Randomized phase III trial to evaluate radiopharmaceuticals and zoledronic acid in the palliation of osteoblastic metastases from lung, breast, and prostate cancer: Report of RTOG 0517.

Abstract

TPS9150 Background: Skeletal related events (SREs) diminish quality of life (QOL) as well as overall survival (OS) in patients with bone metastases, a common event in breast, lung and prostate cancer. SREs can be reduced or delayed by the use of bisphosphonates. It is postulated that the radiopharmaceuticals, Strontium-89 (Sr89) and Samarium-153 (Sm153), when added to a bisphosphonate can decrease the incidence of SREs. Methods: RTOG 0517 randomized patients with breast, lung and prostate cancer and blastic bone metastases to either Zoledronic acid (ZA) alone or ZA plus a single standard dose of either Sr89 or Sm153. No limitations were placed on additional therapy such as chemotherapy or hormonal treatment. The projected median time to SRE [pathological bone fracture, spinal cord compression, surgery to bone, or radiation to bone] for the ZA arm was 10.4 months requiring 257 SRE events to detect a 33% relative reduction for the radiopharmaceutical arm in the time to development of an SRE with 90% power. Other study objectives included quality of life, pain control, OS and toxicity. Results: 261 patients (median age 68; 62% male; 55% prostate, 35% breast, 10% lung) were accrued from July 2006 through February 2011 (4.6 patients/month). Due to a lower than expected rate of SREs in the control (ZA) arm, the study was closed early and therefore did not reach the targeted accrual. 28 (17.4%) patients in the ZA arm and 27 (16.8%) in the radiopharmaceutical arm experienced an SRE. Median time to development of an SRE in the ZA and radiopharmaceutical arms was 11.60 and 16.74 months, respectively (p=.47). Median OS in the ZA arm and radiopharmaceutical arm was 15.95 and 11.18 months, respectively (p=0.12). Cox proportional hazards regression model showed that baseline characteristics, including gender, race, ethnicity, primary disease site or number of bone metastases, had no significant impact on OS. There was no difference in QOL parameters or toxicities between the two arms. Conclusion: Patients receiving ZA only experienced a much lower SRE rate than was hypothesized. The addition of Sr89 or Sm153 did not result in a difference in SREs, OS, or QOL