Ovarian cancer recurrence: is the definition of platinum resistance modified by PARPi and other intervening treatments? The evolving landscape in the management of platinum-resistant ovarian cancer

Abstract

Definitions of platinum resistance have been questioned and changed over the last five years, even though no predictive biomarker of resistance exists. These have sculpted how we approach platinum retreatment and, consequently, how we devise new treatment strategies for those patients with tumour progression on platinum therapy. Platinum-non-eligible ovarian cancer is treated with single-agent non-platinum drugs. When bevacizumab can be added to chemotherapy, progression-free survival improves significantly. For patients with a BRCA mutation, PARP inhibitor monotherapy is an option compared to chemotherapy. There is currently no clearly identified role for immune-checkpoint inhibition in this patient population. This review describes some of the challenges in treating patients with platinum resistance and suggests refinements in the selection of patients most likely to benefit from targeting a DNA damage response, angiogenesis or immune modulation. It also describes novel agents of interest and possible mechanisms of the synergy of therapeutic combinations.

Keywords

Platinum resistance / PARP inhibitors / VEGF inhibitors / immune checkpoint inhibitors / DNA damage response

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