2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

ANTIANGIOGENICS AND PARP INHIBITORS IN OVARIAN CANCER
Trial
No. of
Patients Setting Trial Arms
GOG-0218 6
1873 First (CP � 6 � Pl � 5)
line 3 Pl � 17
ICON7 5
OCEANS 9
1528 First
line
0262 is a phase III trial of 3-weekly paclitaxel/carboplatin
compared with dose-dense weekly paclitaxel/3-weekly carboplatin
with optional addition of bevacizumab 15 mg/kg in
both arms.
Bevacizumab As Second-Line Treatment in
Ovarian Cancer
The OCEANS trial was a randomized, double-blinded,
placebo-controlled phase III trial of carboplatin AUC 4
on day 1 and gemcitabine 1000 mg/m 2 on days 1 and 8,
3-weekly with or without bevacizumab 15 mg/kg in patients
KEY POINTS
Table 1. Summarized Results of the Three Phase III trials of Bevacizumab in Ovarian Cancer
Bevacizumab
Dose
(mg/kg)
● Bevacizumab increases progression-free survival
(PFS) by 2 to 4 months when added to first- or
second-line chemotherapy and continued as maintenance
treatment in ovarian cancer.
● Bevacizumab 7.5 mg/kg in a subgroup of patients
with stage III suboptimally debulked and stage IV
disease improved survival by 8 months.
● Bevacizumab should be considered for patients who
are at high risk of having a short PFS because the
bevacizumab might delay symptoms and these patients
with platinum-resistant disease are unlikely
to have an opportunity to receive bevacizumab as
part of second-line treatment.
● Poly (ADP-ribose) polymerase (PARP) inhibitors have
shown response rates of up to 69% in early-phase
trials of a patient population with recurrent ovarian
cancer and enriched for patients with BRCA1/2
mutations.
Overall
Response Rate Progression Death
% 95% CI p HR 95% CI p HR 95% CI p
15 Not
reported
CP � 6 � BEV � 5 0.908* 0.795 to
1.040
(CP � 6 �BEV�5)
3 BEV � 17
484 Second (CG�Pl) � 6
line, 3 Pl � 21
platinum or PD
sensitive (CG�BEV) � 6
3 BEV � 21
or PD
CP � 6 7.5 48 0.87*† 0.77 to
0.99
(CP�BEV) � 6
67 11% to � .001 0.73*‡ 0.60 to
3 BEV � 12
(difference
� 19)
28%
0.93
15 57 51% to
64%
78 73% to
84%
with platinum-sensitive recurrent disease. Preliminary data
were presented at ASCO in 2011. 9 PFS was significantly
increased in the bevacizumab arm (12.4 vs. 8.4 months).
The AURELIA (NCT00976911) trial, which reports this
year, evaluates the impact of adding bevacizumab (10 mg/kg
every 2 weeks or 15 mg/kg every 3 weeks) to either dosedense
paclitaxel 80 mg/m 2 weekly or topotecan 4 mg/m 2 on
days 1, 8, and 15 of each 4-week cycle (or 1.25 mg/m 2 on day
1 through 5 of each 3-week cycle) or liposomal doxorubicin
40 mg/m 2 every 4 weeks. Only patients with platinumresistant
ovarian cancer are eligible.
The GOG-0213 (NCT0056585) trial is investigating the
role of adding bevacizumab 15 mg/kg to six cycles of carboplatin
AUC 5 and paclitaxel 175 mg/m 2 , followed by 3-weekly
bevacizumab until disease progression in platinum-sensitive
recurrent ovarian cancer. Patients are allowed to have
received prior bevacizumab, and this trial is also evaluating
the role of secondary cytoreductive surgery. 10
Antiangiogenic Small-Molecule Tyrosine
Kinase Inhibitors
Median Survival
(months)
Progression
Free Overall
10.3 39.3
.16* 1.036 0.827 to
1.297
.76 11.2 38.7
0.717* 0.625 to � .001* 0.915 0.727 to .45 14.1 39.7
0.824
1.152
0.48 0.39 to
0.61
Abbreviations: BEV, bevacizumab; C, carboplatin; G, gemcitabine; HR, hazard ratio; P, paclitaxel; Pl, placebo.
* HR for progression or death.
† All patients.
§ Restricted mean values.
‡ High-risk patients.
.04 0.85 0.69 to
1.04
� .001 0.64 0.48 to
0.85
.11 22.4§
24.1§
.002 14.5§
18.1§
Not yet
reached
28.8
36.6
� .0001 0.751 0.537 to .094 8.4 Not yet
1.052
reached
� .0001 12.4
Randomized trials of three antiangiogenic tyrosine kinase
inhibitors in patients with ovarian cancer should present
results within the next 2 years. 2 The AGO-Ovar 12/LUME-
Ovar 1 trial is evaluating intedanib in combination with
3-weekly paclitaxel and carboplatin, followed by intedanib
maintenance up to a total of 120 weeks in patients with
stage IIB to IV epithelial ovarian, fallopian tube, or primary
peritoneal cancer after prior tumor-debulking surgery. Pazopanib
is being studied as maintenance therapy for up to 2
years, in a randomized, two-arm, placebo controlled, phase
III study in women with ovarian, fallopian tube, or primary
peritoneal cancer that has not progressed after completing
first-line chemotherapy for advanced ovarian cancer. The
ICON6 trial is investigating carboplatin and paclitaxel che-
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