Role of Molecular Testing in Ovarian Cancer
An expert in ovarian cancer discusses the role of molecular testing in ovarian cancer and the benefits of incorporating systemic frontline therapy into treatment plans.
Erin Crane, MD: When discussing molecular testing in ovarian cancer, it is important to remember that there is a difference between somatic and germline testing. The NCCN [National Comprehensive Cancer Network] guidelines, for several years now, have suggested that across the board, all patients should undergo germline testing. About 20% of patients with a particular subtype of high-grade serous epithelial carcinomas will have a hereditary breast and ovarian cancer syndrome such as a BRCA1 or BRCA2 mutation. Somatic testing, or tumor testing, has revolutionized [treatment] over the past couple of years, evidenced by the results that we now have from the SOLO-1 trial, which not only looked at using olaparib in patients with BRCA germline mutations, but also somatic mutations.
There was a significant benefit in progression-free survival for patients with both germline and somatic BRCA mutations, so that shifted our practice toward recommending somatic testing of tumors up front. Then of course, the PRIMA trial came out, and it incorporated niraparib maintenance after frontline treatment in all-comers, regardless of homologous recombination deficiency status. This study found that not only did patients with somatic BRCA or germline BRCA mutations have substantial benefit in progression-free survival with incorporation of PARP maintenance, but so did patients with homologous recombination deficiency.
I would say yes, somatic testing should definitely be incorporated into the standard treatment for all patients at the time of diagnosis. That is something that we do in our practice [at Levine Cancer Institute]. The other way in which it is helpful is that it can help us plan for the future. If you have an unexpected finding, like a high tumor mutational burden, or you are treating someone who has high microsatellite instability, that may be a patient who, down the line, you want to incorporate into immunotherapy. Or they could be randomized to one of the basket or umbrella trials based on their somatic testing results.
In the treatment of frontline ovarian cancer, we use surgery and chemotherapy. Essentially, all chemotherapy regimens include carboplatin. Most of the time, it is combined with paclitaxel,
unless you have a good reason, for example, preexisting neuropathy, to not prescribe this. The majority of patients—80%—will achieve complete remission. Unfortunately, we know that an even higher percentage, 85% of patients, will recur, typically within the first 2 years of treatment. It is very important for us to find ways to extend that initial period of progression-free survival; hopefully, we can even cure patients and extend overall survival. That is what PARP inhibitors have afforded us the ability to do.
The decision to add frontline therapy depends on somatic testing. Of course, for patients with BRCA mutations, the incorporation of olaparib may be suggested due to the results of the SOLO-1 trial, which showed a 56- versus 14-month improvement in disease-free survival in patients with germline or somatic BRCA mutations. In the PRIMA trial, patients who received niraparib who were found to have homologous recombination deficiency benefited and had, essentially, a 22- versus 10-month progression-free survival benefit. We are now incorporating maintenance therapy into the frontline setting, whereas before we had limited options.
There is still, of course, bevacizumab, which we use in the frontline setting. The GOG-0218 trial looked at bevacizumab plus bevacizumab maintenance and found a 3-month improvement in progression-free survival, which many of us may feel is not as clinically meaningful. Many of us may want to reserve bevacizumab for patients in the recurrent setting, or when patients become platinum-resistant. Bevacizumab use is largely a provider choice in a maintenance setting. According to the results of the ICON7 trial, we know that there are some groups who may benefit more from bevacizumab, for example, patients who undergo suboptimal cytoreduction, are diagnosed with stage IV disease, or are have issues with recurrent ascites or pleural effusion.
This transcript was edited for clarity.
Case: A 63-Year-Old Woman With Recurrent Ovarian Cancer
Initial Presentation
- A 63-year-old female presented with early satiety and abdominal discomfort
- PMH: unremarkable, postmenopausal; no known family history of cancer
- PE: left lower quadrant tenderness on palpation
- ECOG PS 1
Clinical work-up
- Pelvic exam with transvaginal ultrasound showed a left ovarian mass
- Transvaginal U/S showed a left ovarian mass
- Chest/abdomen/pelvis CT with contrast confirmed a left adnexal 4.4-cm mass with paraaortic lymph node involvement and ascites
- Paracentesis (1000 cc) cytology confirmed high-grade epithelial ovarian cancer
- Germline molecular testing: HRD+, BRCA1/2-
- CA-125, 370 U/mL
- Diagnosis: Stage III, high-grade epithelial ovarian cancer
Treatment
- Patient underwent TAH/BSO, lymph node dissection, with optimal debulking; R0
- Paclitaxel/carboplatin q3 weeks for 6 cycles; CA-125 decreased; PR
- At 7-month post treatment follow-up imaging showed progression of disease
- Paclitaxel/carboplatin + bevacizumab was initiated q3 weeks for 6 cycles
- At 14-months CA-125 had increased
- Cisplatin/gemcitabine was initiated, PR
- Initiated niraparib maintenance
