Western Regional Blog – BC, YK, AB, NWT and Nunavut
The trial results show successful PARP inhibitor use as maintenance therapy and avoid the toxicity challenge of combinations with cytotoxic chemotherapy.
Importantly, the BRCA mutation is a robust biomarker for benefit and will be appropriately used to guide phase III studies for this indication. However, this biomarker should not limit all future investigations with PARP. BRCA deficiency is a fraction of the causes of defective DNA repair. Other sites of intervention in the pathway, such as ATM (ataxia telangiectasia mutated) kinase, are warranted. In fact, PARP inhibitor activity independent of BRCA status has been shown in breast cancer, for example.
Maintenance PARP inhibition has thus far not improved survival in ovarian cancer. It may just be that we can’t detect an overall survival benefit in our maintenance studies because of the effect of subsequent therapy. A related issue is thus when to use this strategy. The data suggest that there is enhanced or at least preserved activity as you move along the disease course. So the question is, if we have a strategy that confers about a 6-month progression-free survival advantage, yet may not affect overall survival, where in the disease course should that be used? That’s a critical question that remains to be answered.
Dr. Paul Sabbatini is deputy physician-in-chief for clinical research at Memorial Sloan-Kettering Cancer Center in New York. He was the invited discussant for the study at the meeting. Dr. Sabbatini disclosed no relevant conflicts of interest.