UPDATED LONG-TERM SURVIVAL AND SAFETY DATA FROM A PIVOTAL, OPEN-LABEL, MULTI-CENTER PHASE 2 STUDY OF HSA I-131-MIBG IN PHEOCHROMOCYTOMA OR PARAGANGLIOMA PATIENTS WITH UNRESECTABLE, LOCALLY ADVANCED OR METASTATIC DISEASE
Friday, May 8, 2020
11:45 AM – 12:00 PM
Participants should be aware of the following financial/non-financial relationships: Vincent DiPippo, PhD: Disclosure information not submitted.
Objective : There is a high unmet medical need for effective treatment options for patients with advanced pheochromocytoma/paraganglioma (PPGL), rare neuroendocrine tumors with a 5-yr survival rate as low as 12%. AZEDRA®, a high-specific-activity iodine-131 meta-iodobenzylguanidine (HSA I-131-MIBG), is the first and only FDA-approved therapeutic radiopharmaceutical agent indicated for the treatment of adult and pediatric patients with iobenguane scan positive, unresectable, locally advanced or metastatic PPGL who require systemic anticancer therapy. We report updated survival data, new efficacy subanalyses, and safety results.
Methods: Patients with advanced PPGL who were heavily pre-treated and were ineligible for curative surgery or chemotherapy received a dosimetric dose followed by up to two therapeutic doses (each at 296 MBq/kg to a max of 18.5 GBq). The primary endpoint, defined as the proportion of patients with at least 50% reduction of all antihypertensive medication(s) lasting ≥6 months, was met and previously reported. Updated secondary endpoints including overall survival (OS) and safety are reported.
Results: 74 patients received a dosimetric dose of HSA I-131-MIBG. Of those, 68 patients received one therapeutic dose and 50 received two doses of HSA I-131-MIBG. Clinical benefit rates (objective tumor responses defined by RECIST 1.0 and stable disease) were observed in 71.4% and 98.0% of patients receiving one and two therapeutic doses, respectively. As of October 10, 2019, median survival time for all patients was 43.2 months (95% CI 31.4, >60). Median survival time was 19.3 months (95% CI 4.5, 32.4) and 49.1 months (95% CI 36.9, >60) in patients receiving one and two doses, respectively. The overall survival was 73.8% at 2 yrs, 47.5% at 4 yrs and 41.5% at 5 yrs. The most common (≥50%) adverse events were nausea, fatigue, and myelosuppression. Myelosuppressive events resolved within 4-8 wks without requiring stem cell transplantation. Late radiation toxicity included 7 patients with secondary malignancies (myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), colon cancer, and lung carcinoma) of which MDS, ALL and AML were considered related to I-131 radiotherapy.
Discussion/Conclusion: Results from this pivotal phase 2 study suggest that HSA I-131-MIBG is a safe and efficacious treatment for advanced PPGL.