SUMMARY: The CLEOPATRA trial is a phase III trial in which 808 HER positive metastatic breast cancer patients, for their first line treatment, were randomized to either HERCEPTIN® plus Docetaxel or the above two drug combination given along with PERJETA® (Pertuzumab). PERJETA® is a recombinant humanized monoclonal antibody that binds to the HER2 dimerization domain and prevents the dimerization of HER2 with other HER receptors ie. HER3, HER1 and HER4. The addition of PERJETA® to the combination of HERCEPTIN® and Docetaxel significantly prolonged progression-free survival compared to HERCEPTIN® plus Docetaxel alone (18.5 months vs 12.4 months, P<0.001). This benefit was seen without increase in cardiotoxicity. It appears that PERJETA® complements HERCEPTIN® in targeting HER-2 receptor. Baselga J, Cortés J, Kim S, et al. N Engl J Med 2012; 366:109-119
Author: RR
Radiotherapy with or without Chemotherapy in Muscle-Invasive Bladder Cancer
SUMMARY: In this phase III trial, 360 patients with muscle-invasive bladder cancer were randomized to receive radiation therapy with or without concurrent chemotherapy. The chemotherapy regimen consisted of 5-fluorouracil given on days 1-5 and days16-20 of radiotherapy and mitomycin C given on day 1. The primary end point of this study was locoregional disease free survival. Secondary end points included overall survival and toxicities. The locoregional disease–free survival at two years was 67% in the chemoradiation group and 54% in the radiation therapy only group. With a median follow-up of 69.9 months, the hazard ratio in the chemoradiation group was 0.68 (P=0.03). The overall survival at five years was 48% in the chemoradiation group and 35% in the radiation therapy only group with a hazard ratio of 0.82 (P=0.16). The authors concluded that for patients with muscle invasive bladder cancer, concurrent chemoradiation significantly improved locoregional disease free survival compared to radiation therapy only. James ND, Hussain SA, Hall E, et al. N Engl J Med 2012; 366:1477-1488
ZALTRAP® for second line treatment of metastatic CRC
ZALTRAP® (Aflibercept) is a soluble fusion protein that is capable of binding with high affinity to pro-angiogenic factors such as all VEGF-A isoforms, VEGF-B, and PlGF. This is unlike bevacizumab, which is a monoclonal antibody that only targets all isoforms of VEGF-A. In the VELOUR trial, second-line chemotherapy in combination with ZALTRAP® (Aflibercept) demonstrated significant improvement in the progression-free survival as well as overall survival compared to chemotherapy alone. This benefit was seen irrespective of prior bevacizumab therapy. This data was presented at the 13th ESMO world congress.
Regorafenib improves survival in advanced CRC
The CORRECT trial is a randomized phase III study which demonstrated improved survival with Regorafenib, an oral multikinase inhibitor when compared to placebo, in individuals with advanced colorectal cancer, who had progressed on all available standard therapies. This important study gives a new option for individuals with advanced colorectal cancer. Additional data will be presented at ASCO 2012 meeting.
Intravenous (IV) aflibercept versus placebo in combination with irinotecan/5-FU (FOLFIRI) for second-line treatment of metastatic colorectal cancer (MCRC) Results of a multinational phase 3 trial (EFC10262-VELOUR)
SUMMARY:ZALTRAP® (Aflibercept) is a soluble fusion protein that is capable of binding with high affinity to pro-angiogenic factors such as all VEGF-A isoforms, VEGF-B, and PlGF. This is unlike bevacizumab, which is a monoclonal antibody that only targets all isoforms of VEGF-A. VELOUR is a phase III trial in which 1,226 patients who had failed oxaliplatin-based therapy received second-line therapy and the comparison was FOLFIRI (leucovorin, fluorouracil, irinotecan) with or without ZALTRAP® (Aflibercept). With a median follow-up of 22.3 months, there was significant improvement in the progression-free survival noted in the ZALTRAP® (Aflibercept) group (6.9 vs 4.67 months; HR = 0.758;P = .00007) as well as overall survival (13.5 vs 12.06 months; HR = 0.817;P = .0032). This benefit was seen irrespective of prior bevacizumab therapy. The authors did point out that in the E3200 Intergroup trial, which tested second-line FOLFOX4 chemotherapy with or without bevacizumab, all of the patients were bevacizumab-naive, whereas 70% in the VELOUR trial were bevacizumab-naive.Van Cutsem E, Tabernero J, Lakomy R, et al. Results of a multinational phase 3 trial (EFC10262-VELOUR). 13th ESMO World Congress on Gastrointestinal Cancer. Abstract 0-0024.
CLEOPATRA Trial in Breast Cancer
In this Phase III trial involving first line treatment of patients with HER-2 positive metastatic breast cancer, the addition of Pertuzumab (an anti-HER-2 humanized monoclonal antibody that inhibits receptor dimerization) to a combination of Trastuzumab and Docetaxel significantly prolonged progression-free survival, without increase in cardiotoxicity when compared to Trastuzumab and Docetaxel alone. It appears that Pertuzumab complements Trastuzumab in targeting HER-2 receptor.
These findings from the CLEOPATRA trial have demonstrated that comprehensive HER-2 blockade may result in improved outcomes for patients with breast cancer over expressing HER-2.
The original article was published in the January 2012 issue of the NEJM.
OncoPrescribe Newsletter
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.
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.
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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.