LBA26 - Weekly paclitaxel (PAC), pegylated liposomal doxorubicin (PLD) or topotecan (TOP) ± bevacizumab (BEV) in platinum (PT)-resistant recurrent ovarian...

Date 30 September 2012
Event ESMO Congress 2012
Session Gynecological cancer
Topics Anticancer agents
Ovarian Cancer
Therapy
Biological Therapy
Presenter Andrés Poveda
Authors A.M. Poveda1, F. Selle2, F. Hilpert3, A. Reuss4, A. Pasic5, A. Savarese6, I.B. Vergote7, P. Witteveen8, A. Bamias9, D. Bollag10, E. Pujade-Lauraine11
  • 1Area Clinica De Oncologia Ginecologica, GEICO and Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 2Medical Oncology, GINECO and Hôpital Tenon, 75020 - Paris/FR
  • 3Dept. Of Gynecology & Obstetrics, AGO and University Hospital Schleswig, 24105 - Kiel/DE
  • 4Biometrics, AGO and Klinische Studien Philipps-Universität Marburg, D-35043 - Marburg/DE
  • 5Medical Oncology Dept., NSGO and Institute of Oncology/Clinical Centre of Sarajevo University, BA-71000 - Sarajevo/BA
  • 6Division Of Medical Oncology A, MITO and National Cancer Institute "Regina Elena", 00144 - Rome/IT
  • 7Obstetrics & Gynaecology, BGOG and University Hospital Leuven, BE-3000 - Leuven/BE
  • 8Dept Of Medical Oncology, DGOG and University Medical Center Utrecht, 3508 GA - Utrecht/NL
  • 9Clinical Therapeutics, HECOG and University of Athens Medical School, GR-115 28 - Athens/GR
  • 10Pbmo, F. Hoffmann- La Roche AG, CH-4070 - Basel/CH
  • 11GINECO and Université Paris Descartes, AP-HP, Hôpitaux Universitaires Paris Centre, 75004 - Paris/FR

 

Abstract

BACKGROUND: AURELIA is the first trial to compare BEV + CT vs CT in PT-resistant recurrent OC. The hazard ratio (HR) for progression-free survival (PFS) by RECIST (primary endpoint) in the overall population was 0.48 (95% CI 0.38–0.60; p<0.001). We report exploratory analyses according to selected CT.
Methods: Eligible patients (pts) had OC that had progressed <6 mo after =4 cycles of PT-based therapy. Pts with refractory OC, history of bowel obstruction or >2 prior anticancer regimens were ineligible. Investigators chose single-agent CT (PAC 80 mg/m2 d1, 8, 15 & 22 q4w; PLD 40 mg/m2 d1 q4w; or TOP 4 mg/m2 d1, 8 & 15 q4w or 1.25 mg/m2 d1–5 q3w) for each pt before randomisation to CT either alone or with BEV (10 mg/kg q2w or 15 mg/kg q3w depending on CT) until progression, unacceptable toxicity or withdrawal of consent.

Results: Between Oct 2009 and Apr 2011, 361 pts were randomised. Baseline characteristics, CT exposure and efficacy are summarised below.

PAC (N=115)

PLD (N=126)

TOP (N=120)

CT (N=55)

BEV + CT (N=60)

CT (N=64)

BEV + CT (N=62)

CT (N=63)

BEV + CT (N=57)

Median age, y

60

60

62

63.5

61

60

FIGO stage III/IV, %

87

90

81

90

89

96

PT-free interval <3 mo, %

27

27

20

27

25

26

Median no. of CT cycles (range)

4
(1?15)

6
(1?13)

3
(1?17)

4
(1?11)

3
(1?11)

6
(1?14)

PFS

Events, %

89

62

95

87

89

77

Median, mo

3.9

10.4

3.5

5.4

2.1

5.8

HR (95% CI)a

0.46
(0.30–0.71)

0.57
(0.39–0.83)

0.32
(0.21–0.49)

ORR, %

28.8

51.7

7.9

18.3

3.3

22.8

Difference (95% CI)

22.9
(3.9–41.8)

10.4
(–2.4 to 23.2)

19.5
(6.7–32.3)

aNot stratified

ORR = overall response rate (RECIST and/or CA-125)

BEV + CT was associated with a higher incidence of grade =2 peripheral sensory neuropathy in the PAC cohort (35% vs 22% with CT), grade =2 hand-foot syndrome in the PLD cohort (27% vs 14%) and grade =2 hypertension and proteinuria in the PAC and PLD but not the TOP cohort. Grade =3 abdominal pain, vomiting and fatigue were more common with CT than BEV + CT in all cohorts.

Conclusion: In PT-resistant OC, the improvement in PFS and ORR gained by adding BEV to single-agent CT was observed across all CT cohorts. Increased CT exposure associated with prolonged PFS accounts for some increase in cumulative CT toxicity.