David O’Malley, MD:The ARIEL3 results were very impressive and very consistent with the other PARP inhibitors when we look at platinum-sensitive recurrence maintenance therapy. We looked at the intent-to-treat population, the BRCA-like population, and the BRCA-positive population. It’s very important to note that they include both somatic and germline mutations in those patients.
When we look at those hazard ratios, starting with the positive BRCAgroup, we’re really looking at a hazard ratio of 0.23 and a significant difference in the medium progression-free survival, obviously, in addition to the hazard ratio. However, when we include all of the patients, the hazard ratio regarding improvement is still 0.3, and with that was obviously a significant impact on these patients. Even in a patient who is not BRCA-like or BRCA-positive, both germline and somatic, it’s a very reasonable option. The decision to treat this patient with PARP inhibitor was actually easier because she had already received bevacizumab. In that instance, when we look at those patients who have received prior bevacizumab, there does not seem to be any difference in their responses from ARIEL3.
One differentiating aspect of rucaparib is the inclusion in ARIEL3 of patients with bulky disease, disease greater than 2 cm. In a preplanned analysis, they actually looked at the outcomes of those patients. Those patients who hadBRCAmutations, both somatic and germline, had an approximately 35% response rate, and half of those were complete responses. In the intent-to-treat population, those patients at a complete response were about 7%, and those patients who had a response were approximately 17%. Approximately 17% to 35% of those patients will get response. The majority of patients did have stable disease.
The package insert for rucaparib will say to dose reduce from 600 mg to 500 mg. The challenge with that is that the patient has 300-mg tabs at home and they take 2 tabs twice a day, so a dose reduction does require another prescription. Often, my first dose reduction until they exhaust the prescription will be to omit 1 of the tabs in the daytimeif it’s fatigue, for example—and have 2 tabs at night. It becomes 600 mg at night and 300 mg during the day. Once they exhaust that prescription and they need a new prescription, we will write for the 300 mg and 200 mg tabs. Because of these medications and the availability of them at home, we do at times modify the dosing, but the package insert clearly says that the first dose reduction should be to 500 mg.
Transcript edited for clarity.
Case: A 69-year-old Woman with Advanced Serous Ovarian Cancer