NEW YORK (Reuters Health) Jun 22 - Imatinib mesylate offers hope for patients with metastatic melanoma harboring c-Kit mutations, Chinese researchers report.
"Before this JCO paper we published, there were three investigator initiated trials which used imatinib for unselected melanoma patients," Dr. Jun Guo from Peking University Cancer Hospital and Institute, Beijing, told Reuters Health by email.
In those trials there was only one objective response noted, Dr Jun Guo continued, and this was a patient with acral melanoma who had a c-Kit mutation. In the new phase II trial by Dr. Guo and colleagues, in which all patients harbored c-Kit mutations, there was a 54% disease control rate with imatinib, demonstrating the importance of patient selection.
Dr. Guo and colleagues evaluated progression-free survival, overall response rates, and overall survival in a phase II trial of imatinib in 43 patients with metastatic melanoma harboring c-Kit mutations and/or amplification of c-Kit gene copy number.
The 6-month progression-free survival rate was 36.6%, and the median progression-free survival was 3.5 months. Median progression-free survival was longer (albeit insignificantly) in patients harboring exon 11 or 13 mutations than in those harboring other aberrations but similar in patients with single and multiple aberrations.
Ten patients (23.3%) achieved partial responses, 13 patients (30.2%) had stable disease, and 20 patients (46.5%) had progressive disease, according to a June 20th online paper in the Journal of Clinical Oncology.
Over half the patients (53.5%) had early disease control (partial response plus stable disease), and 18 patients (41.9%) showed regression of tumor mass.
These results are "promising compared with largely ineffective therapies evaluated in patients without a definable predictive biomarker," the researchers note.
The one-year overall survival rate was 51.0%, and the median overall survival was 14.0 months. Overall survival was 15 months in patients who achieved a partial response or stable disease, compared to nine months in patients with disease progression (P=0.036).
Adverse events were generally of mild to moderate severity and easily managed by dose reduction, dose interruption, or supportive medical treatment, although toxicity was generally intolerable in the 15 patients who were allowed to escalate their daily imatinib dose from 400 to 800 mg.
"For these patients, most of them with stage IV disease and failed with chemotherapy, there are no standard treatments," Dr. Guo said.
"As we can imagine in the future, maybe we can distinguish melanoma patients into several groups," Dr. Guo said. For instance, patients with the Bref mutation could use PLX4032, and patients with c-Kit can use imatinib.
The study was supported by a grant from Novartis Oncology in China. One of the 21 authors received research funding from Novartis.
"Before this JCO paper we published, there were three investigator initiated trials which used imatinib for unselected melanoma patients," Dr. Jun Guo from Peking University Cancer Hospital and Institute, Beijing, told Reuters Health by email.
In those trials there was only one objective response noted, Dr Jun Guo continued, and this was a patient with acral melanoma who had a c-Kit mutation. In the new phase II trial by Dr. Guo and colleagues, in which all patients harbored c-Kit mutations, there was a 54% disease control rate with imatinib, demonstrating the importance of patient selection.
Dr. Guo and colleagues evaluated progression-free survival, overall response rates, and overall survival in a phase II trial of imatinib in 43 patients with metastatic melanoma harboring c-Kit mutations and/or amplification of c-Kit gene copy number.
The 6-month progression-free survival rate was 36.6%, and the median progression-free survival was 3.5 months. Median progression-free survival was longer (albeit insignificantly) in patients harboring exon 11 or 13 mutations than in those harboring other aberrations but similar in patients with single and multiple aberrations.
Ten patients (23.3%) achieved partial responses, 13 patients (30.2%) had stable disease, and 20 patients (46.5%) had progressive disease, according to a June 20th online paper in the Journal of Clinical Oncology.
Over half the patients (53.5%) had early disease control (partial response plus stable disease), and 18 patients (41.9%) showed regression of tumor mass.
These results are "promising compared with largely ineffective therapies evaluated in patients without a definable predictive biomarker," the researchers note.
The one-year overall survival rate was 51.0%, and the median overall survival was 14.0 months. Overall survival was 15 months in patients who achieved a partial response or stable disease, compared to nine months in patients with disease progression (P=0.036).
Adverse events were generally of mild to moderate severity and easily managed by dose reduction, dose interruption, or supportive medical treatment, although toxicity was generally intolerable in the 15 patients who were allowed to escalate their daily imatinib dose from 400 to 800 mg.
"For these patients, most of them with stage IV disease and failed with chemotherapy, there are no standard treatments," Dr. Guo said.
"As we can imagine in the future, maybe we can distinguish melanoma patients into several groups," Dr. Guo said. For instance, patients with the Bref mutation could use PLX4032, and patients with c-Kit can use imatinib.
The study was supported by a grant from Novartis Oncology in China. One of the 21 authors received research funding from Novartis.
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