Cancer Pharmacogenomics: Setting a Research Agenda to Accelerate Translation

Slide 1 of 9: Applications of Cancer Pharmacogenomics in a Naturalistic Setting

Robert S. Epstein, M.D., M.S.
Chief Medical Officer
Medco

July 21, 2009


Slide 2 of 9:

Naturalistic setting of Medco

  • Supports PPWG preliminary recommendations

Retrospective database research possibilities

  • Extend prior research
  • Expand size, outcomes
  • Supply information about ‘usual care’ patients

Prospective research/programs

  • Adoption statistics – clinician, patients
  • Population-based prevalence numbers

Slide 3 of 9: Relation to Comparative Effectiveness Research (CER)

“Compare the effectiveness of genetic and biomarker testing and usual care in preventing and treating breast cancer..…”

Key Elements¹

  • Direct comparison of effective interventions
  • Study of patients in typical day-to-day clinical care
  • Aim to tailor decisions to the needs of individual patients

¹Source: Institute of Medicine Report Brief June 2009: Initial national priorities for comparative effectiveness research


Slide 4 of 9: Naturalistic Setting of Medco

Pharmacy and a database system

  • 2200 pharmacists serve ~8 million US lives
  • Wired pharmacies (all 60,000) serve an additional ~ 55+ million US lives
  • On ~20 million lives – longitudinal data on hospitalizations, labs, visits, procedures and coding for diagnoses linked with prescription data

Slide 5 of 9: Retrospective Study and Pharmacogenomics: Example of Phenocopying a Genetic Mutation

Increased risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors by R. E. Aubert¹, E. J. Stanek¹, J. Yao,¹ J. R. Teagarden¹, M. Subar¹, R. S. Epstein¹, T. C. Skaar², Z. Desta², D. A. Flockhart²;

¹Medco Health Solutions, Franklin Lakes, NJ; ²Indiana University School of Medicine, Indianapolis, IN. Presented at ASCO June 2009.


Slide 6 of 9: Background

Hepatic cytochrome P450 2D6 (CYP2D6) is key in metabolic activation of tamoxifen to its active metabolite, endoxifen.

Previous studies have shown that women receiving tamoxifen who have reduced-function CYP2D6 polymorphisms and are poor metabolizers have lower levels of endoxifen and higher recurrence rates.

Previous small studies with CYP2D6 inhibitors and tamoxifen show reductions in endoxifen (45-58%), but have not delineated their impact on breast cancer recurrence.


Slide 7 of 9: Study Design

Retrospective cohort analysis of medical and pharmacy claims from a 10 million-member Integrated Database (Medco Health Solutions, Inc)

  • ICD-9 and CPT-4 codes

Study Population:

  • Women who initiated tamoxifen therapy 07/01/2003 - 12/31/2005

Inclusion criteria:

  • Continuously eligible 6-months prior to initiating tamoxifen
  • Tamoxifen-naïve (6-month negative history)
  • Tamoxifen persisting at least 24 months post-initiation and reasonable level of adherence (MPR ≥ 0.70)
  • Diagnosis of breast cancer

Slide 8 of 9: CYP2D6 Inhibitor Exposure Cohorts

Cohort stratification based on therapy received at any time over initial 24 months of follow-up after initiating tamoxifen therapy determined to be a CYP2D6-inhibitor by any of 4 reference documents

No CYP2D6-inhibitor Exposure

  • Patients with no prescription claim for a drug considered CYP2D6 inhibitor at anytime during the follow-up period

CYP2D6-inhibitor Exposure

  • CYP2D6 inhibitor with overlapping days of therapy with tamoxifen

Slide 9 of 9: Primary End Point

Follow-up measurement starts 6-months post-initiation of therapy and continued through 12/31/2007

Hospitalization for breast cancer during the follow-up period (determined by ICD-9 and CPT-4 codes)

  • Breast cancer diagnosis or one or more of the following procedures:
    • Lumpectomy
    • Partial mastectomy
    • Lymph node dissection
    • Mastectomy
    • Radiation therapy

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