A phase II of everolimus and octreotide for patients with refractory and documented progressive meningioma (CEVOREM).

Abstract

2011 Background: After iterative surgeries and radiotherapy (RT)/radiosurgery (RS) failure, aggressive meningiomas remain an unmet medical need. We have shown in vitro that everolimus (EVE) combined to octreotide (OCT) is active in meningiomas. Methods: Prospective multicentric single arm phase II study (NCT02333565) including pts with recurrent meningioma with documented progression ( > 10% increase of tumor surface over 6 months) after surgery and RT/RS. EVE was orally administrated at 10mg/day and OCT by IM injection 30 mg/28 days. MRI was performed every 3 months with planned central review of imaging including volumetric progression at inclusion and during treatment. The primary endpoint was PFS6. The criteria for success was defined as a PFS6 > 40%. Results: 20 pts were included, aged 30-75 years (median 55) with 37 progressive intra cranial meningiomas (WHO: 2 grade I, 27 grade II, 8 grade III) including 4 NF2 pts. Median KPS was 70%. All pts previously underwent at least one surgery and more than 1 in 18/20 patients. 19/20 pts were treated with radiotherapy or radiosurgery and 5 pts with prior chemotherapy. 1 pt was not evaluable at 3 months. With a median f/u of 12.3 months (2-24 months), PFS6 was 58.2% (95% CI 33.5-76.5%) and PFS12 was 38% (95% CI 16-60%). Volumetric analysis at 3 months demonstrated a decrease in tumor volume superior to 10% in 8 tumors (4 pts). Pre therapeutic growth rate was decreased of more than 50% in 29/35 tumors (18/20 pts) during the first 3 months. Inclusion (I)-to-3 months tumor growth rate (mean at 1.9%/month) was significantly lower than pre inclusion (Pre-I)-to-I growth rate (mean at 18.5%/month) (p = 0.0003). 3 highly aggressive tumors (3 pts) were separately assessed: Pre-I-to-I growth rate superior to 1000%/month was decreased to 3%, 15% and 44%/month in the first 3 months. Toxicity included 7 grade III AE (stomatitis, 3; pneumopathy, 1). AE of special interest included stomatitis (10, 50%), rash (8, 40%), abdominal pain and diarrhea (11, 55%) and nausea and vomiting (4, 20%). Conclusions: Everolimus and octreotide combination appears active in refractory aggressive and progressive meningiomas with acceptable and manageable toxicity and should request further evaluation. Clinical trial information: NCT02333565.