Expanding Role of PARP Inhibitors in Advanced Ovarian Cancer - Episode 6
Michael Birrer, MD: The upfront treatment of ovarian cancer has also undergone an important evolution, and now we have choices. We should first talk about the specific histologies of ovarian cancer. We know that clear-cell and endometrioid and papillary serous tumors are different, but the truth is, we’re not to the point where we would actually treat them with different upfront treatments or therapies. The 1 exception, I think, is potentially mucinous tumors, which are rare, and most of us think they probably behave like GI [gastrointestinal] cancers. Although I use carboplatin and Taxol [paclitaxel], some individuals might use a GI regimen.
For the tumors that I related to before—papillary serous, endometrioid, and clear cell—the standard upfront therapy would be carboplatin and Taxol on an every-3-weeks basis. This is the historic traditional therapy. I’m an old guy, so I like old therapies; that’s what I use. There was a JGOG [Japanese Gynecologic Oncology Group] study, a Japanese GOG study, that used a dosage-dense approach that suggested it was not only effective but provided a survival advantage to patients.
The ICON8 trial, which was a very well-designed trial, tested that regimen compared with every 3 weeks and found no difference. So I do think that dosage-dense Taxol—that’s 80 mg/m2 weekly of the Taxol—is an acceptable regimen. There’s no real evidence in my mind that it’s superior than every 3 weeks.
And then one cannot get through this discussion without at least mentioning intraperitoneal [IP] therapy. Intraperitoneal therapy is when the chemotherapy is put directly into the peritoneal cavity. It has also undergone an evolution, with recent studies showing no survival advantage over IV [intravenous], but there are still physicians, mostly gynecologic oncologists, who utilize IP therapy for this patient population. Then let me finish by saying what the new discoveries have been. And that would be the addition of bevacizumab to this regimen. The testing of bevacizumab in combination with chemotherapy and in maintenance for upfront therapy of patients with ovarian cancer was tested in GOG 2018 and ICON7 literally 10 years ago.
The use of it was approved in Europe for upfront therapies, but only in the last 6 months has it been approved in the United States. But we now do have approval, and bevacizumab is perfectly reasonable. I’m using it in the majority of my patients. The drug is given on a 3-week basis concurrently and then, according to the GOG 2018 data, it is given for 15 months, or 22 cycles.
Ursula A. Matulonis, MD: After patients are diagnosed and undergo treatment—and that treatment is typically carboplatin and paclitaxel, that is standard of care across the world—some patients may also be eligible for bevacizumab. And that’s been FDA approved in the United States for patients with advanced stage III or stage IV cancer who have residual cancer behind. It’s also approved in Europe and other parts of the world. And now olaparib has been approved for patients who have advanced disease and have an underlying BRCA mutation, either somatic mutation or a germline mutation. Once patients complete their 6 cycles of carboplatin-paclitaxel, some women could go on to continue maintenance therapy. If they started with bevacizumab as part of their upfront regimen, that bevacizumab continues up for 22 cycles additionally.
If patients are found to have a deleterious BRCA mutation, either germline or somatic, they’re eligible to receive olaparib because of the very impressive SOLO-1 results. And once patients finish their chemotherapy, regardless if they’re on maintenance therapy or not on maintenance therapy, we typically follow folks every 3 months for the first 2 years. And that visit may include a physical exam, a CA 125 [cancer antigen 125] test. Most of us do not do routine imaging, so we do not do routine CTs [computed tomography] or PETs [positron emission tomography scans], but we really follow patients’ CA-125 values, especially if those CA-125 values were elevated at initial diagnosis. The times when I’ve done more routine radiographic imaging are in patients who do not have an elevated CA-125 to start with, so you can’t really use that as a reliable measure.
So we follow women for the first 2 years after they’ve completed chemotherapy with the CA 125 test to detect any changes or in other words, elevations of that number. And unfortunately, most of our patients will have a recurrence of their cancer. Initially, the ovarian cancer—specifically, really high-grade serous ovarian cancer, but also other high-grade tumors—are very sensitive to chemotherapy. But then typically within about a year to a year and a half, patients will begin to have a rise in their CA-125, indicating that there’s cancer that started to grow again.
For newly diagnosed patients, there’s a lot to discuss during those early visits. It’s important to understand the pathology, so we’ve talked about the importance of high-grade serous ovarian cancer. We’ve talked about maintenance strategies, specifically bevacizumab maintenance strategy, olaparib maintenance strategy postchemotherapy. And then something important for oncologists to remember is for patients who have low-grade serous carcinomas, which is a rarer type that occurs in younger women, and for those patients who have more advanced disease, the recommendation has now been to start hormonal therapy as a maintenance therapy. And that’s in the NCCN [National Comprehensive Cancer Network] Guidelines as well.
But certainly, for all our patients, regardless if they’re stage I all the way through stage IV, I will have a discussion about risk of recurrence. But as we know, it’s not always perfect. And the exciting part is that a lot of our therapies are quite effective in delaying progression, maintenance therapies like aromatase inhibitors for low-grade serous carcinoma. Bevacizumab for appropriate patients can delay recurrence by about 6 months. And then now certainly the use of olaparib as maintenance therapy shows a 70% reduction in the risk of progression or death for patients who have underlying BRCA mutations. So I explain to patients that we have a lot of new therapies, and we’re becoming more precise in how we prescribe these different therapies.
Transcript Edited for Clarity.