Introduction

Platinum-resistant ovarian cancer remains one of the more difficult clinical scenarios in gynecologic oncology, with a historical overall survival of roughly one year and limited options beyond weekly paclitaxel with or without bevacizumab. Three studies presented this year, ROSELLA, CHIPRO, and ENGOT-ov65/KEYNOTE-B96, each add a new combination option to that landscape, and together they raise a practical question clinicians will increasingly face: with several new choices now available, how should treatment be sequenced for an individual patient?

ROSELLA: Relacorilant Adds Benefit Regardless of Prior Taxane Exposure

Relacorilant is a selective glucocorticoid receptor antagonist. The biological rationale is that cortisol-mediated survival signaling through the glucocorticoid receptor contributes to chemotherapy resistance in ovarian cancer, and blocking that receptor may restore taxane sensitivity, including in patients previously treated with a taxane.

ROSELLA, a phase 3 trial, randomized patients with platinum-resistant ovarian cancer (who had received prior bevacizumab) to relacorilant plus nab-paclitaxel or nab-paclitaxel alone. Nab-paclitaxel was chosen deliberately as the backbone because, unlike other taxanes, it does not require steroid premedication, which would otherwise work against a glucocorticoid receptor antagonist. The trial had previously reported a positive primary analysis, with median progression-free survival of 6 months versus 5.5 months. At the final analysis, presented this year, overall survival was extended by 4.1 months (HR, 0.65), a 35% reduction in the risk of death from any cause. Critically, this analysis focused on whether prior taxane exposure blunted the benefit, and it did not: overall survival favored relacorilant plus nab-paclitaxel regardless of whether the taxane-free interval was less than or more than six months. Hematologic toxicity and peripheral neuropathy were similar between arms, with somewhat more neutropenia in the relacorilant arm, attributed to longer treatment duration rather than a true safety signal.

ROSELLA met both of its dual primary endpoints (PFS and OS) and requires no biomarker for patient selection, which makes it broadly applicable. It was approved in March 2026 for platinum-resistant ovarian cancer and represents a new standard option, particularly relevant given how many patients in this setting have already been through a taxane.

CHIPRO: Chiauranib Plus Weekly Paclitaxel

CHIPRO, a phase 3 study conducted in China, tested chiauranib, an oral multi-target tyrosine kinase inhibitor with activity against Aurora B, CSF1R, PDGFR, DDR1, and VEGFR, in combination with weekly paclitaxel against placebo plus weekly paclitaxel in platinum-resistant or refractory ovarian cancer. The mechanistic rationale is broader than most single-target agents: Aurora B inhibition drives G2/M arrest and apoptosis, while the additional kinase targets work to reprogram the tumor microenvironment and block angiogenesis.

Progression-free survival, the primary endpoint by independent central review, was significantly improved with chiauranib plus paclitaxel, at a median of 4.57 months versus 2.69 months (hazard ratio favoring the combination, P<.001). The PFS benefit held consistently across subgroups, including regardless of prior anti-angiogenic therapy or prior PARP inhibitor use. Overall survival, a secondary end point, showed no statistically significant difference between two groups. However, we did observe some interesting trends in specific subgroups. For example, among patients who did not receive subsequent anticancer therapy, an overall survival benefit was seen, with survival being nearly three months longer than in the placebo group.

Secondly, in patients with prior PARP inhibitor exposure, there was a favorable trend toward improved overall survival.

Third, among patients who subsequently received platinum therapy, the CP subgroup had a prolonged median platinum-free interval compared with the placebo group, along with a trend toward improved overall survival.

Additionally, the objective response rate in the CP group was higher, and the duration of response was also significantly longer compared with the placebo group.

As expected, grade 3 or higher treatment-related adverse events were more frequently observed in the CP group, leading to more dose interruptions and dose reductions. However, there was no significant increase in treatment discontinuation in the CP group.

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ENGOT-ov65/KEYNOTE-B96: Pembrolizumab Plus Weekly Paclitaxel

Building on the AURELIA trial, which established bevacizumab plus weekly paclitaxel as the most effective backbone chemotherapy regimen in platinum-resistant ovarian cancer, ENGOT-ov65/KEYNOTE-B96 tested the addition of pembrolizumab to weekly paclitaxel, with or without bevacizumab, against placebo, in patients who had received one to two prior lines of therapy including a platinum agent.

At the final analysis, pembrolizumab plus weekly paclitaxel (with or without bevacizumab) showed a statistically significant and clinically meaningful improvement in progression-free survival in both the PD-L1 CPS ≥1 population and the intention-to-treat population, with roughly a 13% absolute PFS benefit in each. Overall survival was also significantly improved, both in the CPS ≥1 population and in the intention-to-treat population, one of the longest overall survival results reported in any trial for this disease setting. Grade 3 or higher adverse events were more frequent with pembrolizumab, primarily hypothyroidism and infusion reactions, and there were a small number of deaths attributed to treatment-related pneumonitis and colitis; chemotherapy-related toxicities (anemia, peripheral neuropathy, alopecia) were consistent with expectations, and no dose discontinuations were attributed to these events.

This is the first phase 3 trial to show a statistically significant overall survival improvement in both the CPS ≥1 and intention-to-treat populations for platinum-resistant, recurrent ovarian cancer, supporting pembrolizumab plus weekly paclitaxel, with or without bevacizumab, as a new standard-of-care option.

Choosing Among Three New Options

With ROSELLA, CHIPRO, and now ENGOT-ov65/KEYNOTE-B96 all showing benefit in overlapping patient populations, alongside the previously established mirvetuximab soravtansine option in FRα-high disease (MIRASOL), sequencing decisions increasingly depend on biomarker testing. A reasonable framework: check FRα expression and consider mirvetuximab first if expression is high (≥75%), particularly to spare additional taxane exposure and its cumulative neuropathy risk; below that threshold, relacorilant plus nab-paclitaxel is a strong option regardless of prior taxane exposure. Where PD-L1 CPS status and disease biology support it, pembrolizumab plus weekly paclitaxel, with its now-demonstrated overall survival benefit, is an increasingly compelling choice. As these trials mature and more real-world data emerges, comparative and biomarker-driven sequencing strategies will likely become clearer.

For Patients

For people with platinum-resistant ovarian cancer, three new drug combinations, relacorilant plus nab-paclitaxel, chiauranib plus paclitaxel, and pembrolizumab plus paclitaxel, have each shown meaningful benefit in recent clinical trials, adding real options to what has historically been a difficult-to-treat stage of disease. Relacorilant's benefit does not depend on whether a patient has previously received a taxane chemotherapy drug. Pembrolizumab's combination showed one of the longest survival improvements reported in this setting to date.

With several new options now available, choosing the right one increasingly depends on specific tumor testing, including a marker called folate receptor alpha and PD-L1 status, so a detailed conversation with a gynecologic oncology team about individual test results is worthwhile before deciding on a treatment path.

Key Takeaways

  • ROSELLA's final analysis showed a 4.1-month overall survival benefit (35% reduction in risk of death) with relacorilant plus nab-paclitaxel, consistent regardless of prior taxane exposure; it requires no biomarker for selection and was approved in March 2026.

  • CHIPRO showed a significant PFS benefit (4.57 vs 2.69 months) with chiauranib plus weekly paclitaxel in a primarily platinum-refractory population, though overall survival was not significantly different between arms.

  • ENGOT-ov65/KEYNOTE-B96 showed significant PFS and OS benefit with pembrolizumab plus weekly paclitaxel (± bevacizumab), the first phase 3 trial to show a significant OS improvement in both CPS ≥1 and intention-to-treat populations in this setting.

  • With three new regimens now available alongside mirvetuximab soravtansine, biomarker testing (FRα, PD-L1 CPS) is increasingly central to sequencing decisions in platinum-resistant ovarian cancer.

References

  1. Gilbert L, You B, Olawaiye AB, et al. Overall survival subgroup analyses for prior taxane use in the phase 3 ROSELLA trial of relacorilant plus nab-paclitaxel vs nab-paclitaxel monotherapy in patients with platinum-resistant ovarian cancer. Presented at: 2026 ASCO Annual Meeting.

  2. Wu X, Li J, Wang D, et al. A phase III CHIPRO study of chiauranib plus weekly paclitaxel for platinum-resistant or refractory ovarian cancer. Presented at: 2026 ASCO Annual Meeting.

  3. Colombo N, Zsiros E, Sebastianelli A, et al. Pembrolizumab vs placebo plus weekly paclitaxel ± bevacizumab in platinum-resistant recurrent ovarian cancer: final analysis results from the randomized double-blind phase 3 ENGOT-ov65/KEYNOTE-B96 study. Presented at: 2026 ASCO Annual Meeting.