Impact of SOLO-1 on Advanced Ovarian Cancer Management

Transcript:

Michael Birrer, MD: SOLO-1 has had a significant impact on how we manage our ovarian cancer patients. First and foremost, the PFS [progression-free survival] data are remarkable. The experimental arm using olaparib has not reached median PFS yet, and we are out about 50 months. So for the first time in my career people are mumbling the “C” word, meaning cure. So I think that when I have a patient who has a BRCA1/BRCA2 mutation, whether somatic in the tumor or germline after their initial surgery and chemotherapy, I am offering them olaparib.

Ursula A. Matulonis, MD: For patients who are newly diagnosed, they are eligible for olaparib maintenance if they have advanced disease, so stage III or stage IV cancer; if they have a deleterious BRCA mutation, and that can either be germline or somatic; if they have a response to upfront chemotherapy; if they have adequate blood counts; and if they don’t have any evidence of AML [acute myeloid leukemia] or MDS [myelodysplastic syndrome]. Those patients are eligible to receive olaparib.

Michael Birrer, MD: SOLO-1 results have also changed the way we’ve managed genetic testing of our patients. As I said previously, we believe all ovarian cancer patients should be sequenced, tumor and germline. Despite that, and despite the fact that SGO [the Society of Gynecological Oncology] and ASCO [the American Society of Clinical Oncology] and IGCS [the International Gynecologic Cancer Society] all recommend this, we are only sequencing 30% to 40% of our patients. SOLO-1 has actually changed that because SOLO-1 has provided evidence that for those patients who have abnormalities in BRCA1 and BRCA2, you can now offer an effective additional therapy. We have noted that investigators are more inclined to do the right thing, which is sequence both the germline and somatic mutations.

I think that for 2 reasons, both in terms of therapeutic efficacy and because it’s necessitating genetic testing, SOLO-1 has had a large impact on the way we manage patients. Ultimately, this may have consequences down the line because patients getting into their second remission may have already had olaparib and PARP [poly ADP ribose polymerase] inhibitors, and so we probably will begin to see a larger proportion of our patients who have PARP resistance.

Ursula A. Matulonis, MD: The role of PARP inhibitors is expanding. Initially, the first PARP inhibitor approval in the United States was using these drugs as single agents in patients with relapsed, more heavily pretreated BRCA-mutated ovarian cancer. The first approval was olaparib in December of 2014, and those are patients who have a germline BRCA mutation and who had received at least 3 prior lines of chemotherapy. Rucaparib was second for patients who either had a germline or somatic BRCA mutation and have received 2 lines of more of prior chemotherapy. The second approval came with maintenance therapy, and now we’ve got 3 maintenance drugs: olaparib, niraparib, and rucaparib. And then thirdly with the publication and presentation of the SOLO-1 results, women with newly diagnosed advanced stage BRCA-mutated ovarian cancer who are in response to chemotherapy can receive olaparib as maintenance.

Now, I think with the use of PARP inhibitors really infiltrating how we manage upfront ovarian cancer—at least right now for those who have patients who have BRCA-mutated cancer—how we use PARP inhibitors in recurrence, if those patients do recur, is an evolving field. So, if patients have a certain duration of time off the PARP inhibitor and we reuse it, we’ll have to see the efficacy through clinical trials. Should we be using PARP inhibitor combinations, PARP inhibitors combined with anti-angiogenic medications, PI3-kinase medications, or immunotherapy drugs? Clinical trials will tell us.

Transcript Edited for Clarity.