Mihaela C. Cristea, MD, discusses the impact of the SOLO-1 trial on current approaches to frontline maintenance therapy as well as the trials that are underway with niraparib, rucaparib, and the investigational PARP inhibitor veliparib.
Mihaela C. Cristea, MD
In the phase III SOLO-1 trial, olaparib (Lynparza) resulted in an unprecedented improvement in progression-free survival (PFS) as frontline maintenance therapy in women with BRCA-positive advanced ovarian cancer. With 2 additional PARP inhibitors under investigation, the field is likely to see survival improvements on the same scale in the future by homing in on a wider scope of aberrations, explained Mihaela C. Cristea, MD.
In the trial, patients who achieved a partial or complete response to platinum-based chemotherapy and received olaparib until progression had a 70% reduced risk of disease progression or death compared with patients who received placebo. In December 2018, olaparib became the first PARP inhibitor to receive regulatory approval as frontline maintenance treatment.
Anticipated phase III studies include the PRIMA (NCT02655016), ATHENA (NCT03522246), and PAOLA-1 (NCT02477644) trials in which niraparib (Zejula), rucaparib (Rubraca), and olaparib, respectively are being used alone or in combination with either checkpoint inhibition or antiangiogenic therapy. Though BRCA positivity is an inclusion criterion in the PAOLA-1 trial, PRIMA and ATHENA will assess all-comers according to BRCA status as well as homologous recombination status.
“The goal of ongoing studies is to define other subgroups who may benefit from maintenance, whether based on other molecular targets like homologous recombination deficiency or LDH targets. Whether maintenance can benefit everybody as we have seen in the recurrent setting is to be seen,” said Cristea.
In an interview during the 2019 OncLive® State of the Science Summit™ on Ovarian Cancer, Cristea, an associate clinical professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, discussed the impact of the SOLO-1 trial on current approaches to frontline maintenance therapy as well as the trials that are underway with niraparib, rucaparib, and the investigational PARP inhibitor veliparib.
OncLive: Could you discuss the impact of the SOLO-1 data on frontline maintenance therapy in ovarian cancer?
Cristea: The SOLO-1 trial was a landmark clinical trial, published only 6 months ago. This study has changed the standard of care. There are [several] important lessons from SOLO-1. One is that all patients need to complete molecular testing before finishing adjuvant chemotherapy, so that [appropriate] patients can continue with olaparib. This approach will prolong their remission by an additional 3 years.
Have the other 2 PARP inhibitors shown the same magnitude of benefit?
There are a number of ongoing clinical trials looking at other PARP inhibitors, such as in the PRIMA study with niraparib. That study has not been reported, but we are expecting efficacy data by the end of 2019. The trial is similar to SOLO-1, but is using a different PARP inhibitor. Additionally, the study is not limited to patients with BRCA mutations. There are a number of other studies, including the ATHENA trial with rucaparib. That trial is complex, which is looking at various combinations of PARP inhibitors plus checkpoint inhibitors versus single agents as maintenance therapy.
Could there likely be a repeat of SOLO-1 with the other PARP inhibitors?
We will—the dilemma will be in sequencing these agents. The goal is to cure more patients. The difficulties will be in dealing with recurrent disease after exposure to all of these agents in the frontline setting.
For patients who don't have BRCA1/2 mutations, have there been any advances regarding maintenance therapy?
The only maintenance therapy that can be offered is the antiangiogenic agent bevacizumab (Avastin) in combination with chemotherapy as well as following chemotherapy. At this point, that is the only viable option. An older study utilized maintenance paclitaxel, but it is no longer used in clinical practice.
Are there any other studies clinicians should be aware of?
There are a number of randomized studies, including PRIMA and ATHENA. There is also the PAOLA-1 study with olaparib. Additionally, there is a study looking at veliparib, which is a PARP inhibitor that is not yet approved.
What are the biggest challenges in this setting?
One challenge lies in defining the patient population [that stands to benefit from these approaches]. The SOLO-1 trial only addressed maintenance therapy for patients with a BRCA mutation.
The second challenge is to understand the long-term benefit of maintenance therapy. The goal is to improve the cure rate. We don't have the answer [as to how to do that]. It may be difficult to find the answer regarding cure rate based on these clinical trials because the primary objectives of these studies are PFS. These are the important things we need to clarify.
What is your advice to clinicians treating a patient in need of frontline maintenance?
For now, it's to adhere to the SOLO-1 recommendation, meaning completing molecular testing in order to identify eligible patients. Additionally, we should give patients access to these studies, if available. For now, it's a bit too early to talk about the efficacy from any of the ongoing studies, so [we need to] make sure to follow the literature, publications, and the reports that come out at various medical meetings.