Faculty Collaboration Database

Melanoma patients in a phase I clinic: molecular aberrations, targeted therapy and outcomes. Ann Oncol 2013 Aug;24(8):2158-65

Date

04/12/2013

Pubmed ID

23576709

Pubmed Central ID

PMC4081655

DOI

10.1093/annonc/mdt115

Scopus ID

2-s2.0-84881221698 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

BACKGROUND: The purpose of the study was to assess the outcome of patients with advanced melanoma treated with matched molecularly targeted therapy.

PATIENTS AND METHODS: We reviewed 160 consecutive patients with metastatic melanoma treated in the phase I program (N = 35 protocols). Treatment was considered to be 'matched' (N = 84) if at least one drug in the regimen was known to inhibit the functional activity of at least one of the patient's mutations.

RESULTS: Of 160 patients, 134 (83.7%) had adequate tissue for molecular analysis; 69% (110 of 160) had ≥1 mutation: 61.2% (82 of 134), BRAF; 20.7% (23 of 111), NRAS; 2.6% (2 of 77), KIT; 2.3% (1 of 44), KRAS; 20% (1 of 5), GNAQ; 11.1% (1 of 9), P53 and 2.6% (1 of 39), coexisting mutations in BRAF and PIK3CA. Eighty-four patients (52.4%) were treated with matched-targeted agents, most of whom had BRAF mutations (N = 74). Twenty-six percent of patients (41 of 160) achieved a complete or partial remission (CR/PR) [40% (34 of 84)) on a matched phase I protocol versus 9.2% (7 of 76) for those on a non-matched study (P ≤ 0.0001)]. The median progression-free survival (PFS) (95% CI) was longer for patients treated on a matched phase I trial than on their prior first standard treatment [5.27 (4.10, 6.44) versus 3.10 (1.92, 4.28) months, P = 0.023], but not on non-matched phase I treatment. Multivariable analysis showed that matched therapy was an independent predictor of higher CR/PR rates, prolonged PFS and survival.

CONCLUSIONS: For melanoma patients, especially those with BRAF mutations, administering molecularly matched agents can be associated with better outcomes, including longer PFS compared with their first-line systemic therapy.

Author List

Henary H, Hong DS, Falchook GS, Tsimberidou A, George GC, Wen S, Wheler J, Fu S, Naing A, Piha-Paul S, Janku F, Kim KB, Hwu P, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Class I Phosphatidylinositol 3-Kinases
Disease-Free Survival
Female
GTP Phosphohydrolases
GTP-Binding Protein alpha Subunits
GTP-Binding Protein alpha Subunits, Gq-G11
Humans
Male
Melanoma
Membrane Proteins
Middle Aged
Molecular Targeted Therapy
Phosphatidylinositol 3-Kinases
Precision Medicine
Proto-Oncogene Proteins
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins c-kit
Proto-Oncogene Proteins p21(ras)
Survival
Treatment Outcome
Tumor Suppressor Protein p53
Young Adult
ras Proteins