From new systemic therapy combinations in platinum-resistant ovarian cancer (PROC) to emerging targeted options for low-grade serous disease, a wave of clinical progress is expanding treatment possibilities, according to Brian Slomovitz, MD.
“This is a disease that didn’t have a lot of research going into it over the past couple years, but more recently, especially with the FDA approvals and other developments, the future is bright for better treatment options for patients with low-grade ovarian cancer,” Slomovitz said in an interview with OncLive®.
In the interview, Slomovitz emphasized surgical advances regarding minimally invasive procedures for patients with ovarian cancer, key trials that have read out recently in the platinum-resistant setting, and how the FDA approval of avutometinib plus defactinib (Avmapki Fakzynja Co-Pack) has redefined treatment for patients with previously treated, KRAS-mutated recurrent low-grade serous ovarian cancer.
He highlighted the clinical relevance of studies like the phase 3 ROSELLA trial (NCT05257408), data from which showed that the addition of relacorilant plus nab-paclitaxel (Abraxane; n = 188) improved progression-free survival (PFS) outcomes, generating a median PFS of 6.54 months (95% CI, 5.55-7.43) vs 5.52 (95% CI, 3.94-5.88) with nab-paclitaxel alone (n = 193) in patients with PROC (HR, 0.70; 95% CI, 0.54-0.91; P = .0076).1
He also noted findings from the phase 3 KEYNOTE-B96 trial (NCT05116189), which demonstrated that at the second interim analysis in the intention-to-treat population, the median PFS was 8.3 months with pembrolizumab plus paclitaxel (n = 322) vs 6.4 months with placebo plus paclitaxel (n = 321; HR, 0.73; 95% CI, 0.62-0.86).2
Slomovitz is the director of gynecologic oncology and cochair of the Cancer Research Committee at Mount Sinai Medical Center in Miami, Florida, as well as a professor of obstetrics and gynecology at Florida International University in Miami.
OncLive: What does the future look like for surgery developments in ovarian cancer?
Slomovitz: We’re learning more. [The MIRRORS-FROZEN trial (NCT06638593) is] ongoing to see if re-evaluated robotics can play a role vs open surgery. The ongoing phase 3 LANCE trial [NCT04575935] is investigating minimally invasive interval debulking surgery instead of an open procedure [in patients with stage IIIC to IV ovarian, primary peritoneal, or fallopian tube cancer]. We’ll learn a lot from that.
A lot of previous trials [investigated] neoadjuvant chemotherapy followed by interval debulking. We’re going to continue to learn more. We learned from the LION trial [NCT00712218] that you don’t need to do systemic lymphadenopathy for patients [with advanced ovarian cancer], but we’re going to continue to make progress, which we’re excited about.
What trials might signal future shifts in the PROC setting?
KEYNOTE-B96 Trial: Data Highlights From ESMO 2025
- The addition of pembrolizumab to weekly paclitaxel significantly improved PFS in the intention-to-treat population at the second interim analysis, reaching a median of 8.3 months compared with 6.4 months for the placebo group (HR, 0.73; 95% CI, 0.62-0.86; P < .0001).
- This trial represents the first phase 3 study in ovarian cancer to show a statistically significant overall survival (OS) benefit for an immune checkpoint inhibitor regimen, with the pembrolizumab arm achieving a median OS at the second interim analysis of 18.2 months (95% CI, 15.3-21.0) vs 14.0 months (95% CI, 12.5-16.1) in the population of patients with a PD-L1 combined positive score of at least 1 (HR, 0.76; 95% CI, 0.61-0.94; P = .0053).
- Although the incidence of grade 3 or higher treatment-related adverse effects was higher in the pembrolizumab group (67.5%) vs the placebo group (55.3%), the safety profile of the pembrolizumab combination remained consistent with those of the individual therapies.
The world of ovarian cancer continues to change. [One of] the most dramatic studies that we’ve seen of late is the [ROSELLA trial evaluating] relacorilant, a selective glucocorticoid receptor antagonist, [plus nab-paclitaxel in patients with advanced PROC]. Most recently, at the 2025 European Society for Medical Oncology (ESMO) Congress, we saw the KEYNOTE-B96 data with pembrolizumab [plus weekly paclitaxel in patients with PROC].
Both those studies used weekly taxanes. The ROSELLA trial used nab-paclitaxel, and KEYNOTE-B96 used weekly paclitaxel. They demonstrated overall survival advantages when adding agents—whether relacorilant or pembrolizumab—[to the taxanes]. That is exciting. Data with raludotatug deruxtecan [in PROC] were also presented [at ESMO 2025], and that’s exciting.
What long-term and ongoing research highlights advances in the platinum-sensitive ovarian cancer treatment paradigm?
In the platinum-sensitive setting, we’re going to be seeing maintenance trials, [such as] the rinatabart sesutecan [Rina-S; GEN1184] data from the phase 3 RAINFOL-04 study [NCT07225270] that’s open and ongoing. The Rina-S antibody-drug conjugate data in ovarian cancer are promising. There are so many good things going on.
The phase 3 PAOLA-1 trial [NCT02477644] data [showed] great first-line maintenance [results] in [patients who were] homologous recombination deficient or [with] BRCA [mutations] with olaparib [Lynparza] plus bevacizumab [Avastin]. The phase 3 SOLO-1 data [NCT01844986] withstood the test of time. The long-term follow-up data continue to show the advantage [of maintenance olaparib, which] is giving cures in some patients with [newly diagnosed, advanced] ovarian cancer, which is exciting.
What therapies are emerging for patients with low-grade serous ovarian cancer?
In low-grade serous ovarian cancer, the longer we investigate it, the more we realize it’s not at all like the typical high-grade serous ovarian cancers. If anything, it’s more like the hormone receptor–positive breast cancers. We need to come up with better treatment options. It’s not a very chemotherapy-sensitive disease. Hormonal therapy in the maintenance setting, as reported [in 2017] by David M. Gershenson, MD, [of The University of Texas MD Anderson Cancer Center in Houston], et al, probably has a benefit in preventing recurrences due to the disease.
But [2025] was an exciting year. We investigated the MEK/FAK inhibitor [combination avutometinib plus defactinib], and this received accelerated FDA approval [for the treatment of adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer who have previously been treated with systemic therapy. That was] encouraging. We’re still waiting for the phase 3 RAMP 301 trial [NCT06072781] data. This is a confirmatory trial to see whether [avutometinib plus defactinib] will be for all-comers or for the KRAS-mutated population. In addition, data [from the phase 2 GOG 3026 trial (NCT03673124), which] I’ve reported previously and which were accepted into the Journal of Clinical Oncology [in December 2025], evaluated the CDK4/6 inhibitor ribociclib [Kisqali] with letrozole in patients with recurrent disease. [This combination] generated an approximately 30% overall response rate.
References
- Lorusso D, Quesada S, Chan JK, et al. ROSELLA (GOG3073, ENGOTov72, APGOT-OV10): relacorilant + nab-paclitaxel in the subgroup of patients with platinum-resistant ovarian cancer (PROC) previously exposed to a PARP inhibitor. Ann Oncol. 2025;36(suppl 2):S1588-1589. doi:10.1016/j.annonc.2025.09.057
- Colombo N, Zsiros E, Sebastianelli A, et al. Pembrolizumab vs placebo plus weekly paclitaxel ± bevacizumab in platinum-resistant recurrent ovarian cancer: results from the randomized double-blind phase III ENGOT-ov65/KEYNOTE-B96 study. Ann Oncol. 2025;36(suppl 2):S1582. doi:10.1016/j.annonc.2025.09.049
