Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study.
BACKGROUND
This phase II study evaluated the safety and activity of ipilimumab, a fully human mAb that blocks cytotoxic T-lymphocyte antigen-4, in patients with advanced melanoma.


METHODS
Patients with previously treated, unresectable stage III/stage IV melanoma received 10 mg/kg ipilimumab every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. The primary end point was best overall response rate (BORR) using modified World Health Organization (WHO) criteria. We also carried out an exploratory analysis of proposed immune-related response criteria (irRC).


RESULTS
BORR was 5.8% with a disease control rate (DCR) of 27% (N = 155). One- and 2-year survival rates (95% confidence interval) were 47.2% (39.5% to 55.1%) and 32.8% (25.4% to 40.5%), respectively, with a median overall survival of 10.2 months (7.6-16.3). Of 43 patients with disease progression by modified WHO criteria, 12 had disease control by irRC (8% of all treated patients), resulting in a total DCR of 35%. Adverse events (AEs) were largely immune related, occurring mainly in the skin and gastrointestinal tract, with 19% grade 3 and 3.2% grade 4. Immune-related AEs were manageable and generally reversible with corticosteroids.


CONCLUSIONS
Ipilimumab demonstrated clinical activity with encouraging long-term survival in a previously treated advanced melanoma population.
O'Day
S J
SJ
The Angeles Clinic and Research Institute, Santa Monica, CA, USA. Electronic address: SODay@theangelesclinic.org.
Maio
M
M
Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena.
Chiarion-Sileni
V
V
Department of Melanoma and Skin Cancer Unit, IOV-IRCCS, Padua, Italy.
Gajewski
T F
TF
Department of Pathology; Department of Medicine, University of Chicago, Chicago, IL, USA.
Pehamberger
H
H
Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Bondarenko
I N
IN
Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine.
Queirolo
P
P
Department of Medical Oncology A, National Institute for Cancer Research, Genova, Italy.
Lundgren
L
L
Department of Oncology, Lund University Hospital, Lund, Sweden.
Mikhailov
S
S
Stavropol Regional Clinical Oncology Center, Stavropol.
Roman
L
L
Leningrad Regional Oncology Center, St Petersburg, Russian Federation.
Verschraegen
C
C
University of New Mexico Cancer Center, Albuquerque, NM.
Humphrey
R
R
Bristol-Myers Squibb Company, Wallingford, CT, USA.
Ibrahim
R
R
Bristol-Myers Squibb Company, Wallingford, CT, USA.
de Pril
V
V
Bristol-Myers Squibb Company, Braine-l'Alleud, Belgium.
Hoos
A
A
Bristol-Myers Squibb Company, Wallingford, CT, USA.
Wolchok
J D
JD
Department of Medicine and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis
D000911:Antibodies, Monoclonal; D000074324:Ipilimumab