TARCEVA® (Erlotinib): The FDA on May 14, 2013 approved TARCEVA® for the first-line treatment of metastatic non-small cell lung cancer (NSCLC) patients whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. The FDA concurrently approved the cobas EGFR Mutation Test, a companion diagnostic test for detection of these molecular abnormalities. TARCEVA has had prior FDA approval for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen and for maintenance treatment of patients with locally advanced or metastatic NSCLC, whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. TARCEVA® is a product of Astellas Pharma Inc.
Author: RR
MYELOMA – mSMART is the way to go
Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) developed by the Mayo Clinic, unlike the present staging systems takes cytogenetic features into consideration and stratifies patients into High risk, Intermediate risk and Low risk groups. The clinician, based on the risk, then decides on the most appropriate therapy. This Risk-Adapted Therapy should result in better outcomes without compromising care. The 2013 mSMART Consensus Guidelines were published in the April issue of the Mayo Clinic Proceedings.
TTP, HUS and aHUS Different diseases – Different treatments
SUMMARY: Thrombotic Thrombocytopenic Purpura (TTP), Hemolytic Uremic Syndrome (HUS) and Atypical Hemolytic Uremic Syndrome (aHUS) are Thrombotic Microangiopathies (TMA’s) associated with MicroAngiopathic Hemolytic Anemia and thrombocytopenia. Even though their clinical presentation has some similarities, they are distinct entities with different pathophysiology and hence managed differently. With the identification of von Willebrand Factor (vWF) cleaving protease ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) in 1996, we are now able to better understand and appropriately manage these TMA’s. Patients with TTP are deficient in ADAMTS13 and therefore develop platelet microthrombin in small blood vessels due to uninhibited propagation of platelet aggregates bound to ultra high molecular weight VWF multimers. Approximately 10% or less of Shiga-Toxin producing Escherichia Coli (STEC) infections may be associated with HUS. aHUS is caused by a genetic deficiency of one or more complement regulatory proteins which results in uncontrolled activity of the alternate complement pathway. Plasma Exchange in TTP restores the protease activity of ADAMTS13 whereas aHUS is treated with SOLIRIS® (Eculizumab) to inhibit complement mediated TMA. Once a diagnosis of STEC-HUS is confirmed, hospitalization and intensive care with transfusions and kidney dialysis may become necessary. George JN. Blood 2010:116; 4060-4069
Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID) an international, multicentre, randomised, placebo-controlled, phase 3 trial
SUMMARY: STIVARGA® (Regorafenib) is an oral multikinase inhibitor. In this international trial, 199 patients with advanced GIST who had progressed on both GLEEVEC® (Imatinib) and SUTENT® (Sunitinib) were randomized in a 2:1 ratio to receive either STIVARGA® or placebo. The primary endpoint was progression-free survival (PFS). Patients in the STIVARGA® group had a statistically significant 3.9 month improvement in progression-free survival (PFS) compared to placebo (4.8 months vs 0.9 months; Hazard Ratio = 0.27; P<.0001). Following progression, 85% of the patients assigned to the placebo group crossed over to the STIVARGA® group. Treatment was well tolerated and the most common adverse events included hypertension, hand-foot syndrome and diarrhea. There is now a new treatment option for patients with GIST who progress on GLEEVEC® and SUTENT®. Demetri GD, Reichardt P, Kang Y, et al. The Lancet. 2013;381:295-302
STIVARGA® (Regorafenib)
The FDA on February 25, 2013 approved the use of STIVARGA® for the treatment of patients with advanced GastroIntestinal Stromal Tumors (GIST) that are unresectable or metastatic and are no longer responding to GLEEVEC® (Imatinib) and SUTENT® (Sunitinib). The FDA initially approved STIVARGA® in 2012 for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine, ELOXATIN® (Oxaliplatin), and CAMPTOSAR® (Irinotecan) based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. STIVARGA® is a product of Bayer HealthCare Pharmaceuticals, Inc.
STIVARGA® (Regorafenib) for advanced GIST
STIVARGA® is an oral multikinase inhibitor. In a study published in the January 2013 issue of THE LANCET, treatment with STIRVAGA® in patient population resistant or refractory to GLEEVEC® and SUTENT® resulted in significant improvement in progression free survival. This is the third agent approved by the FDA for advanced GIST. As patients with advanced GIST live longer, newer agents with unique mechanism of action will take center stage.
KADCYLA® (Ado-Trastuzumab Emtansine, T-DM1):
The FDA on February 22, 2013 approved KADCYLA® for the treatment of patients with HER2-positive metastatic breast cancer who have received prior treatment with HERCEPTIN® (Trastuzumab) and a Taxane chemotherapy. KADCYLA® is marketed by Genentech U.S., Inc.
Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane.
SUMMARY: The HER or erbB family of receptors consist of HER1,HER2,HER3 and HER4. Overexpression of HER2 in breast cancer has been associated with higher risk for relapse as well as overall survival. HERCEPTIN® (Trastuzumab) is a humanized monoclonal antibody targeting HER2. It binds to the extracellular domain of the receptor and blocks the downstream cell signaling pathways. KADCYLA® (Ado-Trastuzumab Emtansine, T-DM1) is an antibody-drug conjugate (ADC) comprised of the antibody Trastuzumab and the chemotherapy agent Emtansine, linked together. It inhibits HER2 signaling and destroys the HER2-positive tumor cells by delivering the chemotherapy agent Emtansine which binds to tubulin, directly inside the tumor cells. The EMILIA trial is a phase III study in which 991 patients with HER2-positive locally advanced or metastatic breast cancer who had previously received treatment with HERCEPTIN® and a Taxane chemotherapy, were enrolled. Patient received either KADCYLA® or XELODA® (Capecitabine) and TYKERB® (Lapatinib) doublet. The primary endpoints were Progression Free Survival (PFS), Overall Survival (OS) and safety. Patients receiving KADCYLA® had an improved PFS compared to XELODA® and TYKERB® (9.6 months vs 6.4 months, HR=0.65, P <0.0001). The median overall survival was 30.9 months in the KADCYLA® group and 25.1 months with the XELODA® and TYKERB® doublet. KADCYLA® is the fourth drug approved by the FDA, that targets the HER2 oncogene. The other FDA-approved drugs used to treat HER2-positive breast cancer include HERCEPTIN® (1998), TYKERB® (2007) and PERJETA® (Pertuzumab) (2012). Blackwell KL, Miles D, Gianni L, et al. J Clin Oncol 30, 2012 (suppl; abstr LBA1)
KADCYLA® (Ado-Trastuzumab Emtansine, T-DM1) now approved
The FDA today approved KADCYLA® for the treatment of patients with HER2-positive metastatic breast cancer who have received prior treatment with HERCEPTIN® (Trastuzumab) and a taxane chemotherapy. In a large Phase III trial, KADCYLA® improved Progression Free Survival as well as Overall Survival compared to XELODA® (Capecitabine) and TYKERB® (Lapatinib). KADCYLA® is the fourth drug approved by the FDA, that targets the HER2 oncogene. The other FDA-approved drugs used to treat HER2-positive breast cancer include HERCEPTIN® (1998), TYKERB® (2007) and PERJETA® (Pertuzumab) (2012).