World Ovarian Cancer Day: Biomarkers Shape Treatment Decisions for Ovarian Cancer

Natalie Godbee, DO

Gynecologic Oncologist, City of Hope Atlanta

Genetic markers are taking on an even greater significance in ovarian cancer, a disease that has long been associated with the role of BRCA1/2 gene mutations in many patients. Testing for particular biomarkers not only predicts risk factors for disease but can also guide treatment choices for patients with advanced ovarian cancer in order to maximize survival outcomes.

Targeted therapy with PARP inhibitors initially showed efficacy in patients with BRCA mutations, but now benefit has been shown for those with BRCA wild-type disease with homologous recombination deficiency (HRD) as well, making testing for both of these biomarkers crucial. Originally approved in later lines of therapy, PARP inhibitor therapy has been shown to be beneficial earlier in treatment, and now plays a role as primary maintenance following frontline platinum-based chemotherapy. Studies have shown that these therapies can double the duration of progression-free survival (PFS).^1,2

Other targeted treatment approaches are on the horizon, with mirvetuximab soravtansine-gynx (Elahere)—an antibody and microtubule inhibitor conjugate—receiving accelerated approval for patients with platinum-resistant epithelial ovarian cancer with high expression of folate receptor alpha.³ Because of ovarian cancer’s high rate of recurrence, genetic testing with next-generation sequencing (NGS) and other tools is a vital way to find clinical trials for patients with recurrent disease.

In an interview with Targeted Oncology^TM, Natalie Godbee, DO, a gynecologic oncologist at City of Hope Atlanta, discussed the current state of treatment for advanced ovarian cancer and how oncologists can get the best outcomes for their patients.

Targeted Oncology: Can you discuss how the field has changed compared with a few years ago?

GODBEE: Within the past 10 years, we've had a lot of changes with ovarian cancer. This was when PARP inhibitors were introduced to our community, and they were a change from the traditional chemotherapy. Initially, when they were introduced, we were using them for second-line maintenance as well as treatment in the third and fourth line. However, now we're able to use those as first-line maintenance therapy. We not only look at their BRCA [mutation] status, but at patients’ homologous recombination status now because if they are HRD, they will respond to these PARP inhibitors.

What are some trials that you feel have been most practice changing?

The latest trials that have made most impact for us would be the PRIMA trial [NCT02655016] and PAOLA-1 trial [NCT02477644]. These involve the PARP inhibitors being used as first-line maintenance. The maintenance idea was introduced several years ago with chemotherapy first and we found that it worked well. Then when we introduced the VEGF inhibitor bevacizumab (Avastin), it was used as maintenance and were shown to have a good benefit prolonging the PFS.⁴ Using the PARP inhibitors as second line, we saw that patients had a longer PFS. Thus, we investigated them in the first-line setting.

PRIMA looked at using niraparib (Zejula) versus placebo in newly diagnosed patients who had a response to platinum agents. The median PFS was significantly better on niraparib compared with placebo, and that was 13 months for niraparib versus 8 months with placebo.¹ This was regardless of their HRD status or BRCA status. PAOLA-1 looked at using bevacizumab [Avastin] maintenance with placebo and compared it with bevacizumab and olaparib [Lynparza] in newly diagnosed ovarian cancer patients who responded to platinum based chemotherapy. We saw a great benefit using the PARP inhibitor plus bevacizumab as a maintenance therapy. The PFS was shown to be higher for patients who were HRD positive and BRCA positive.² For our patients with newly diagnosed ovarian cancer, we are checking not only BRCA status but HRD status to help guide us to the appropriate maintenance therapy.

How do you usually sequence therapies depending on whether they have BRCA status or not?

When a patient is initially diagnosed, the BRCA and homologous recombination status will be checked. Then if they are a candidate for bevacizumab, they'll receive that with the upfront adjuvant therapy. Once we get the BRCA and HRD testing back, we can use this information to determine if the patient is a candidate for niraparib or olaparib maintenance therapy.

Are there any other targets and trials that you feel are relevant in the space?

Last year we got approval for mirvetuximab soravtansine-gynx, an antibody for an alpha folate receptor. The SORAYA trial [NCT04296890] looked at patients who were platinum resistant and previously treated with 1 to 3 lines of therapy. These patients are usually a challenge to treat. The antibody therapy mirvetuximab showed an objective response rate of 31.7%, which was better than what we were seeing with any of the other chemotherapies for these platinum-resistant patients, so it gained accelerated FDA approval.^3,5 That's newer on the market for our patients.

What do you think is some advice that would be good for any community oncologists who don't usually treat ovarian cancer

Ovarian cancer is very challenging; we know that 75% of [patients] will present with late-stage disease, and we know that 75% to 80% of them will recur. It becomes a challenge when they do recur, and we want to find the best treatments for them. I encourage oncologists to check genomic testing with NGS, because these tests are opening treatment options for patients.

We always encourage for recurrent patients and even for those in the first-line setting, to look for clinical trials because this is where they're going to receive immune checkpoint inhibitors [or] targeted therapies. This is where patients are receiving the benefit. Clinical trials are always a plus for patients.

Is there anything that you would like to highlight in this setting?

I want to emphasize NGS molecular testing. We do it rather frequently at City of Hope [Atlanta]. I personally have had patients who qualify for clinical trials based on it, and we found some treatments [that] have good responses. One particular patient with ovarian cancer became platinum resistant and we [found a] treatment based off of that molecular testing, and 3 years later she's still doing very well. It's important to do the testing to give patients additional options aside from traditional chemotherapy.

_References:

_{1. González-Martín A, Pothuri B, Vergote I, et al; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019:381(25):2391-2402. doi:10.1056/NEJMoa1910962}

_{2. Ray-Coquard I, Pautier P, Pignata S, et al; PAOLA-1 Investigators. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381(25):2416-2428. doi:10.1056/NEJMoa1911361}

_{3. FDA grants accelerated approval to mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or peritoneal cancer. News release. FDA. November 14, 2022. Accessed April 28, 2023. https://bit.ly/3oUykl8}

_{4. Burger RA, Brady MF, Bookman MA, et al. Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer. N Engl J Med. 2011;365(26):2473-2483. doi: 10.1056/NEJMoa1104390}

_{5. Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. J Clin Oncol. 2023;41(13):2436-2445). doi:10.1200/JCO.22.01900}