Trials of Interest in Ovarian Cancer

Chad Hamilton, MD: For the last part, we’re going to move quickly through a couple of trials of interest. Tom may have mentioned this trial a little bit earlier: The AVANOVA trial was an open-label, randomized phase 2 in recurrent platinum-sensitive, high-grade serous or endometrial cancer. It was designed to evaluate the combination of niraparib and bevacizumab versus niraparib alone, and this was as an alternative to cytotoxic chemotherapy.

The combination showed a significant improvement in progression-free survival [PFS], and this was both in the intent-to-treat population at 11.9 versus 5.5 months, and a number of prespecified exploratory analyses as well, including stratified by chemotherapy-free interval, be it 6 to 12 months and greater than 12 months. You can see the difference in PFS in those groups. We also saw a PFS difference in the exploratory analysis stratified by BRCA-mutated versus BRCA wild type as well as in the HRD [homologous recombination deficiency]-positive versus HRD-negative. We say HRP [homologous recombination proficient] versus HRD now. We’re all learning to change or unify our lingo when it comes to that. The overall response rate with the combination was 60% versus 27%, and the disease control rate was 79% versus 53%.

The last trial we’ll look at of our trials of interest is the randomized phase 2 BAROCCO trial. I give this one the nod for the best acronym. It’s the Best Approach in Recurrent Ovarian Cancer with Cediranib/Olaparib. BAROCCO. The trial evaluated a continuous versus intermittent dosing regimen of cediranib/olaparib in platinum-resistant ovarian cancer.

So, 89% of the patients in this trial were BRCA wild type or unknown. Over half of them had seen previous antiangiogenic treatment, and over half of them had 3 or more lines of chemotherapy. The primary end point was investigator-assessed PFS, and this was 3.1, 5.7, and 3.8 months, respectively, between the Taxol [paclitaxel], the continuous dosing of cediranib, and the intermittent dosing of cediranib. It’s interesting: the hazard ratios for PFS with continuous and intermittent therapy were 0.76 and 1.08, respectively. For the continuous regimen, the comparison was not proportional: the difference of the area under the curve [AUC] for the PFS actually came out to 1.25 months in favor of the continuous therapy with olaparib/cediranib combination. There is a lot to unbundle there on that slide and in this study as well, so we’ll wait to see more data coming from this.

This forest plot shows some of the subgroup analyses with a greater benefit with continuous combination therapy in BRCA wild type or unknown, and a similar trend was seen in patients who had received up to 2 prior lines of therapy and those with no previous antiangiogenic treatment. This KM [Kaplan-Meier] curve demonstrates the PFS in the BRCA wild type cohort, or BRCA wild type or unknown combination, with PFS of 2.1, 5.8, and 3.8 months in the paclitaxel continuous versus intermittent groups respectively, demonstrating that aforementioned trend favoring continuous and an AUC showing a difference of 1.82 months survival.

The hope was that, in this combination, the intermittent schedule, if equivalent, might improve the GI [gastrointestinal] tolerability as this treatment had been associated with a significant amount of GI toxicity and diarrhea in past trials. However, the toxicity profile of the study arms was pretty much as expected and similar between the experimental arms with 11%, 18%, and 7% discontinuing for adverse events.

There are certainly a lot more trials of interest out there, but for the sake of time, we’ll draw it to a close there and turn it back over to you, Shannon.

Shannon Westin, MD: Thank you so much, Chad. That was great. Thank you both for such a thoughtful discussion. These were great cases, and we got through many topics in a short period. I’m thankful to both of you for being here with me. To our viewing audience, I want to thank you for joining us for this Targeted Oncology Virtual Tumor Board® presentation. We hope today’s discussion was a valuable use of your time and that you acquired some practical knowledge that you can take back to your clinic. Thank you all for joining and please take care.

Transcript edited for clarity.