Michael J. Birrer, MD, PhD
The PARP inhibitor olaparib (Lynparza) continued to show significant promise as an agent for patients with platinum-sensitive ovarian cancer and germline BRCA
mutations, according to secondary analyses of the SOLO2 study presented at the 2017 ASCO Annual Meeting.
Patient-reported outcomes demonstrated an improvement in progression-free survival (PFS) with no decrement in health-related quality of life (QOL) during maintenance therapy with olaparib.1
During a mean follow-up of 12 months, the average score on the Functional Assessment of Cancer Therapy-Ovarian Trial Outcome Index did not change significantly from baseline among patients treated with olaparib and did not differ from the control group. However, the duration of time with disease-related symptoms or toxicity was found to be significantly longer in olaparib-treated patients.
Moreover, a second abstract focused on an expanded analysis of adverse events (AEs), which was the first clinical evaluation of a tablet formulation of olaparib.2
Prior studies used a capsule formulation. The analysis focused on greater detail of the initial SOLO2 AEs with the new olaparib formulation— nausea, vomiting, fatigue/asthenia, and anemia—all of which were consistent with prior studies of olaparib.
In an interview with OncLive
during the 2017 ASCO Annual Meeting, Michael J. Birrer, MD, PhD, who is now medical director at the University of Alabama at Birmingham Comprehensive Cancer Center, discussed some of the exciting data presented at the meeting—especially with olaparib in SOLO2—and what other emerging advancements are poised to transform the landscape.
OncLive: SOLO2 was a pivotal trial of olaparib in ovarian cancer. Can you give some background on this study?
: SOLO2 is an exciting time. The efficacy data was presented at the 2017 Society of Gynecologic Oncology meeting a couple of months ago. The SOLO2 data follows and looks a lot like Study 19 but, in fact, the data are even better. Therefore, the placebo arm had a median PFS of about 5 months. This is consistent with all of the placebo-controlled maintenance trials, which are between 4 and 5 months. However, the olaparib-treated arm was about 19 months. That is a whopping prolongation of PFS, and that was the investigator analysis. If you look at the independent radiologic review, it actually goes out until about 30 months. It is a very positive trial. It is going to the FDA, and I have no doubt that this drug will be approved [in the maintenance setting].
What QOL data were presented at the 2017 ASCO Annual Meeting?
The QOL data basically follows with what you would expect. Patients who are on olaparib maintenance do well. There was a concern about the formulation because the old capsule requires the patients to take 16 pills a day. That is a lot of pills; the tablet form is a much lower [amount]. Thus far, it looks like the tablets are going to be a home run.
AE data were also presented. Can you comment?
The AE data are what you would expect from a PARP inhibitor. There is some fatigue and nausea [reported]. The nausea disappears after a while, and there is some mild myelosuppression. That is about it.
This fits Dr Birrer’s definition of a good maintenance drug. It is easy to take, it’s convenient, it has minimal side effects, and it is efficacious.
There have been recent developments with mirvetuximab soravtansine. What is the promise with this drug?
One of the hot new drugs for the treatment of ovarian cancer is mirvetuximab soravtansine, which is an antibody-drug conjugate targeting the folate receptor alpha. This drug has gone through phase I testing and into an expansion cohort—with what I would say are very impressive data. Response rates in platinum-resistant ovarian cancer are in the range between 40% and 50%. The toxicity profile is outstanding. There is, essentially, no bone marrow suppression and no neuropathy. There is an interesting toxicity involving blurred vision, but it is completely manageable and completely reversible.
A lot of us have worked on this project, in this program, and are very excited about it. Based on that data, it is now being investigated in an FDA registration trial called FORWARD I, which is a randomized trial between standard of care, which would be single-agent chemotherapy, doxorubicin, topotecan, or weekly paclitaxel, versus single-agent mirvetuximab soravtansine.