ABSTRACT
Clinical trials of targeted therapy (TT) and immunotherapy (IT) for highly aggressive advanced melanoma have shown marked improvements in response and survival rates. However, real-world data on treatment patterns and clinical outcomes for patients with advanced BRAF V600 mutant melanoma are ultimately scarce. The study was designed as an observational retrospective chart review study, which included 382 patients with advanced BRAF V600 mutant melanoma, who received TT in a real-world setting and were not involved in clinical trials. The data were collected from twelve medical centers in Russia. The objective response rates (ORRs) to combined BRAFi plus MEKi and to BRAFi mono-therapy were 57.4% and 39.8%, respectively. The median progression-free survival (PFS) and median overall survival (OS) were 9.2 months and 22.6 months, respectively, for the combined first-line therapy; 9.4 months and 16.1 months, respectively, for the combined second-line therapy; and 7.4 months and 17.1 months, respectively, for the combined third- or higher-line therapy. Analysis of treatment patterns demonstrated the effectiveness of the combined TT with BRAF plus MEK inhibitors in patients with brain metastases, rare types of BRAF mutations, and across lines of therapy, as well as a well-tolerated and manageable safety profile.
ABSTRACT
Vemurafenib, a specific inhibitor of mutated BRAF kinase, may activate wild-type BRAF and therefore induce squamous cell skin carcinomas in patients treated for melanoma. All vemurafenib clinical trials excluded patients with multiple primary malignant tumors; therefore, the action of this drug on concurrent BRAF wild-type malignancies remains insufficiently studied. We observed a patient, who was administered vemurafenib for BRAF mutation-containing melanoma, but experienced immediate relapse of previously controlled breast cancer disease. Interestingly, breast cancer lesions underwent regression soon after vemurafenib discontinuation. Therefore, caution must be taken while considering vemurafenib treatment for patients with multiple tumors.
Subject(s)
Antineoplastic Agents/adverse effects , Breast Neoplasms/pathology , Carcinoma, Squamous Cell/chemically induced , Indoles/adverse effects , Neoplasm Recurrence, Local/chemically induced , Sulfonamides/adverse effects , Breast Neoplasms/drug therapy , Disease Progression , Female , Humans , Indoles/therapeutic use , Melanoma/drug therapy , Melanoma/pathology , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Proto-Oncogene Proteins B-raf/metabolism , Sulfonamides/therapeutic use , VemurafenibABSTRACT
PURPOSE: To evaluate the efficacy of adding lapatinib to capecitabine and oxaliplatin (CapeOx) in patients with previously untreated human epidermal growth factor receptor 2 (HER2) -amplified advanced gastroesophageal adenocarcinoma. PATIENTS AND METHODS: Patients with HER2-positive advanced gastroesophageal adenocarcinoma were randomly assigned at a one-to-one ratio to CapeOx plus lapatinib 1,250 mg or placebo daily. Primary end point was overall survival (OS) in patients with centrally confirmed HER2 amplification in the primary efficacy population. RESULTS: A total of 545 patients were randomly assigned, and 487 patients comprised the primary efficacy population. Median OS in the lapatinib and placebo arms was 12.2 (95% CI, 10.6 to 14.2) and 10.5 months (95% CI, 9.0 to 11.3), respectively, which was not significantly different (hazard ratio, 0.91; 95% CI, 0.73 to 1.12). Median progression-free survival in the lapatinib and placebo arms was 6.0 (95% CI, 5.6 to 7.0) and 5.4 months (95% CI, 4.4 to 5.7), respectively (hazard ratio, 0.82; 95% CI, 0.68 to 1.00; P = .0381). Response rate was significantly higher in the lapatinib arm: 53% (95% CI, 46.4 to 58.8) compared with 39% (95% CI, 32.9 to 45.3) in the placebo arm (P = .0031). Preplanned exploratory subgroup analyses showed OS in the lapatinib arm was prolonged in Asian and younger patients. No correlation was observed between HER2 immunohistochemistry status and survival. There were increased toxicities in the lapatinib arm, particularly diarrhea. CONCLUSION: Addition of lapatinib to CapeOx did not increase OS in patients with HER2-amplified gastroesophageal adenocarcinoma. There were clear differences in the effect of lapatinib depending on region and age. Future studies could examine this correlation.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/genetics , Esophageal Neoplasms/drug therapy , Esophagogastric Junction/drug effects , Receptor, ErbB-2/genetics , Stomach Neoplasms/drug therapy , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Capecitabine/administration & dosage , Double-Blind Method , Esophageal Neoplasms/genetics , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophagogastric Junction/pathology , Female , Follow-Up Studies , Gene Amplification , Humans , Lapatinib , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Polymerase Chain Reaction , Prognosis , Quinazolines/administration & dosage , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival Rate , Young AdultABSTRACT
We report a patient with a metastatic relapse of clear cell sarcoma, whose tumor harbored BRAF V600E mutation. Standard chemotherapy with doxorubicin and ifosfamide failed to slow the disease progression. Subsequent administration of vemurafenib (960 mg twice a day) resulted in complete tumor response after 8 weeks of treatment. Literature data on the use of vemurafenib and dabrafenib in non-melanoma BRAF-mutated tumors are reviewed.
