CTNI-63. A STUDY OF NIRAPARIB COMBINED WITH RADIOTHERAPY IN PATIENTS WITH RECURRENT GLIOBLASTOMA

Abstract

Abstract BACKGROUND There is no standard therapy for recurrent glioblastoma (rGBM), which has a poor survival, from 3 to 10 months. Radiotherapy is an available option for patients with rGBM, and it could invoke DNA damage, thus leading to tumor cell death. Niraparib is a poly(ADP-ribose) polymerase inhibitor. Preclinical data showed that Niraparib enhances the radiosensitivity of glioblastoma cells. Thus we hypothesize that radiotherapy synergizes with Niraparib to improve the clinical efficacy of anti-tumor.Method:We conducted a phase 2 study combining Niraparib, radiotherapy, and maintenance Niraparib in 30 patients with rGBM. Niraparib(300mg QD) was started at cycle 1 of radiotherapy (55Gy total) and continued until progression or unacceptable toxicity The primary endpoint was 6 month PFS. Secondary endpoints included toxicity, QoL, and OS Result：As of 4/31/2022, 14 patients with a median age of 47 years old (range 26-69) were enrolled. 64.29% were female. Eight patients（57.1%）had experienced ≥ 2 previous therapy（range 1-4）. The MGMT methylation status was available for 12 patients, and 9（64.3%）had unmethylated MGMT. The median follow-up was 167 days (95%CI 124-263). PFS 6 was 36% (95%CI 12.17%-60.92%), OS 6 was 82.61%(95%CI 46.51%-95.34%). The mPFS was 157 days (95%CI 93-188), the mOS was not reached (95%CI 188-NA), three patients had an OS of more than 10 months by the data submitted. The ORR was 35.7%, one patient achieved CR,four achieved PR. Niraparib combined radiotherapy showed efficacy in controlling local lesions. At 1 and 3 months, local control rate was 85.7% and 64.3% ,respectively. The most common serious adverse event was thrombocytopenia（28.57%）which could be controlled by adjusting the dosage of Niraparib. CONCLUSION Niraparib combined radiotherapy is well tolerated and shows efficacy in rGBM patients. Survival data will be updated.Clinical registration number: NCT04715620