Combination therapies with olaparib — new treatment options

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Introduction. Olaparib, the first approved poly(ADP)-ribose polymerase (PARP) inhibitor (PARPi), is a cornerstone of targeted therapy in patients with homologous recombination deficiency (HRD), in particular with pathogenic (P) or likely pathogenic (LP) variants in the BRCA1/2 genes. Growing evidence also indicates its efficacy in combination therapies, regardless of the presence of classical HRD markers. Material and methods. A narrative literature review was conducted, including the results of clinical trials with olaparib in monotherapy and combination therapies, preclinical data, current guidelines of scientific societies (ESMO, NCCN, PTOK, PTGO) and the role of molecular diagnostics, including the presence of P/LP variants, both germline and somatic, in the qualification for therapy in ovarian, endometrial and prostate cancer. Results. Combination therapy with olaparib and bevacizumab shows high efficacy in patients with ovarian cancer and HRD. The DUO-E study confirmed the clinical benefit of olaparib in combination with durvalumab in patients with endometrial cancer and proficient mismatch repair (pMMR), usually poorly responding to immunotherapy. Olaparib also shows efficacy in patients with prostate cancer and P/LP variants in BRCA1/2 genes, both as monotherapy and in combination with new hormonal agents, regardless of HRD status. Conclusions. Olaparib in monotherapy is effective in patients with P/LP variants in the BRCA1/2 genes, while its use in combination therapies allows for the extension of indications for targeted treatment. Comprehensive molecular diagnostics and further research on the mechanisms of resistance and new strategies for personalizing oncological treatment are of key importance.

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