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Alastair Thomson,1 Lucinda Gunn,1 Deborah Victor,1 Ellis Adamson,1 Kashyap Thakrar2 1Oncology Department, Sunrise Centre, Royal Cornwall Hospital, Truro, Cornwall, UK; 2Accord-UK Ltd, Barnstaple, Devon, UKCorrespondence: Alastair Thomson, Oncology department, Sunrise Centre, Royal Cornwall Hospital, Truro, Cornwall, TR1 3LJ, UK, Tel +44 (0)1872 250000, Email alastairthomson1@nhs.netBackground: In the UK, relugolix, an oral gonadotropin-releasing hormone receptor antagonist, is indicated for advanced hormone-sensitive prostate cancer, and as neo-adjuvant and adjuvant treatment in combination with radiotherapy in patients with high-risk localised or locally advanced hormone-dependent prostate cancer. Experience with the combination of oral relugolix plus oral enzalutamide is limited.Case Presentation: A white British male (66 years old) with a history of myelodysplastic syndrome, chronic neutropenia and indeterminate colitis presented with metastatic adenocarcinoma of the prostate gland. The patient started subcutaneous leuprorelin acetate and oral enzalutamide. After 8 weeks, the oral enzalutamide dose was reduced because of fatigue. Following the second leuprorelin injection, the patient developed a subcutaneous abscess that required surgical incision and drainage. The patient switched to oral relugolix and continued with oral enzalutamide. Within 3 months of commencing leuprorelin and enzalutamide the prostate specific antigen (PSA) concentration fell from a peak of 269.00 ng/mL to 2.55 ng/mL. Following the switch to oral relugolix plus enzalutamide, the PSA remained stable until the most recent assessment 11 months later. Relugolix plus enzalutamide was well tolerated.Conclusion: Relugolix plus enzalutamide produced a sustained reduction in PSA and the combination was well tolerated. Further research including real world data should assess relugolix in doublet and triplet combinations for prostate cancer.Plain Language Summary: Oral (by mouth) relugolix can treat certain men with hormone sensitive prostate cancer. Studies are underway looking at relugolix combined with other drugs, such as oral enzalutamide, and at various stages of prostate cancer. Dr Thomson et al report the case of a man with other serious diseases who took oral relugolix and oral enzalutamide after experiencing side effects with injectable drugs. His levels of prostate specific antigen (PSA), which indicates prostate cancer control (the lower the better), fell markedly after starting treatment and, after switching to relugolix, remained stable for 11 months. He tolerated relugolix plus enzalutamide well.Keywords: relugolix, enzalutamide, prostate cancer, gonadotropin-releasing hormone receptor antagonist, prostate specific antigen