1 / 61

RTP TV: An 8-Part Live CME Webcast Series

Joyce O'Shaughnessy, MD Co-Director, Breast Cancer Research ProgramBaylor-Charles A Sammons Cancer CenterTexas Oncology, PAUS OncologyDallas, Texas. Eric P Winer, MDThompson Investigator in Breast Cancer ResearchChief, Division of Women's Cancers Dana-Farber Cancer InstituteProfessor of MedicineHarvard Medical SchoolBoston, Massachusetts.

tanuja
Télécharger la présentation

RTP TV: An 8-Part Live CME Webcast Series

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

    1. RTP TV: An 8-Part Live CME Webcast Series

    3. Disclosures for Moderator Neil Love, MD

    4. Disclosures for Joyce OShaughnessy, MD

    5. Disclosures for Eric P Winer, MD

    6. RTP TV: An 8-Part Live CME Webcast Series

    7. Survey of 100 Practicing Oncologists 95% fraction who see patients with TNBC 10 median number of patients with metastatic TNBC currently in their practices

    8. Survey of 100 Practicing Oncologists Fraction with a patient who has received Iniparib 23% Olaparib 16% Veliparib 7%

    9. Survey of 100 Practicing Oncologists If you were to attend a CME conference on breast cancer, to what extent would you be interested in learning about the following topics? Response scale 0 10 0 = no interest 10 = very interested

    10. TNBC: New Agents and Regimens

    11. TNBC: PARP Inhibitors

    12. Survey of 100 Practicing Oncologists What question(s) would you like to pose to a clinical investigator with expertise in the management of TNBC? 97 questions/cases received

    13. When will newer agents be integrated into earlier lines of treatment?

    14. When is BRCA testing indicated in a patient with TNBC?

    15. Under what conditions should metastatic sites be biopsied?

    16. Are there other new noncytotoxic, targeted agents in TNBC in addition to PARP inhibitors? Naples, FL

    18. Case 1 (Dr OShaughnessy) 50 yo woman with basal-like TNBC Preoperative AC ? paclitaxel: pCR Tumor melts away after 1 cycle of AC Locoregional RT 2 years later, very rapidly growing ipsilateral internal mammary node protruding from her chest and invading sternum and mediastinal LNs Patient enrolls on a trial of gem/carbo iniparib* Major response for 8 cycles (6 months) Tissue harvested for total genome sequencing Paclitaxel/bevacizumab Response for 6 months but progressing

    19. Progression with Regrowth of Ipsilateral Mammary Mass and Mediastinal Nodes

    20. Phase II Study of Iniparib plus Gemcitabine/Carboplatin in mTNBC

    21. A Randomized Phase III Study of Iniparib (BSI-201) in Combination with Gemcitabine and Carboplatin in Metastatic Triple-Negative Breast Cancer (mTNBC) OShaughnessy J et al. Proc ASCO 2011;Abstract 1007.

    22. Phase II Study of Iniparib plus Gemcitabine/Carboplatin in mTNBC

    23. Metastatic Triple-Negative Breast Cancer (mTNBC) 15% of breast cancers; clinically defined as ER-negative, PR-negative and HER2-non-overexpressing Heterogeneous disease with generally virulent natural history Shares gene expression profiles with basal-like, claudin-low and other molecular subtypes No clinical implications of molecular subtypes at present

    24. Iniparib (BSI-201) A novel, investigational, anticancer agent In triple-negative breast cancer cell lines: Induces cell cycle arrest in the G2/M phase Induces double strand DNA damage ?H2AX foci but does not inhibit PARP1 and 2 at physiologic drug concentrations Potentiates cell-cycle arrest induced by DNA damaging agents, including platinum and gemcitabine Physiologic targets of iniparib and its metabolites are under investigation

    25. Preclinical Pharmacodynamic and Pathway Analysis of 3 Presumed PARP Inhibitors: ABT-888, AZD2281, BSI-201 ABT-888 and AZD2281 are mediated by PARP1 or PARP2. Iniparib (BSI-201) suppressed genes in the telomere pathway, suggesting PARP5/6 as potential targets.

    26. Schema

    27. Study Objectives Primary: Coprimary endpoints: Overall survival (OS) Progression-free survival (PFS) Study considered positive if either endpoint met Secondary: Objective response rate (ORR) Safety, tolerability and pharmacokinetics of GCI

    28. Treatment-Emergent Adverse Events Safety Population (Prior to crossover, >5% Grade 3/4 in GCI arm)

    36. Deconstructing the molecular portraits of breast cancer

    41. Case 2 (Dr Winer) 48 yo premenopausal, BRCA1/2-negative woman presents 6 years ago with weakly ER+, PR- T2N1 breast cancer Neoadjuvant AC ? paclitaxel Excision/re-excision plus RT Tamoxifen Ipsilateral breast recurrence 1 year later Mastectomy Waxing and waning supraclavicular adenopathy over next 18 months until diagnosed with local recurrence Needle biopsy reveals metastatic TNBC, with small pulmonary nodule Enrolled on TBCRC009: Phase II study of cisplatin or carboplatin for metastatic TNBC* Clinical CR after 7 cycles of cisplatin Treatment discontinued due to toxicity (fatigue, neuropathy) No further therapy for past 2 years, 4 months

    43. TBCRC009: A Multicenter Phase II Study of Cisplatin or Carboplatin for Metastatic Triple-Negative Breast Cancer and Evaluation of p63/p73 as a Biomarker of Response

    44. Phase II Study of Cisplatin or Carboplatin for mTNBC 86 patients enrolled to physician's choice of either cisplatin or carboplatin Overall RR: 30.2%, including 4 CR (4.7%) and 22 PR (25.6%) RR by treatment (exploratory): 37% cisplatin 23% carboplatin p63/p73 analysis is ongoing

    45. Submitted Case Dr Frances de la Serna, Philippines 40 yo woman with axillary lymphadenopathy in 1/2010 Excisional biospy: Ductal carcinoma consistent with breast primary in 4 nodes Ultrasound: 2 solid masses in breast (15.1 and 20.9 mm) Neoadjuvant anthracycline/taxane-based therapy x 2 cycles ? surgery No residual tumor or LVI in the breast 7/9 nodes positive ER/PR-, HER2 1-2+ (FISH positive) Receives chemotherapy/trastuzumab

    46. Submitted Case (Continued) 12/2010: Neck mass FNB: Metastatic carcinoma Multiple enlarged lymph nodes in supraclavicular and jugular chains Excisional biopsy: ER/PR/HER2-negative adenocarcinoma Patient receives cisplatin/gemcitabine Resolution of enlarged nodes 5/2011: Neck mass Biopsy: Metastatic carcinoma Multiple nodules on the skin flap Plan: Continue cisplatin

    47. Local versus Central Laboratory Discrepancies in TNBC Status (CIBOMA/2004-01/GEICAM/2003-11) N = 1,441 patient samples sent for central laboratory confirmation In 130 cases (9%) tumors were found to not be TNBC by central determination 71% of discrepant results involved ER or PR status 22% of discrepant results involved HER2 status

    51. TBCRC 018: Phase II Study of Iniparib plus Chemotherapy to Treat Triple-Negative Breast Cancer (TNBC) Brain Metastases (BM) Anders CK et al. Proc ASCO 2011;Abstract TPS127: Trials in Progress.

    54. Case 3 (Dr OShaughnessy) A woman in her mid-50s with locally advanced and metastatic TNBC Enrolled in a study of total genome sequencing Determined to have a high level BRAF amplicon Enrolled on a Phase I trial of MEK plus AKT inhibitors* Significant response in a very large, fungating breast

    58. A Phase I Dose-Escalation Study of Oral MK-2206 (Allosteric AKT Inhibitor) with Oral Selumetinib (MEK Inhibitor) in Patients with Advanced or Metastatic Solid Tumors

    61. Schedule of Events

More Related