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 Anti-Cancer Agents & Biologic Therapy
Ovarian Cancer
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.