Osteosarcoma and Teriparatide?

JOURNAL OF BONE AND MINERAL RESEARCH Volume 22, Number 2, 2007 Published online on November 13, 2006; doi: 10.1359/JBMR.061111 © 2007 American Society for Bone and Mineral Research

Letter to the Editor Osteosarcoma and Teriparatide? To the Editor: We wish to update the medical literature regarding statements that there have been no reports of osteosarcoma in any patients treated with Forteo (Forsteo in Europe).(1,2) Forteo is the trade name for teriparatide [rhPTH(1-34)] 20 ␮g/day, and its labeling includes warnings concerning carcinogenicity assessments showing teriparatide caused osteosarcoma in rats in a manner dependent on both dose and duration of treatment.(2–5) Since first commercial launch in December 2002, Lilly has maintained a worldwide teriparatide 20 ␮g/day safety monitoring program and has recently identified one confirmed case of osteosarcoma in a patient treated with Forteo. A physician communicated the initial report of the case to a Lilly sales representative. The patient was a postmenopausal woman in her 70s with a complex past medical history. The history included osteoporosis with vertebral fractures, and she was treated with Forteo in a manner consistent with the label. Sometime after beginning her second year of Forteo therapy, she was found to have metastatic cancer. She subsequently died, and no autopsy was performed. The primary cancer site was never identified. The initial clinical impression was lung cancer with metastases. The case was referred to a pathology consultant, whose differential diagnosis included several tumor types, including an osteosarcoma variant. Lilly submitted the biopsy materials to another bone pathology expert who communicated on June 29, 2006 that he concluded the lesion was an osteosarcoma. Causality between Forteo and the osteosarcoma in this patient cannot be established, taking into account this was a single case of >250,000 patients in the United States and >300,000 patients worldwide treated with Forteo, the patient had a complex medical history, and the background incidence of osteosarcoma in the general population of men

and women ⱖ60 years of age is 1 in 250,000 per year.(6) The identification of this case does not change the risk/benefit profile for Forteo. Given the known incidence in the general population, very rare cases of osteosarcoma can be expected, irrespective of treatment with Forteo. Lilly will continue to monitor for any signal of increased risk of osteosarcoma in patients treated with Forteo relative to the background incidence.

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REFERENCES 1. Gold DT, Pantos BS, Masica DN, Misurski DA, Marcus R 2006 Initial experience with teriparatide in the United States. Curr Med Res Opin 22:703–708. 2. Tashjian AH Jr, Gagel RF 2006 Teriparatide [human PTH(1-34)]: 2.5 years of experience on the use and safety of the drug for the treatment of osteoporosis. J Bone Miner Res 21:354–365. 3. Vahle JL, Sato M, Long GG, Young JK, Francis PC, Engelhardt JA, Westmore M, Ma L, Nold JB 2002 Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone(1-34) for 2 years and relevance to human safety. Toxicol Pathol 30:312–321. 4. Vahle JL, Long GG, Sandusky G, Westmore M, Ma YL, Sato M 2004 Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose. Toxicol Pathol 32:426–438. 5. Tashjian AH Jr, Chabner BA 2002 Commentary on clinical safety of recombinant human parathyroid hormone 1-34 in the treatment of osteoporosis in men and postmenopausal women. J Bone Miner Res 17:1151–1161. 6. Surveillance Research Program National Cancer Institute SEER*Stat Software, version 6.1.4. Available at www.seer. cancer.gov/seerstat.

Kristine D Harper, John H Krege, Robert Marcus, and Bruce H Mitlak Lilly Research Labs Eli Lilly and Company Indianapolis, IN, USA