Efficacy and safety of nilotinib in patients with KIT-mutated metastatic or inoperable melanoma: final results from the global, single-arm, phase II TEAM trial.
BACKGROUND
The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT-mutated advanced melanoma without prior KIT inhibitor treatment.


METHODS
Forty-two patients with KIT-mutated advanced melanoma were enrolled and treated with nilotinib 400 mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients; the design was amended to a single-arm trial due to an observed low number of KIT-mutated melanomas. Thirteen patients were randomized to DTIC before the protocol amendment removing this study arm. The primary endpoint was objective response rate (ORR), determined according to Response Evaluation Criteria In Solid Tumors.


RESULTS
ORR was 26.2% (n = 11/42; 95% CI, 13.9%-42.0%), sufficient to reject the null hypothesis (ORR ≤10%). All observed responses were partial responses (PRs; median response duration, 7.1 months). Twenty patients (47.6%) had stable disease and 10 (23.8%) had progressive disease; 1 (2.4%) response was unknown. Ten of the 11 responding patients had exon 11 mutations, four with an L576P mutation. The median progression-free survival and overall survival were 4.2 and 18.0 months, respectively. Three of the 13 patients on DTIC achieved a PR, and another patient had a PR following switch to nilotinib.


CONCLUSIONS
Nilotinib activity in patients with advanced KIT-mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential activity, although the low patient number limits interpretation. Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations.


BACKGROUND
ClinicalTrials.gov, NCT01028222.
Department of Renal Cancer & Melanona, Peking University Cancer Hospital & Institute, Beijing, China.
J
J
Guo
Division of Hematology/Oncology, Columbia University Medical Center, New York, USA.
R D
RD
Carvajal
Skin Cancer Center, University Hospital of Zurich, Zurich, Switzerland.
R
R
Dummer
Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany.
A
A
Hauschild
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco.
A
A
Daud
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco.
B C
BC
Bastian
Department of Hematology/Oncology, Mayo Clinic Cancer Center, Rochester, USA.
S N
SN
Markovic
Department of Medical Oncology, National Research Institute for Cancer, Genova, Italy.
P
P
Queirolo
Department of Medical Oncology, Hospital Clinic, Barcelona, Spain.
A
A
Arance
Department of Dermatology & Allergology, University Hospital Munich (LMU), Munich, Germany.
C
C
Berking
Department of Medical Oncology, Cancer Institute of São Paulo, São Paulo.
V
V
Camargo
Department of Clinical Oncology, National Institute of Cancer, Rio de Janeiro, Brazil.
D
D
Herchenhorn
Department of Medical Oncology, Sunnybrook Health Sciences Center, Toronto, Canada.
T M
TM
Petrella
Department of Dermatology, Essen University Hospital, Essen, Germany.
D
D
Schadendorf
Department of Oncology & Dermatology, Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Medicine, Lutherville, USA.
W
W
Sharfman
Melanoma and Muscle Cutaneous Sarcoma Division, European Institute of Oncology, Milano, Italy.
A
A
Testori
Oncology Business Unit, Novartis Pharmaceuticals Corporation, East Hanover, USA.
S
S
Novick
Oncology Business Unit, Novartis Pharma AG, Basel, Switzerland.
S
S
Hertle
Oncology Business Unit, Novartis Pharma AG, Basel, Switzerland.
C
C
Nourry
Oncology Business Unit, Novartis Pharmaceuticals Corporation, East Hanover, USA.
Q
Q
Chen
Melanoma Center, Dana-Farber Cancer Institute, Boston, USA.
F S
FS
Hodi
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000627:therapeutic use; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis
D000970:Antineoplastic Agents; D011743:Pyrimidines; D003606:Dacarbazine; D019009:Proto-Oncogene Proteins c-kit; C498826:nilotinib
KIT; dacarbazine; imatinib; melanoma; nilotinib; tyrosine kinase inhibitor