Twelve-Year Study Update for a Postmarketing Case Series Study of Adult Osteosarcoma and Teriparatide in the US

Transcription

1 June 21, 2017 Twelve-Year Study Update for a Postmarketing Case Series Study of Adult Osteosarcoma and Teriparatide in the US David Harris, MPH RTI Health Solutions Co-authors: Kirk Midkiff, MPH, Alicia Gilsenan, PhD, and Elizabeth Andrews, PhD Presented at the NAACCR 2017 Annual Conference Albuquerque, New Mexico

2 Objectives of Presentation The primary objective of this presentation is to provide a 12- year study update (for diagnosis years ) using results as of March 31,

3 Background What is Forteo (teriparatide)? A medication similar to natural parathyroid hormone It stimulates formation of new bone and increases in bonemineral density and bone strength It is a self-injected daily therapy approved for use for up to 2 years It was initially approved in 2002 in the US for treatment of postmenopausal women with osteoporosis and of men with low bone-mineral density at a high risk of fracture The treatment indication was expanded in 2009 to include glucocorticoid-induced osteoporosis 3

4 Background In rat toxicology studies, teriparatide caused a dose-dependent increase in the incidence of osteosarcoma Subsequent studies demonstrated a no-effect dose in rats No signal was seen in humans during clinical trials As a condition of drug approval, the FDA requested a postapproval surveillance study The US Osteosarcoma Surveillance Study initiated in 2002 is an ongoing 15-year surveillance study Adult osteosarcoma is rare (2-3 cases per million per year among adults) Requirements for contacting the patient ( patient access pathways ) vary by registry from passive notification to active permission from the physician and/or patient 4

5 Osteosarcoma Surveillance Study Objectives Primary objectives: Identify and interview 33% of newly diagnosed cases of osteosarcoma in the US among adults 40 years of age and older at the time of diagnosis Identify incident cases of osteosarcoma with a history of treatment with teriparatide Secondary objective: to systematically collect for descriptive epidemiology purposes additional patient information, including Demographic information Treatment with other medications Comorbid conditions Risk factors for osteosarcoma 5

6 Osteosarcoma Surveillance Study Methods Patients with incident osteosarcoma diagnosed from are identified through participating cancer registries Data collection will conclude on September 30, 2018, and patients will be interviewed through the end of 2018 Once permission requirements are met, registries report cancer diagnosis and contact information to RTI RTI contacts the patient, administers consent, and conducts a minute telephone interview with the patient or the patient s proxy RTI summarizes characteristics using descriptive statistics and prepares a standardized incidence ratio (SIR) 6

7 Definition of the Standardized Incidence Ratio O = Observed number of osteosarcoma cases with confirmed exposure to Forteo E = Expected number of osteosarcoma cases exposed to Forteo, based on Background incidence rate of osteosarcoma in the US Surveillance, Epidemiology, and End Results Program (SEER) estimate, age- and sex-adjusted to the US Forteo population Estimated person-years at risk following first exposure to Forteo Study interview rate The proportion of all estimated osteosarcoma cases diagnosed in the US that have been interviewed by RTI 7

8 Cases Identified * by Registries Participating in the Osteosarcoma Surveillance Study (n = 3,161) *Diagram excludes cases diagnosed from

9 Patient Accrual and Interview Rate as of March 31, 2017 Estimated number of cases not reported to study due to state cancer registry not participating n = 1,017 Total reported to RTI without contact information n = 853 Total not yet meeting patient access requirements n = 105 Total unable to interview n = 739 Total did not consent n = 409 Total osteosarcoma cases expected for diagnosis years N = 4,178 a Total osteosarcoma cases identified by participating registries for diagnosis year n = 3,161 Total osteosarcoma cases reported to RTI with contact information n = 2,308 Total osteosarcoma cases available for contact by an RTI interviewer n = 2,203 Total osteosarcoma patients/proxies consented and interviewed n = 1,046 Total pending interview n = 9 Progress toward meeting 33% study goal Percentage interviewed n = 1,046 of 4,178 (25%) Questionnaire response rate n = 1,046 of 2,203 (47%) Operational metric a Diagram excludes cases diagnosed in 2015 and 2016 due to a 9- to 18-month lag in reporting from participating registries to RTI. Estimated using the SEER incidence rate of 2.5 cases of osteosarcoma per million persons per year (National Cancer Institute [NCI], 2013) applied to Annual Estimates of the Resident Population by Single-Year of Age and Sex for States from 2003 to 2014 (US Census Bureau, 2016). 9

10 SIR for the Osteosarcoma Surveillance Study as of March 31, 2017 O = 2: Observed number of osteosarcoma cases for diagnosis years with confirmed previous exposure to Forteo E = 3.38: Expected number of osteosarcoma cases exposed to Forteo 10

11 Demographic Characteristics of Interviewed Osteosarcoma Patients as of March 31, 2017 Age Distribution (n = 1,046) Race Distribution 30% 25% 23% 26% 25% 10% 3% 3% Interviewed patients (%) 20% 15% 10% 5% 0% 16% 10% Age distribution (years) 84% Mean age (range): 61 (40-94) years Ethnicity: 5% Hispanic Sex: 52% male Vital status: 22% deceased at the time the case was identified Most common histology codes: 9180: osteosarcoma, NOS (70%) 9181: chondroblastic osteosarcoma (13%) White Black Other Unknown NOS = not otherwise specified. 11

12 Primary Tumor Sites Among Interviewed Osteosarcoma Patients as of March 31,

13 Conclusions The study has identified 2 patients with treatment of teriparatide prior to a diagnosis of osteosarcoma; 3 would have been expected at this point in the study The current SIR is 0.59 (90% CI, ), which is consistent with no increased risk among teriparatide users The two most common histology codes are 9180: osteosarcoma, NOS and 9181: chondroblastic osteosarcoma The three most common primary tumor sites are the leg bones, skull, and pelvis Patient contact studies using state cancer registry data have been demonstrated to be important for ongoing drug safety surveillance For studies investigating rare cancers and/or uncommon drug exposures, participation from a large number of registries is essential 13

14 Thank You! David Harris, MPH