First-Line PARPi Maintenance in Advanced Ovarian Cancer - Episode 2
Wendel Naumann, MD:This is a typical case of a patient with ovarian cancer. She’s young. It’s not unexpected that she has aBRCAmutation. Patients withBRCAmutations often respond very well to chemotherapy, and so even if the primary surgery shows gross residual disease, very often a secondary cytoreductive surgery can be performed to get down to no gross residual disease. We certainly think it’s reasonable to switch to IV/IP [intravenous/intraperitoneal] platinum in these patients. If you look at the study GOG-172, those patients, there was some thought that theBRCA-positive patients had a better response to IP therapy than the non-BRCApatients. The subsequent studies have been negative for IP therapy, but I still think there’s a value, especially in patients who haveBRCAmutations, of the IP route of treatment. And that’s based on some of the data from our institution as well.
The genetic testing that we use for patients with ovarian cancer is generally a panel-based test where we test a wide variety of different things. We also look at the MMR [mismatch repair] proteins and look for Lynch syndrome, as well as theBRCAand theBRCA-like proteins, things likeRAD51Cand some of the otherBRCA-pathway genes.
The prognosis for ovarian cancer is generally good, particularly in the short term. I think with theBRCAmutations, the prognosis can be better. I think one of the things that we learned from the SOLO-1 study is that the prognosis forBRCApatients treated with IV chemotherapy alone was not as good as we thought. In that study, patients had a median time to recurrence of only about 13 to 14 months after being treated with IV chemotherapy and no maintenance therapy. So, I think the idea that patients, even though they respond better withBRCAmutations, the idea that they do better may not actually be true. Now they may respond better to further therapy. But when we look at maintenance therapy in that patient population, they do extremely well. When you look back at the SOLO-1 study, patients who received PARP [poly ADP ribose polymerase] inhibitor as maintenance therapy, they had greater than 50% progression-free survival at 4 years.
The prognosis for patients with residual disease after surgery is varied, depending on how well they respond to chemotherapy. Obviously, we want to get patients down to no visible residual disease. That’s our goal with surgery, but that’s not always possible. And the other thing we’ve learned about surgery is, the more intense the surgery is, the more invasive the surgery is, generally the less well they do, even if we get them down to no residual disease. And I think that speaks to the biology of the cancer. So in patients who require extensive upper abdominal resection, their prognosis even at no residual disease is not as good as patients who are more easily debulked. And so, I think this is a surrogate marker for prognosis, as well as effect of the surgery.
When we see patients with ovarian cancer, we must decide whether we’re going to do primary surgery or are we going to do neoadjuvant chemotherapy. My approach is that we generally do neoadjuvant chemotherapy for people who present with ascites. Anybody who we think that is not going to be completely resected at the time of surgery, I would favor a neoadjuvant approach and then come back with surgery after 3 cycles of chemotherapy. We know that that approach leads to a higher R0 resection rate. It probably lessens the morbidity of surgery.
We have 4 clinical trials that have shown that patients treated with neoadjuvant chemotherapy do just as well as patients treated with upfront surgery. I think if we can lessen the morbidity of surgery, that’s really a good thing. Many times we can even go back, and particularly for theBRCA-positive patients, about a quarter of these patients will have no residual disease after 3 cycles of chemotherapy.
Transcript edited for clarity.
Case: A 54-Year-Old Female With Ovarian Cancer
H & P