Panitumumab, Gemcitabine, and Carboplatin as Treatment for Women With Metastatic Triple-Negative Breast Cancer: A Sarah Cannon Research Institute Phase II Trial.

BACKGROUND: Triple-negative breast cancer (TNBC) is a subtype with poor prognosis, and treatment options are limited to chemotherapy. Because the epidermal growth factor receptor (EGFR) is overexpressed in up to 70% of these tumors, this phase II trial was designed to evaluate the efficacy and safety of panitumumab in combination with gemcitabine and carboplatin as first- or second-line treatment for metastatic TNBC. PATIENTS AND METHODS: Adult women with metastatic TNBC with a maximum of 1 previous chemotherapy regimen were eligible. Patients received gemcitabine intravenous (I.V.) 1500 mg/m2, carboplatin area under the concentration-time curve = 2.5 I.V., and panitumumab 6 mg/kg I.V. every 2 weeks. Treatment continued until disease progression or unacceptable toxicity, with disease evaluations every 6 weeks. The primary end point was progression-free survival (PFS). Archival tissue was collected for correlative analysis, to include phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, p53, phosphatase and tensin homolog, EGFR, and status. RESULTS: Between May 2010 and August 2012, 71 women (median age, 54 years; 14% de novo stage IV) were treated. At a median follow-up of 11 months, the median PFS was 4.4 months (95% confidence interval, 3.2-5.5 months). The objective response rate was 42% (complete response, 1; partial response, 29). Treatment-related toxicity included: rash, 50 patients (70%), fatigue, 37 patients (52%), neutropenia, 32 patients (45%; 2 episodes of febrile neutropenia), and thrombocytopenia, 32 patients (45%). CONCLUSION: Although the addition of panitumumab was feasible, the results of this trial do not support combination of panitumumab with gemcitabine and carboplatin in the treatment of patients with TNBC.

Concurrent radiotherapy and temozolomide followed by temozolomide and sorafenib in the first-line treatment of patients with glioblastoma multiforme.

BACKGROUND: The current study was conducted to evaluate the efficacy of sorafenib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, when added to standard radiotherapy and temozolomide in the first-line treatment of patients with glioblastoma multiforme. METHODS: After initial surgical resection or biopsy, patients with newly diagnosed glioblastoma multiforme received concurrent radiotherapy (2.0 grays [Gy]/day; total dose, 60 Gy) and temozolomide (at a dose of 75 mg/m2 orally daily), followed by 6 months of maintenance therapy with temozolomide (at a dose of 150 mg/m2 orally on Days 1-5 every 28 days) and sorafenib (at a dose of 400 mg orally twice daily). Patients were re-evaluated every 2 months; the primary endpoint of the trial was progression-free survival (PFS). RESULTS: A total of 47 patients were treated; 34 had undergone previous debulking surgery. Nineteen patients withdrew from treatment before the initiation of maintenance therapy with temozolomide and sorafenib (12 because of early tumor progression). Twenty-eight patients (60% of enrolled patients) received 4 months of maintenance therapy with temozolomide and sorafenib, and 9 patients (19%) completed the planned 6 months of maintenance therapy. The median PFS for the entire group was 6 months (95% confidence interval [95% CI], 3.7-7 months), with a 1-year PFS rate of 16%. The median overall survival was 12 months (95%CI, 7.2-16 months). Maintenance therapy with temozolomide and sorafenib was found to be well tolerated by most patients, with no grade 3/4 toxicity (according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) reported to occur in >10% of patients. CONCLUSIONS: The addition of sorafenib did not appear to improve the efficacy of treatment when compared with the results expected with standard therapy. A substantial percentage of patients (40%) did not receive any maintenance sorafenib, most often because of early disease progression. The administration of angiogenesis inhibitors concurrently with radiotherapy and temozolomide may optimize the opportunity to improve therapy.