OncoPrescribe LLC published their first newsletter on metastatic lung cancer. The title of the article is “Improving Survival for Patients with Advanced Non−Small-Cell Lung Cancer”. This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of A. Webb Roberts Center for CME of Baylor Health Care System and Oncoprescribe, LLC. A. Webb Roberts Center for CME of Baylor Health Care System is accredited by the ACCME to provide continuing medical education for physicians.
Category: Hem/Onc Updates
OncoPrescribe for all Health Care Professionals
Oncoprescribe is a comprehensive Web-Based Resource for Oncologists, Nurses, Nurse Practitioners, Physician Assistants and Pharmacists. OncoPrescribe is regularly updated by our Oncology professionals who scour the published literature – and constantly attend conferences at which the latest research findings are presented.
With OncoPrescribe, you’ll probably see regimens available for specific diagnoses and stages that you didn’t even know about, and you’ll be able to prescribe that regimen with confidence because you’ll know there’s a corresponding reference, too.
So, what are you waiting for? Check it out. You will love it
Brentuximab vedotin (SGN-35) for Hodgkins Lymphoma and Systemic Anaplastic large cell Lymphoma
SUMMARY: Brentuximab vedotin (SGN-35) is an antibody-drug conjugate (ADC) that targets CD30, which is a protein expressed on cancer cells in patients with Hodgkin’s lymphoma (HL) as well as Anaplastic Large Cell Lymphoma (ALCL), an aggressive type of T-cell non-Hodgkin’s lymphoma. This ADC consists of an anti-CD30 monoclonal antibody linked to monomethyl auristatin E (MMAE), an antimicrotubule agent. Upon binding to the CD30 molecule on the cancer cells, MMAE is released into the cancer cell resulting in cell death. Taking advantage of this dual action, targeted mechanism of action of brentuximab vedotin , two phase II studies were conducted, one in patients with relapsed or refractory HL and the other in patients with relapsed or refractory systemic ALCL. In the HL pivotal trial, 102 relapsed or refractory Hodgkin lymphoma patients who had failed prior autologous stem cell transplant (ASCT) had an overall objective response rate of 75% and 34% of the patients went into complete remission (CR). The median duration of response for all responding patients was 6.7 months, and the median duration of response for patients achieving a CR was 20.5 months. The estimated 12-month overall survival for all patients was 89 percent. J Clin Oncol 29: 2011 (suppl; abstr 8031). In the second phase II trial, of the 58 patients with relapsed or refractory systemic ALCL, 86% achieved an objective response and 57% went into CR. The median duration of overall objective response was 12.6 months and the median duration of response for patients achieving a CR was 13.2 months. Median overall survival had not been reached. J Clin Oncol 29: 2011 (suppl; abstr 8032). Brentuximab was very well tolerated with the most common adverse event being peripheral sensory neuropathy. Based on these data, the Oncologic Drugs Advisory Committee (ODAC) voted 10-0 to recommend that the FDA grant accelerated approval of brentuximab vedotin. The results from the above two studies will change the treatment paradigm in this difficult to treat patient population.
Brentuximab vedotin (SGN-35) for Hodgkin’s Lymphoma and Anaplastic large Cell Lymphoma
Brentuximab vedotin (SGN-35) is an antibody-drug conjugate (ADC) that targets CD30, which is a protein expressed on cancer cells in patients with Hodgkin’s lymphoma (HL) as well as Anaplastic Large Cell Lymphoma (ALCL), an aggressive type of T-cell non-Hodgkin’s lymphoma. This ADC consists of an anti-CD30 monoclonal antibody linked to monomethyl auristatin E (MMAE), an antimicrotubule agent. Upon binding to the CD30 molecule on the cancer cells, MMAE is released into the cancer cell resulting in cell death.
Taking advantage of this dual action, targeted mechanism of action of brentuximab vedotin , two phase II studies were conducted, one in patients with relapsed or refractory HL and the other in patients with relapsed or refractory systemic ALCL. In the HL pivotal trial, 102 relapsed or refractory Hodgkin lymphoma patients who had failed prior autologous stem cell transplant (ASCT) had an overall objective response rate of 75% and 34% of the patients went into complete remission (CR). In the second phase II trial, of the 58 patients with relapsed or refractory systemic ALCL, 86% achieved an objective response and 57% went into CR.
Based on these data, the Oncologic Drugs Advisory Committee (ODAC) voted 10-0 to recommend that the FDA grant accelerated approval of brentuximab vedotin. The results from the above two studies will change the treatment paradigm in this difficult to treat patient population.
Exemestane for Breast-Cancer Prevention in Postmenopausal Women
SUMMARY: Breast cancer is the second most common cause of death in the United States. Presently two Selective Estrogen Receptor Modulators (SERM’s), tamoxifen and raloxifene are approved by the FDA, for the primary prevention of breast cancer. Tamoxifen has been associated with increased risk of venous thromboembolism and endometrial cancers. Raloxifene can also be associated with venous thromboembolism but has not been associated with endometrial cancers. Exemestane is an irreversible, steroidal aromatase inactivator. This agent was evaluated in a randomized, placebo controlled, double blind study, to reduce the risk of invasive breast cancer in postmenopausal women, considered to be at moderately increased risk of developing breast cancer. Risk factors included age over 60 years, Gail five year risk score greater than 1.66% and prior atypical ductal/ lobular hyperplasia, LCIS, or DCIS with mastectomy. At a median follow up of 3 years, exemestane reduced the relative incidence of invasive breast cancers by 65% compared to placebo and this benefit was accomplished without serious toxicities and with minimal changes in quality of life. This is the first aromatase inhibitor/inactivator to demonstrate proven efficacy in breast cancer prevention, in a randomized clinical trial. N Engl J Med 2011; 364:2381-2391
Breast Cancer Prevention
Exemestane is an aromatase inactivator presently approved by the FDA for the treatment of breast cancer. This drug was studied in a large randomized clinical trial for the prevention of breast cancer. The results of this study were published in the June 23 issue of the NEJM. Exemestane reduced the relative incidence of invasive breast cancer by 65%, in postmenopausal women with moderate risk of developing breast cancer. The benefit with this drug was accomplished without any significant serious toxicities.
Breast Cancer is the second most common cause of cancer death in the United States. This new addition will be additional ammunition, in the fight against breast cancer
BRAF Mutations in Hairy-Cell Leukemia
SUMMARY: Hairy cell leukemia (HCL) is a relatively indolent disorder with characteristic immunophenotypic findings. In spite of the lack of clear understanding of the molecular biology of HCL, treatment with purine nucleoside analogs has resulted in long term remissions and cure. To under the genetic abnormalities in patients with HCL, Tiacci and colleagues evaluated the peripheral blood of 48 patients with HCL. They noted that all 48 patients had BRAF V600E mutation. This is the same mutation that has been noted in approximately 50% of the patients with melanoma. They further tested the peripheral blood of 5 patients in vitro with BRAF inhibitor vemurafenib. This drug indeed demonstrated efficacy by markedly decreasing phosphorylated ERK and MEK. This interesting finding may help us better understand the pathogenesis of HCL and targeted therapy with BRAF inhibitors may change the way we treat patients with HCL. N Engl J Med 2011; 364:2305-2315
Phase III randomized, open-label, multicenter trial (BRIM3) comparing BRAF inhibitor vemurafenib with dacarbazine (DTIC) in patients with V600E BRAF-mutated melanoma
SUMMARY: The Mitogen- Activated Protein kinase pathway (MAP kinase pathway) is a key signaling pathway which enables the cell to respond external stimuli. There are a number of MAP kinase pathways which share different proteins at each step. The MAP kinase pathway plays a dual role regulating cytokine production and participating in cytokine dependent signaling cascade. The MAP kinase pathway of interest is the RAS-RAF-MEK-ERK pathway. The RAS family of kinases includes ARAF, BRAF and CRAF signaling molecules. BRAF is a very important intermediary of the RAS-RAF-MEK-ERK pathway. BRAF mutations have been demonstrated in 6%-8% of all malignancies. The most common BRAF mutations in melanoma is at the V600E site and is detected in approximately 50% of melanomas. Vemurafenib is a novel oral inhibitor of mutated BRAF. Based on the impressive phase I and phase II data, BRIM 3, a randomized, open-label, multicenter, phase III trial was conducted, in treatment naïve patients with unresectable Stage IIIC or Stage IV melanoma with V600E BRAF mutation. Patients in this trial received either Vemurafenib or Dacarbazine. The primary end points were progression- free survival and overall survival . There was a statistically significant improvement both in progression free survival and overall survival in the Vemurafenib group compared to those in the Dacarbazine group.This is a major advance in the field of personalized medicine and molecular targeted therapy. J Clin Oncol 29: 2011 (suppl; abstr LBA4)
Improving Survival in Metastatic Melanoma
Approximately 50% of the patients with melanoma have an activating BRAF mutation, V600E. Vemurafenib is an oral BRAF kinase inhibitor. In a randomized phase III study involving treatment naive patients with unresectable stage III or stage IV melanoma patients with BRAF mutation V600E, Vemurafenib significantly improved progression free survival (PFS) and overall survival (OS) compared to Dacarbazine (DTIC). This is a major advance in the field of personalized medicine and molecular targeted therapy. This information was presented at the 2011 ASCO meeting.
Iniparib plus Chemotherapy in Metastatic Triple-Negative Breast Cancer
SUMMARY: Patients with triple negative breast cancer have inherent defects in several DNA repair pathways. These cancer cells therefore become increasing dependent on another DNA damage repair pathway called base excision repair (BER) pathway, for survival. It so happens that PARP 1(PolyAdenosine diphosphate Ribose Polymerase) is an important enzyme regulating the BER pathway. By inhibiting PARP1, the BER pathway is inhibited leading to extreme levels of DNA damage and eventual death of cancer cells. In an article published in the January, 2011 issue of the NEJM, the addition of a PARP inhibitor Iniparib to chemotherapy improved clinical benefit and survival of patients with advanced triple negative breast cancer. A phase II open label trial was conducted, in which 123 patients with metastatic triple negative breast cancer were randomly assigned to receive a combination of carboplatin and GEMZAR® (gemcitabine) with or without iniparib. Patients who received chemotherapy in combination with iniparib demonstrated improved rate of clinical benefit (partial or complete response plus stable disease for 6 or more months) from 34% to 56% (P=0.01). This was the primary end point. The addition of iniparib to chemotherapy also prolonged the median progression free survival from 3.6 months to 5.9 months (HR for progression, 0.59; P=0.01) and median overall survival from 7.7 months to 12.3 months (HR for death, 0.57; P=0.01). These gains were achieved without any significant increase in toxicities. This difficult to treat subtype of breast cancer may soon become extinct. N Engl J Med 2011; 364:205-214