Shannon N. Westin, MD, MPH, on Ovarian Cancer: Results From the NOW Trial of Neoadjuvant Olaparib in BRCA-, PALB-, or RAD51C–Mutant Disease
SGO 2023 Annual Meeting on Women’s Cancer
Shannon N. Westin, MD, MPH, of The University of Texas MD Anderson Cancer Center, discusses results from the NOW study, which showed that neoadjuvant olaparib is feasible and has a good safety profile in patients with mutated, advanced-stage ovarian cancer. Even in patients with stage IV disease, surgical outcomes were favorable after two cycles of olaparib, justifying further study to determine whether PARP inhibitors can be given in lieu of chemotherapy in the neoadjuvant setting.
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
PARP inhibitors have completely revolutionized how we're treating ovarian cancer, first being explored in the treatment setting and now moving up into front-line maintenance. We were curious to see if utilizing PARP as a neoadjuvant treatment in lieu of chemotherapy might be reasonable in a population with germline-mutant ovarian cancer.
And so, we started a small feasibility study, because we really wanted to make sure the patients were safe, and the way we defined feasibility was either the lack of disease progression or lack of unacceptable toxicity, like a dose interruption in more than 2 weeks or requirement for two dose reductions. We allowed patients that had either a germline mutant BRCA, RAD51C, RAD51D, or PALB2 mutation, and were dispositioned to neoadjuvant chemotherapy. They could be dispositioned to the NOW trial, which was two cycles, so 2 months of olaparib as a single agent.
Importantly, we got tissue collection, both pre-treatment as well as after the two cycles of therapy. At that time, the patients were imaged and determined if they could move to surgery directly without any chemotherapy or if they needed further therapy. And our hope was that we would see the majority of patients being able to transition right to surgery.
The good news is, we were. Everybody was able to receive the two cycles. Only one patient required a dose reduction and a dose interruption. Of the patients that went right to surgery, there was 13 of them that were able to go right to surgery. So 86% didn't require any chemotherapy. And excitingly, amongst those patients that did have surgery, the optimal tumor reduction rate to no gross residual disease was 86%. So our ultimate goal was achieved. In addition, the remainder of the patients who had surgery all had optimal tumor reductions. And so we were very excited and intrigued by that. Now, we did even have one patient that had a pathologic complete response, so very exciting results there.
And when we looked at other markers of efficacy, we saw about 60% of patients had a response to therapy amongst those that had measurable disease, and importantly, 93% had a reduction in their CA125, including the best percent change of 81%. So we saw a huge drop in the tumor markers that indicate benefit from therapy.
So, small study, but very intriguing that we might be able to transition to a completely targeted therapy in the upfront setting for patients with germline mutations in the setting of advanced ovarian cancer. One of the other really exciting things we saw was patients were enthusiastic about it, and in fact, several of the patients declined to get any chemotherapy. They, instead, transitioned immediately to PARP inhibitor after their surgery. So, to be determined if this is truly a safe and effective option, but this will need to be explored in larger trials.
Ursula A. Matulonis, MD, of Dana-Farber Cancer Center discusses the ENGOT-OV16/NOVA study, which initially showed that niraparib maintenance therapy significantly prolonged progression-free survival in patients with platinum-sensitive recurrent ovarian cancer, regardless of germline BRCA mutation or homologous recombination deficiency biomarker status. Here, Dr. Matulonis details the final phase III findings on overall survival and the long-term safety of niraparib in this population.
Mansoor R. Mirza, MD, of Copenhagen’s Rigshospitalet, discusses phase III data from the ENGOT-EN6-NSGO/GOG-3031/RUBY study, which showed that, compared with carboplatin and paclitaxel alone, dostarlimab-gxly plus carboplatin and paclitaxel increased progression-free survival in patients with primary advanced or recurrent endometrial cancer that is mismatch repair–deficient/microsatellite instability–high. An early trend toward improved overall survival was observed in all populations. This regimen may represent a new standard of care for patients, says Dr. Mirza.
Shannon N. Westin, MD, MPH, of The University of Texas MD Anderson Cancer Center, discusses new findings on the combination of olaparib and selumetinib, which benefited patients with RAS-mutant ovarian and endometrial cancers. This combination will be explored further in these select cohorts in the upcoming ComboMATCH trial to clarify the relative contribution of each drug.