Combining PARP inhibition and immune checkpoint blockade in ovarian cancer patients: a new perspective on the horizon?
Lucia Musacchio, Carlo María Cicala, Floriana Camarda, Viola Ghizzoni, Elena Giudice, Maria Vittoria Carbone, Caterina Ricci, Maria Teresa Perri, Francesca Tronconi, Marica Gentile, Vanda Salutari, Giovanni Scambia, Domenica Lorusso
Abstract
•Preclinical data indicate that PARPis exhibit immune modulating properties.•The combination of PARPi with ICIs displays significant synergistic activity in preclinical models.•Phase I and II clinical trials showed encouraging results for this combination, especially in platinum-resistant OC.•Four ongoing phase III trials exploring the combination in first-line setting will delineate the role of immunotherapy in OC. Immune checkpoint inhibitors (ICIs) have completely reshaped the treatment of many malignancies, with remarkable improvements in survival outcomes. In ovarian cancer (OC), however, this emerging class of drugs has not yet found a favorable use due to results from phase I and II studies, which have not suggested a substantial antitumoral activity of these agents when administered as monotherapy. Robust preclinical data seem to suggest that the combination ICIs with poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) may result in a synergistic activity; furthermore, data from phase II clinical studies, evaluating this combination, have shown encouraging outcomes especially for those OC patients not suitable for platinum retreatment. While waiting for ongoing phase III clinical trial results, which will clarify the role of ICIs in combination with PARPis in the newly diagnosed OC, this review aims to summarize the preclinical data and clinical evidence available to date. Immune checkpoint inhibitors (ICIs) have completely reshaped the treatment of many malignancies, with remarkable improvements in survival outcomes. In ovarian cancer (OC), however, this emerging class of drugs has not yet found a favorable use due to results from phase I and II studies, which have not suggested a substantial antitumoral activity of these agents when administered as monotherapy. Robust preclinical data seem to suggest that the combination ICIs with poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) may result in a synergistic activity; furthermore, data from phase II clinical studies, evaluating this combination, have shown encouraging outcomes especially for those OC patients not suitable for platinum retreatment. While waiting for ongoing phase III clinical trial results, which will clarify the role of ICIs in combination with PARPis in the newly diagnosed OC, this review aims to summarize the preclinical data and clinical evidence available to date.