Genomic Profiling in ctDNA Revealing Complicated Resistance Mechanism of Olaparib and Abiraterone as Salvage Therapy in Prostate Cancer: A Case Report

Abstract Background: PARP inhibitor, e.g. Olaparib, displayed superior clinical effect in metastatic castration prostate cancer (mCRPC) patients with deleterious mutations of DNA damage repair genes (DDR) as reported recently. Besides, for mCRPC patients without DDR alterations, a combination of Olaparib and abiraterone may achieve an acceptable clinical outcome as indicated by researches. However, these previous clinical studies involved patients strictly following inclusion criteria. In real-world situations, where the situation of patients is more complicated, the efficacy of salvage treatment of Olaparib with or without abiraterone-prednisone remains to be unclear. Case presentation: The present case displayed a 61-year-old man who was initially diagnosed with metastatic hormone-sensitive prostate cancer(mHSPC) and proceeding into mCRPC after several kinds of standard therapies. Surprisingly, the patient had a well TPSA response and remission of symptoms for four months by taking Olaparib combined with abiraterone-prednisone, basing on androgen-deprivation therapy (ADT). The resistance of Olaparib was occurred with slowly increasing serum TPSA level again.Conclusion: Resistance mechanism as discovered by comprehensive genomics profiling. The major concern was that two somatic reversion mutations occurred in PALB2 recovering its reading framer storing the function of the primary PALB2 mutation and caused the resistance to a PARP inhibitor.