SOLO-1 Paves Path for Frontline Maintenance in Ovarian Cancer

Hye Sook Chon, MD

The phase III SOLO-1 trial led to olaparib (Lynparza) becoming the first PARP inhibitor to receive regulatory approval as frontline maintenance treatment in ovarian cancer, marking one of the key advances within this paradigm over the last decade, explained Hye Sook Chon, MD.

In the study, olaparib induced an unprecedented improvement in progression-free survival (PFS) as frontline maintenance therapy in patients with BRCA-positive advanced ovarian cancer who achieved a partial or complete response (CR) to platinum-based chemotherapy. Results showed that there was 70% reduced risk of disease progression or death in the olaparib arm compared with those who received placebo (HR, 0.30; 95% CI, 0.23-0.41; P <.001).

“This is very exciting time for frontline maintenance treatment in ovarian cancer. In the history ovarian cancer treatment, not much was happening until 2011 when the data achieved by GOG-218 came along,” said Chon, a gynecologic oncologist at Moffitt Cancer Center. “Additionally, the SOLO-1 trial brought very exciting news for all of physicians, patients, and their families. We are very excited for these great data. There are still ongoing clinical trials examining robust treatment options to expand the options for frontline maintenance therapy in advanced ovarian cancer. “

In an interview during the 2019 OncLive^® State of the Science Summit™ on Ovarian Cancer, Chon discussed the progress of maintenance therapy in ovarian cancer.

OncLive: Could you expand on the data that have come out regarding maintenance therapy in ovarian cancer? How do you apply the findings to your own practice?

Chon: The GOG-218 trial examined bevacizumab (Avastin) maintenance treatment and the SOLO-1 trial [examined maintenance olaparib]. If the patient has BRCA mutation, then I start a PARP inhibitor as their maintenance treatment after frontline therapy has been completed. Depending on the surgery information in stage IV disease or chemotherapy before stage III disease, I use bevacizumab.

In the GOG-218 and ICON7 trials, bevacizumab is used as maintenance treatment in patients with ovarian cancer who have a CR or partial response (PR) after they finish chemotherapy. The use of bevacizumab is a little bit different between the trials, but they both show improvement in PFS. That is the main takeaway from those studies.

SOLO-1 is a phase III clinical trial looking at the efficacy of olaparib maintenance treatment in patients who have a BRCA mutation who completed their platinum-based chemotherapy with a CR or PR. Patients were randomized to a placebo or olaparib for up to 2 years depending on their response. The PFS results are very strong; we have never seen [these types of data] before in terms of hazard ratio. Olaparib got the approval [in this setting] from the FDA [based on these data].

What challenges are still faced in the maintenance setting?

We've never had these options before. They came to us in the last decade, which is very exciting. However, we have to think about cost-effectiveness, toxicities, and quality of life (QoL). Patients have been dealing with very difficult times in their lives with surgery and chemotherapy, and considering maintenance treatment when they think they are done [with treatment] is not easy.

How do you discuss the importance of QoL with your patients?

As long as patients tolerate their chemotherapy relatively well, it’s best to start that conversation earlier rather than later. Patients expect to finish and be done following chemotherapy, but many of them may benefit from maintenance therapy. During their chemotherapy, I discuss maintenance therapy to make sure they know what I'm thinking about it. That way, when the time comes, they are not shocked.

What are some ongoing trials in maintenance therapy for ovarian cancer?

Mainly, trials are currently looking at PARP inhibitors using the SOLO-1 trial results; the data are not mature yet. Current trials look at using PARP inhibitors in a different setting than the SOLO-1 trial. The SOLO-1 trial examined BRCA-mutated patients, but current trials include both BRCA-mutated and non¬—BRCA-mutated patients, depending on their age or condition.

Another trial looks at the combination of a PARP inhibitor and bevacizumab as a maintenance regimen. There are also other studies using immunotherapy in combination with PARP inhibitors as a maintenance treatment.

All of the PARP inhibitors are not equal. They have different adverse event profiles and efficacies. I will individualize which one I will choose; I am still waiting on data for more options for our patients.

What is your take home message for others working in this space?

I'm very excited about frontline maintenance for ovarian cancer. We need to educate ourselves and patients so they can prepare to receive maintenance therapy after chemotherapy is done. We'll have more data to come in the next few years. This is a very great time for all of us.

Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379:2495-2505. doi: 10.1056/NEJMoa1810858