ASCO: A Focus on Personalized Medicine

Anna Azvolinsky, PhD
Published: Wednesday, May 30, 2012
Patricia LoRusso

Patricia LoRusso, DO

The year 2011 marked a milestone of sorts for new drug approvals by the FDA. Thirty-five new medicines were approved—the second highest number of approvals in the last decade. Seven were oncology drugs, including the first one approved for Hodgkin lymphoma in 30 years. With the influx of these new drugs, awareness and education for oncologists are paramount, and this year’s annual meeting of the American Society of Clinical Oncology (ASCO) will include educational seminars on these latest clinical advances. Leading researchers involved in the development of the oncology drugs will provide practical advice on individual new therapies.

  • Vemurafenib (Zelboraf, Genentech), an oral, small-molecule BRAF inhibitor for patients with metastatic melanoma whose tumors harbor a BRAFV600E mutation.
  • Crizotinib (Xalkori, Pfizer), an oral, small-molecule, dual inhibitor of the c-MET and ALK receptor tyrosine kinases for advanced non-small cell lung cancer (NSCLC) that expresses the EML4-ALK fusion gene.
  • Brentuximab vedotin (Adcetris, Seattle Genetics), for intravenous infusion, an anti-CD30 antibody for the treatment of CD30-positive relapsed Hodgkin lymphoma and relapsed systemic anaplastic large cell lymphoma.
  • Abiraterone acetate (Zytiga, Janssen), an oral inhibitor of the cytochrome P450 17A1 protein (CYP17A1) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in men who have received prior chemotherapy.
  • Axitinib (Inlyta, Pfizer), an oral small-molecule inhibitor of multiple tyrosine kinases including cKIT, VEGFR 1-3, and PDGFR, for treatment of relapsed advanced renal cell carcinoma (RCC).
  • Vismodegib (Erivedge, Genentech), an oral inhibitor of the Hedgehog pathway for the treatment of advanced basal cell carcinoma (BCC). Uninhibited signaling of the Hedgehog pathway is the molecular driver of BCC.
  • Targeted Therapy Presentations to Watch for at ASCO

    Metastatic melanoma: Results of the phase III METRIC clinical trial of trametinib, a MEK inhibitor tested in a global, randomized trial of patients with metastatic melanoma, the results of the phase III BREAK-3 trial of dabrafenib, a BRAF kinase inhibitor; also, an update on a phase I/II trial of dabrafenib combined with trametinib in treatment-naïve patients.

    RCC: Results of the global, randomized, phase III TIVO-1 clinical trial testing the efficacy of tivozanib, a receptor tyrosine kinase inhibitor, against sorafenib, the current standard of care, as a first-line treatment for advanced RCC.

    Liver cancer, RCC, prostate cancer, and thyroid cancer: Four oral presentations of studies with cabozantinib (XL184) are expected during ASCO. Cabozantinib is a small-molecule inhibitor of the tyrosine kinases c-Met and VEGFR2. The four presentations will be:

    • Clinical data of a phase II randomized, discontinuation trial in hepatocellular carcinoma
    • Efficacy of cabozantinib in patients with metastatic, refractory RCC
    • Phase II nonrandomized, expansion cohort results in chemotherapy-pretreated mCRPC
    • Full results of the pivotal phase III EXAM trial in medullary thyroid cancer patients

    Non-small cell lung cancer: Results of the pivotal phase III LUX-Lung 3 trial of afatinib in treatment-naïve patients with metastatic NSCLC with EGFR mutations. The trial compares the efficacy of afatinib, an irreversible ErbB family inhibitor, to pemetrexed/cisplatin. Mutations in EGFR, also known as ErbB1, are found in approximately 12% of Caucasians and as many as 40% of Asian patients with NSCLC.

    Acute myeloid leukemia and acute lymphoblastic leukemia: Six-month follow-up data from the pivotal PACE trial of ponatinib, a pan-BCR-ABL inhibitor, in patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who are resistant or intolerant to the currently approved BCR-ABL inhibitors dasatinib and nilotinib, or who have the T315I mutation. Positive preliminary data were presented at the American Society of Hematology (ASH) meeting in December 2011.

    Immunotherapy for melanoma, RCC, and lung cancer: Several abstracts will be presented on phase I and phase II clinical trials of MDX-1106/ BMS-936558, an anti-PD1 immunotherapy that is seen as the next generation of immunotherapy after ipilimumab. Anti-PD1 is being developed by Bristol-Myers Squibb. Results are expected from the large expansion cohort data of the phase I/II solid tumor trial and potentially from the phase II RCC trial.

    Another pre-meeting session will focus specifically on targeted therapy approaches. Patricia LoRusso, DO, of the Karmanos Cancer Institute, Detroit, Michigan, in the session “Where Did We Come From, Where Do We Go From Here?” will give a bird’s-eye view of targeted therapies, discussing past and present development and how to approach the next phase based on what targeted therapies have taught us thus far. Because many of the new targeted therapies are oral medications that patients take at home, the ways in which patients are educated about their treatments and monitored have fundamentally evolved. The management of side effects of targeted therapies will be discussed in a session by an oncology nurse, Peg Esper, MSN, MSA, RN, ANP-BC, AOCN, from the University of Michigan School of Nursing, Ann Arbor.
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