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Annals of Oncology
Methods: A cost-effectiveness analysis compared three treatments: 6 cycles of
paclitaxel and carboplatin (PC), 6 cycles of PC plus bevacizumab followed by 12
cycles of maintenance bevacizumab (PCB), and 6 cycles of dose-dense weekly
paclitaxel and carboplatin (ddPC). Data were taken from reported results of ICON7
(PC and PCB) and JGOG3016 (ddPC). Actual and estimated costs of treatment plus
costs of complications were established for each regimen. Progression-free survival and
rates of complications were estimated based on the results of clinical trials. Incremental
cost-effective ratios (ICER) per progression-free life-year saved (PFLYS) were estimated.
Results: The ICER for ddPC was $5,000 per PFLYS compared to PC. For PCB
compared to PC, the ICER was $285,000 per PFLYS. When compared
simultaneously, PCB was more costly and less effective than ddPC.
Conclusions: In this model, dose-dense weekly paclitaxel and carboplatin is more
cost effective than PCB for the treatment of advanced ovarian cancer.
Disclosure: All authors have declared no conflicts of interest.
974PD A PHASE 1 STUDY OF THE ANTI-ERBB3 ANTIBODY MM-121
IN COMBINATION WITH WEEKLY PACLITAXEL IN PATIENTS
WITH ADVANCED GYNECOLOGICAL AND BREAST CANCERS
J. Liu 1 , R. Patel 2 ,G.Kato 3 , U. Matulonis 1 , V. Moyo 4 , K. Riahi 4 , J. Pearlberg 5 ,
A. Czibere 4 , S. Isakoff 6
1 Gynecology, Dana Farber Cancer Institute, Boston, MA, UNITED STATES OF
AMERICA, 2 Research Department, Comprehensive Blood and Cancer Center,
Bakersfield, CA, UNITED STATES OF AMERICA, 3 Research, Pinnacle Oncology
Hematology, Scottsdale, AZ, UNITED STATES OF AMERICA, 4 Clinical
Development, Merrimack Pharmaceuticals, Cambridge, MA, UNITED STATES
OF AMERICA, 5 Sanofi Oncology, Sanofi, Cambridge, MA, UNITED STATES OF
AMERICA, 6 Department of Hematology and Medical Oncology, Massachusetts
General Hospital, Boston, MA, UNITED STATES OF AMERICA
Background: MM-121 is a fully human monoclonal antibody targeting the
epidermal growth factor receptor family member ErbB3. ErbB3 has been widely
implicated in driving cancer growth and in the development of resistance to
conventional chemotherapies and targeted agents across multiple malignancies.
Single agent weekly paclitaxel is a standard regimen for patients with advanced
gynecological and metastatic breast cancers. Here we present results from an
ongoing Phase 1 study evaluating the combination of MM-121 and weekly
paclitaxel.
Methods: A total of 24 patients with either platinum resistant ovarian cancer,
metastatic endometrial cancer, or HER2 negative metastatic breast cancer, were
treated in a dose escalation (12 pts) or expansion cohort (12 pts). Patients were
treated until disease progression or intolerable toxicity. Response was assessed every
eight (8) weeks according to RECIST 1.1. In the dose-expansion cohorts, pre- and
post-treatment fresh tumor biopsies were obtained from 12 patients to assess ErbB3
signaling status and its potential as a predictive marker for MM-121 response.
Results: To date, 24 patients have been treated with a median follow up of 5.5
months (range 0.8 – 13.1). The median age was 58 years (range 38 – 72), and
patients had received a median of four (range 1 – 11) prior lines of therapy.
Common (>20%) adverse events of any grade included fatigue (62%), peripheral
neuropathy (58%), diarrhea (46%), neutropenia (46%) and rash (38%). Grade 3/4
toxicities included fatigue (17%), peripheral neuropathy (8%), diarrhea (12%),
neutropenia (16%), anemia (4%), abdominal pain (8%), and hypokalemia (4%). 17
(71%) patients were evaluable for response and the overall clinical benefit rate, defined
as PR or SD lasting for >4 months, was 71%. 47% achieved a PR and 35% a confirmed
PR with a median duration of response of 4.6 months (range1.7 – 9.6) and 24% had
SD >4 months with a median duration of SD of 5.6 months (range 4.2-12.6). 17%
patients had PD at first assessment and 38% remain on study with a median on-study
time of 10.2 months (range 1.4 – 13.1). Translational analyses exploiting tissue analysis
in combination with in silico modeling are ongoing.
Conclusion: The combination of MM121 and paclitaxel showed activity in metastatic
ovarian and breast cancers.
Disclosure: J. Liu: Joyce Liu is an investigator participating in the corporatesponsored
study which is the subject of the abstract. R. Patel: Ravi Patel is an
investigator participating in the corporate-sponsored study which is the subject of
the abstract. G. Kato: Giraldo Kato is an investigator participating in the
corporate-sponsored study which is the subject of the abstract. U. Matulonis: Ursula
Matulonis is an investigator participating in the corporate-sponsored study which is the
subject of the abstract. V. Moyo: Victor Moyo is employed by and owns stock in the
corporate sponsor of this reserach. K. Riahi: Kaveh Riahi is employed by and owns stock
in the corporate sponsor of this research. J. Pearlberg: Joseph Pearlberg is employed by
and owns stock in a corporate sponsor of this research. A. Czibere: Akos Czibere is
employed by and owns stock in the corporate sponsor of this research. S. Isakoff: Steven
Isakoff is an investigator participating in the corporate-sponsored study which is the
subject of the abstract. He has also served as a consulant to Merrimack Pharmaceuticals.
975PD A PHASE 1B STUDY OF AMG 386 PLUS PACLITAXEL AND
CARBOPLATIN IN OVARIAN CANCER PATIENTS
UNDERGOING PRIMARY OR INTERVAL DEBULKING
SURGERY
I.B. Vergote 1 , A. Oaknin Benzaquen 2 , J. Baurain 3 , S. Ananda 4 , S. Wong 5 ,
X. Yang 6 ,B.Wu 7 , Z. Zhong 8 , M. Puhlmann 9 , A. Casado 10
1 Gynecologic Oncology, University Hospital Leuven, Leuven Cancer Institute,
Leuven, BELGIUM, 2 Medical Oncology, Vall d’Habron University Hospital,
Barcelona, SPAIN, 3 Service d’Oncologie Medicale, Universite Catholique de
Louvain, Bruxelles, BELGIUM, 4 Oncology Unit, Royal Women’s Hospital,
Parkville, VIC, AUSTRALIA, 5 Medical Oncology, Western Hospital, Footscray,
VIC, AUSTRALIA, 6 Department of Biostatistics, Amgen Inc., Thousand Oaks,
CA, UNITED STATES OF AMERICA, 7 Department of Pharmacokinetics and Drug
Metabolism, Amgen Inc., Thousand Oaks, CA, UNITED STATES OF AMERICA,
8 Department of Clinical Immunology and Biological Sample Management,
Amgen Inc., Thousand Oaks, CA, UNITED STATES OF AMERICA, 9 Department
of Clinical Development, Amgen Inc., Thousand Oaks, CA, UNITED STATES OF
AMERICA, 10 Medical Oncology, Hospital Clínico San Carlos, Madrid, SPAIN
Background: AMG 386, an investigational peptibody, blocks the interaction of
angiopoietin-1 and -2 with the Tie2 receptor, thereby inhibiting tumor angiogenesis.
We evaluated the tolerability of AMG 386 plus paclitaxel and carboplatin in ovarian
cancer patients who had primary or interval debulking surgery (PDS or IDS,
respectively).
Methods: Women (≥ 18 yrs, GOG ≤ 1) with high-risk stage I (grade 3 or aneuploid
grade 1 or 2) or II-IV ovarian cancer received 6 cycles of the combination AMG 386
(15 mg/kg IV QW) plus paclitaxel (175 mg/m 2 IV Q3W) and carboplatin (AUC 6 IV
Q3W) followed by AMG 386 maintenance monotherapy up to 18 months. Patients
had PDS; patients with disease stage IIIC or IV had the option of planned IDS.
AMG 386 dosing was withheld for > 4 weeks after PDS or before IDS. The primary
endpoint was the incidence of dose-limiting toxicities (DLTs), which determined
cohort expansion to n = 25; secondary endpoints included the patient incidence of
adverse events (AEs), the incidence of anti-AMG 386 antibody formation, and
pharmacokinetics (PK). The current report presents results from the study’s
combination therapy phase.
Results: At interim analysis, 27 patients (14 PDS, 13 IDS) were enrolled and
received ≥ 1 dose of AMG 386 plus paclitaxel and carboplatin. No patients
experienced DLTs. The patient incidence of AEs is summarized in the table below. 4
of 24 patients developed non-neutralizing binding antibodies; 1 of 26 patients had
pre-existing, non-neutralizing binding antibodies. Coadministration of AMG 386 did
not alter the PK of paclitaxel or carboplatin.
AMG 386 +
paclitaxel and carboplatin (n = 27)
Patient incidence of
AEs – n (%)
PDS (n = 14; 52%) IDS (n = 13; 48%)
Patients with any
adverse event
14 (100) 12 (92)
Worst grade ≥ 3 7 (50) 5 (38)
Worst grade ≥ 4 3 (21)* 2 (15)**
Worst grade 5 0 (0) 0 (0)
In ≥ 20% of patients Any Worst grade ≥ 3 Any Worst grade ≥ 3
who had PDS or
IDS
grade
grade
Localized edema 8 (57) 0 (0) 3 (23) 0 (0)
Diarrhea 7 (50) 0 (0) 5 (38) 0 (0)
Nausea 7 (50) 0 (0) 6 (46) 0 (0)
Fatigue 7 (50) 0 (0) 5 (38) 0 (0)
Thrombocytopenia 3 (21) 1 (7) 6 (46) 2 (15)
Decreased appetite 2 (14) 0 (0) 6 (46) 0 (0)
Asthenia 6 (43) 0 (0) 4 (31) 0 (0)
Neutropenia 5 (36) 4 (29) 3 (23) 2 (15)
Nasopharyngitis 5 (36) 0 (0) 0 (0) 0 (0)
Alopecia 5 (36) 0 (0) 0 (0) 0 (0)
Abdominal
distension
1 (7) 0 (0) 4 (31) 0 (0)
Abdominal pain 2 (14) 0 (0) 4 (31) 0 (0)
Constipation 4 (29) 0 (0) 4 (31) 0 (0)
Peripheral sensory
neuropathy
4 (29) 0 (0) 4 (31) 0 (0)
Hypokalemia 0 (0) 0 (0) 4 (31) 1 (8)
Peripheral
neuropathy
4 (29) 0 (0) 0 (0) 0 (0)
Continued
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds401 | ix321