SUMMARY:The HER or erbB family of receptors consist of HER 1,HER 2,HER 3 and HER 4. Overexpression of HER 2 in breast cancer has been associated with higher risk for relapse as well as overall survival. Trastuzumab is a humanized monoclonal antibody targeting HER 2. It binds to the extracellular domain of the receptor and blocks the downstream cell signaling pathways. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) comprised of the antibody trastuzumab and the chemotherapy agent DM1 linked together and inhibits HER2 signaling and destroys the HER2-positive tumor cells by delivering the chemotherapy agent DM1 directly inside the tumor cells. The EMILIA trial is a phase III study in which 978 patients with HER2-positive locally advanced or metastatic breast cancer who had previously received treatment with HERCEPTIN® (Trastuzumab) and a taxane chemotherapy, were enrolled. Patient received either trastuzumab emtansine (T-DM1) or XELODA® (Capecitabine) and TYKERB® (Lapatinib) doublet. The primary endpoints were Progression Free Survival (PFS), Overall Survival (OS) and safety. Patients receiving T-DM1 had an improved PFS compared to XELODA® and TYKERB® (9.6 months vs 6.4 months, HR=0.65, P <0.0001). A final OS analysis will be available at a later date. Blackwell KL, Miles D, Gianni L, et al. J Clin Oncol 30, 2012 (suppl; abstr LBA1)
Category: Meeting Updates
Effect of MDV3100, an androgen receptor signaling inhibitor (ARSI), on overall survival in patients with prostate cancer post docetaxel Results from the phase III AFFIRM study
SUMMARY: MDV3100 is an androgen receptor antagonist with a significantly higher binding affinity for the androgen receptor (AR) compared to the antiandrogen bicalutamide and there by competitively inhibits the binding of androgens to the androgen receptor. Majority of the patients with advanced prostate cancer become refractory to hormone therapy because of increased production of androgen receptors by the tumors as well as mutated androgen receptors. The superiority of this novel agent, MDV3100, is based on the fact that the expression of androgen dependent genes are downregulated with MDV 3100 leading to cell death or apoptosis, whereas with bicalutamide the expression of these genes are upregulated. Further MDV3100 continues to antagonize mutated androgen receptors on the prostate tumor cells in contrast to bicalutamide which behaves as an agonist. It is thus an androgen receptor signaling inhibitor (ARSI). The AFFIRM clinical trial is a randomized, multinational phase III study in which patients who had received prior docetaxel-based chemotherapy regimens were randomized 2:1 to receive either MDV3100, 160 mg/day or placebo. Patients treated with MDV3100 had a median survival of 18.4 months, compared with 13.6 months for men treated with placebo, with a median OS advantage of 4.8 months and a reduction in the risk of death by 37%. Scher HI, Fizazi K, Saad F, et al. J Clin Oncol 30, 2012 (suppl 5; abstr LBA1)
Results of a phase III randomized, double-blind, placebo-controlled, multicenter trial (CORRECT) of regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after standard therapies
SUMMARY: In this phase III trial, patients with metastatic colorectal carcinoma who had progressed after approved standard therapies were randomly assigned in a 2:1 ratio to receive either Regorafenib, an oral multikinase inhibitor plus best supportive care or placebo plus best supportive care. Seven hundred and sixty patients were randomized. Patients receiving Regorafenib had a statistically significant improvement in the overall survival and progression free survival compared to placebo, without any unexpected toxicities. This important study gives a new option for individuals with advanced colorectal cancer who have progressed on all available standard therapies. Grothey A, F. Sobrero AF, Siena S, et al. J Clin Oncol 30, 2012 (suppl 4; abstr LBA385)
Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first progression in patients with metastatic colorectal cancer (mCRC) previously treated with BEV plus CT Results of a randomized phase III intergroup study (TML study)
SUMMARY:The ML18147 (TML) is a randomized phase III trial in which patients who received AVASTIN® (Bevacizumab) plus standard chemotherapy as initial treatment (first-line treatment) for their metastatic colorectal cancer were then randomized to either continue AVASTIN® with a different chemotherapy after their cancer progressed (second-line treatment) or receive the different chemotherapy regimen without AVASTIN®. Patient group continuing AVASTIN® as a part of second line treatment demonstrated an improved survival compared to those who received chemotherapy alone, as second line treatment. This study has demonstrated that continuing AVASTIN® with second line chemotherapy post progression, extends survival in patients with metastatic colorectal cancer. Arnold D, Andre T, Bennouna J, et al. J Clin Oncol 30, 2012 (suppl; abstr CRA3503)