Dataset Information

Melanoma patients in a phase I clinic: molecular aberrations, targeted therapy and outcomes.

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.

SUBMITTER: Henary H

PROVIDER: S-EPMC4081655 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Publications

Melanoma patients in a phase I clinic: molecular aberrations, targeted therapy and outcomes.

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

Annals of oncology : official journal of the European Society for Medical Oncology 20130410 8

<h4>Background</h4>The purpose of the study was to assess the outcome of patients with advanced melanoma treated with matched molecularly targeted therapy.<h4>Patients and methods</h4>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.<h4>Results</h4>Of 160 patien ...[more]

PMID: 23576709

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Dataset Information

Melanoma patients in a phase I clinic: molecular aberrations, targeted therapy and outcomes.

Background

Patients and methods

Results

Conclusions

Publications

Melanoma patients in a phase I clinic: molecular aberrations, targeted therapy and outcomes.

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