2011 (when enrolment was prematurely terminated) 284 pts were enrolled and treated; 185 (65%) were randomised.

BEV(N = 94) BEV–CAP(N = 91)
Median age, years (range) 54 (24–77) 49 (24–80)
Triple-negative mBC, n (%) 21 (22) 25 (27)
Visceral metastases, n (%)a 65 (69) 62 (68)
≥3 metastatic organs, n (%) 54 (57) 43 (47)
Median duration of follow-up, months (range)b 30.4 (1.3–43.3) 31.6 (0.8–41.6)
PFSb
Events, n (%) 83 (88) 69 (76)
HRc (95% CI) 0.38 (0.27–0.55)Log-rank p < 0.001c
Median PFS, months 4.3 11.9
OSb
Events, n (%) 53 (56) 33 (36)
HRc (95% CI) 0.43 (0.26–0.69)Log-rank p < 0.001c
Median OS, months 23.7 39.0
1-year OS rate, % (95% CI) 72 (61–80) 90 (82–95)
Grade ≥3 AEsb, n (%)
All 28 (30) 47 (52)
Hand-foot syndrome 0 30 (33)
Hypertension 3 (3) 8 (9)
Proteinuria 4 (4) 4 (4)
Gastroenteritis 3 (3) 0

aAt randomisation. bFrom randomisation. cStratified.

Conclusions

Adding CAP to maintenance BEV provided statistically significant and clinically meaningful improvements in PFS (HR 0.38, p < 0.001; median 11.9 vs 4.3 months) and OS (HR 0.43, p < 0.001; median 39.0 vs 23.7 months) at study closure, despite the smaller than planned sample size because of early termination of accrual, with a manageable increase in AEs mainly due to hand-foot syndrome.