Long-Term Outcomes in Patients with Recurrent Ovarian Cancer and Exceptional Response to PARP Inhibitors
When PARP inhibitor therapy was first introduced, it was supposed to be maintenance treatment aimed at slowing the progression of ovarian cancer. The measure of success was held to be progression-free survival; cure was not expected with most, if not all, patients with ovarian cancer dying from the disease.
It soon became clear that there was a subgroup of patients whose survival was prolonged beyond the 5-year “cure” marker. This was noted in all the clinical trials with up to 20% of participants in the SOLO2 still alive 5 years later.
This retrospective study was of 320 patients who were part of this group, with a history of exceptional survival. About two-thirds of them had received continual treatment with PARP inhibitors; the others had discontinued the drug either due to carer intervention or due to adverse effects or personal preference. The median treatment course was 75 months; the 10-year progression-free survival was almost 80%.
Survival after cancer for this period may be deemed as a cure. It is of note that those exceptional survivors who terminated the treatment early had no worse outcomes. Why this group is exceptional remains unclear, previous work has suggested that a particular location of the DNA mutation of the BRCA gene may be protective. There was no difference between BRCA1 and 2 germline mutations. No increase in marrow dysfunction or myeloid leukaemia is noted with the incidence being small at less than 2%. For some patients, PARP inhibition may be curative. Interruption of treatment does not appear to be harmful.
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