Bradley J. Monk, MD: The next discovery, published in the New England Journal of Medicine, led to olaparib use in patients with BRCA-associated disease. We have Katie Moore here, who was the first author published in the New England Journal of Medicine related to the approval in December 2018. Tell us about that study and what that has meant to our practice in the frontline setting.
Kathleen N. Moore, MD: As you know, I love to talk about SOLO-1. SOLO-1 was a randomized phase 3 study that enrolled only women with BRCA-associated cancers, predominantly germline mutations in BRCA. They had to have advanced cancer, an attempted cytoreductive surgery, and at the end of platinum-based chemotherapy, complete or partial response to chemotherapy. At this point they were randomized 2 to 1 to receive olaparib tablets versus placebo until progression or toxicity or the 2-year mark. The primary end point was investigator-assessed progression-free survival [PFS].
That took a long time to reach, but it finally resulted and demonstrated a ratio of 0.3, which translated to a difference in the median progression-free survival—counted from the end of chemotherapy, importantly—of 13.8 months in the control arm and not yet reached in the arm that was treated with olaparib, but it is somewhere around 47 to 49 months. The PFS2 [PFS after 2 lines of therapy] was positive as well. There have been several subsequent exploratory analyses in all the different surgical and residual disease subgroups, demonstrating equal magnitude of benefit regardless of how you analyze it. That appropriately led to a change in the standard of care for these women.
Bradley J. Monk, MD: When you say standard of care, I define that as what reasonable physicians would do in a similar setting. It doesn’t mean it’s the only standard of care. Tom Krivak, is this the only standard of care if you have a BRCA mutation to get a PARP inhibitor?
Thomas C. Krivak, MD: I hate using the term standard of care, but I know we use it a lot. Given how the question is phrased, I would say that you must have a reason not to give it. To me, when you look at those data, they’re just so impressive that I completely agree. Sometimes there’s a slow adoption, but to not be on this therapy with the germline mutation as well as somatic mutation, I get nervous. I think if you would show patients some of these Kaplan-Meier curves when they say, “I don’t think I really need it,” and you ask if they want to be on the top line or bottom line, there is such separation that most patients would say, “I don’t understand why you aren’t making me take this.”
Bradley J. Monk, MD: Right.
Thomas C. Krivak, MD: I would say that you really have to have a strong reason not to be using a PARP inhibitor in a patient who has a BRCA mutation at this time.
Bradley J. Monk, MD: Katie, I know you like to talk about this, and we like to listen to you. That’s a great opportunity. You presented this all around the world, and we love it. Do you ever present it and people say, “Well, I’m not sure”? Never, right?
Kathleen N. Moore, MD: Oh, no, I do hear that.
Bradley J. Monk, MD: Why do people say that? Tell us. That’s what I’m trying to discuss here.
Thomas J. Herzog, MD: The save-it-for-later crowd.
Kathleen N. Moore, MD: The save-it-for-later crowd. I had the opportunity to debate someone who is really a believer in that at the NRG Oncology Semiannual Meeting this year. I’ve been convinced there’s just no rationale for that. I’ve stopped being nice about it because I don’t want it to even be considered an equivalent option. We should have learned that message from the bevacizumab story, which you just demonstrated. The argument is you look at SOLO-1 and SOLO2 and the hazard ratios are both 0.3, so someone says, “Well, I can use it here and now or later, and I get the same benefit,” which assumes you’re going to let your patient recur. I don’t know why you would let your patient recur, No. 1; and No. 2, those are 2 completely different lines of therapy. If you look at the same thing with bevacizumab but lined up frontline and second line—such as OCEANS or GOG-0213 and then AURELIA—and use that rationale, you would say, “Well, I would use only it in the AURELIA setting,” which is asinine. Why would you wait in your highest-risk population? It is a good drug there, but your frontline is where you have the opportunity to cure somebody. It makes no sense, and the argument makes no sense. It makes my head explode.
Bradley J. Monk, MD: Before we offend too many people, I’m going to stop you there. But that’s great. Thank you for your hard work on that. I look at it as an unprecedented result. Whatever the definition of standard of care is, we have an obligation to discuss that with our patients. The obligation begins with germline and somatic testing, because if you don’t test, you won’t have the opportunity.
Transcript Edited for Clarity