A Glimpse at Practice-Shifting Presentations at The 2025 SGO Annual Meeting

Tomorrow, experts in gynecologic oncology will convene in Seattle, Washington to present key developments and research efforts in the field as part of the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO). The meeting will feature a variety of multidisciplinary oncology professionals who are geared to detail findings that may impact the management of ovarian cancer, cervical cancer, endometrial cancer, and other gynecologic malignancies.

Here are some of the topics and sessions that may inform treatment planning for patients with different gynecologic cancers:

(ENCORE) Avutometinib + defactinib in recurrent low grade serous ovarian cancer (ENGOT-OV60/GOG-3052/RAMP 201): dose-intensity and subgroup analysis

This year’s SGO meeting will feature an encore of subgroup analysis data from the phase 2 RAMP 201 trial (NCT04625270) evaluating the RAF/MEK inhibitor avutometinib in combination with the FAK inhibitor defactinib for adults with recurrent low-grade serous ovarian cancer. These findings related to dose intensities and patient subgroups may build upon prior outcomes achieved with the avutometinib regimen and have regulatory implications.

The FDA previously accepted a new drug application for avutometinib/defactinib as a treatment for this patient population, specifically those with KRAS-mutated disease and who received at least 1 prior line of treatment, in December 2024 based on findings from the RAMP 201 trial.¹ If approved, the avutometinib combination would become the first commercially available treatment for patients with recurrent KRAS-mutated low-grade serous ovarian cancer.

Investigators previously presented primary analysis data from the trial at the International Gynecologic Cancer Society (IGCS) 2024 Annual Meeting.² Data from the primary analysis showed a confirmed overall response rate (ORR) of 31% (n = 34/109; 95% CI, 23%-41%) after a follow-up of approximately 12 months and a data cutoff date of June 30, 2024. Additionally, the ORR was 44% (n = 25/57; 95% CI, 31%-58%) in patients with KRAS-mutant disease and 17% (n = 9/52; 95% CI, 8%-30%) in those with KRAS wild-type disease.

Final overall survival analysis among patients with folate receptor alpha-positive, platinum-resistant ovarian cancer treated with mirvetuximab soravtansine versus investigator's choice chemotherapy in phase II MIRASOL (GOG-3045/ENGOT-ov55) study

One presentation will highlight updated overall survival (OS) findings from the phase 3 MIRASOL trial (NCT04209855) assessing mirvetuximab soravtansine-gynx (Elahere) vs chemotherapy for patients with folate receptor alpha (FRα)–positive platinum-resistant epithelial ovarian cancer. Data from this final analysis may affirm the benefits observed with earlier reports of mirvetuximab soravtansine that led to the agent’s FDA approval for previously treated FRα–positive platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer in March 2024.³

Additionally, in a poster presentation at the 2024 European Society for Medical Oncology (ESMO) Congress, investigators highlighted OS findings after a median follow-up of 20.3 months (range, 19.3-21.4).⁴ At the time of this analysis, the median OS was 16.46 months (95% CI, 14.36-19.88) with mirvetuximab vs 13.34 months (95% CI, 11.37-15.44) with chemotherapy (HR, 0.67; 95% CI, 0.53-0.86; P = .0011).

Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: overall survival and progression-free survival 2 results from the randomized, double-blind, phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 study

In another plenary session, additional OS and progression-free survival (PFS)-2 data from the phase 3 KEYNOTE-A18 trial (NCT04221945) trial will be detailed. As part of this randomized, placebo-controlled trial, investigators assessed pembrolizumab (Keytruda) in combination with chemoradiotherapy (CRT) vs placebo/CRT among patients with newly diagnosed, previously untreated, high-risk, locally advanced cervical cancer.

Prior findings presented at the 2024 ESMO Congress showed that the OS rate at 36 months was 82.6% (95% CI, 78.4%-86.1%) in the pembrolizumab arm vs 74.8% (95% CI, 70.1%-78.8%) in the placebo arm.⁵ The median OS was not reached (NR) in both arms at the time of analysis (HR, 0.67; 95% CI, 0.50-0.90; P = .0040).

Previously, the FDA approved pembrolizumab plus external beam radiotherapy, concurrent chemotherapy, and brachytherapy for patients with FIGO stage III to IVA cervical cancer based on findings from the KEYNOTE-A18 trial.⁶

Durvalumab plus carboplatin/paclitaxel followed by durvalumab with/without olaparib in endometrial cancer: Biomarkers, histological heterogeneity, baseline circulating tumor DNA and efficacy in the DUO-E mismatch repair proficient subpopulation

Another late-breaking abstract presentation will offer a closer look at outcomes achieved with a durvalumab (Imfinzi)-based regimen in a subgroup of patients with mismatch repair proficient (pMMR) advanced or recurrent endometrial cancer enrolled in the phase 3 DUO-E trial (NCT04269200).

These findings may build upon data presented at the 2024 SGO Annual Meeting, in which durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab with or without olaparib (Lynparza) improved PFS vs chemotherapy alone regardless of mismatch repair status.⁷

Across the intent-to-treat population, the median PFS was 9.6 months (95% CI, 9.0-9.9) with chemotherapy alone vs 10.2 months (95% CI, 9.7-14.7) with chemotherapy/durvalumab (HR, 0.71; 95% CI, 0.57-0.89; P = .003). With the addition of maintenance olaparib to durvalumab/chemotherapy, the median PFS was 15.1 months (95% CI, 12.6-20.7), reducing the risk of progression or death vs chemotherapy alone (HR, 0.55; 95% CI, 0.43-0.69; P <.0001) and chemotherapy/durvalumab (HR, 0.71; 95% CI, 0.57-0.89; P = .003).

Of note, the FDA approved durvalumab plus chemotherapy followed by durvalumab maintenance for adults with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) in June 2024 based on prior findings from the DUO-E trial.⁸

According to a press release issued by SGO, this study “underscores the importance of biomarker-driven treatment” and shows that “by identifying which patients are most likely to benefit from combination therapy, providers can better tailor treatments and improve outcomes.”⁹

Chemotherapy with or without pembrolizumab followed by maintenance with olaparib or placebo for first-line treatment of advanced BRCA non-mutated epithelial ovarian cancer: results from the randomized phase 3 ENGOT-OV43/GOG-3036/KEYLYNK-001 study

Another plenary session will reveal detailed outcomes from the double-blind phase 3 KEYLYNK-001 study (NCT03740165) investigating pembrolizumab plus chemotherapy followed by pembrolizumab and maintenance olaparib with or without bevacizumab (Avastin) as frontline therapy for BRCA non-mutated advanced epithelial ovarian cancer.

According to a press release in December 2024, a prior analysis conducted by an independent data monitoring committee showed that pembrolizumab-based treatment elicited a statistically significant and clinically meaningful improvement in the primary end point of PFS.¹⁰ The secondary end point of OS was not reached at the time of this analysis.

The press release stated that investigators intend to discuss findings from the KEYLYNK-001 study with regulatory authorities. Specific data highlighted at the 2025 SGO Meeting may support a regulatory pathway for the pembrolizumab-based regimen in this epithelial ovarian cancer population.

References

1. Verastem Oncology announces FDA acceptance and priority review of new drug application for avutometinib in combination with defactinib for the treatment of recurrent KRAS mutant low-grade serous ovarian cancer. News release. Verastem Oncology. December 30, 2024. Accessed March 11, 2025. https://tinyurl.com/57brbv3n
2. Verastem Oncology presents positive updated RAMP 201 data for avutometinib and defactinib combination in recurrent low-grade serous ovarian cancer at the International Gynecologic Cancer Society (IGCS) 2024 Annual Meeting. News release. Verastem Oncology. October 17, 2024. Accessed March 11, 2025. https://tinyurl.com/zuxdeuwh
3. FDA approves mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. News release. FDA. March 22, 2024. Accessed March 11, 2025. https://tinyurl.com/2apx6e5s
4. Coffman LG, You B, Hamilton EP, et al. 746P Phase III MIRASOL trial: updated overall survival results of mirvetuximab soravtansine (MIRV) vs. investigator’s choice chemotherapy (ICC) in patients (pts) with platinum-resistant ovarian cancer (PROC) and high folate receptor-alpha (FRα) expression. Ann Oncol. 2024;35(suppl 2):S566. doi:10.1016/j.annonc.2024.08.807
5. Lorusso D, Xiang Y, Hasegawa K, et al. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. Published online September 14, 2024. doi:10.1016/S0140-6736(24)01808-7
6. FDA approves pembrolizumab with chemoradiotherapy for FIGO 2014 stage III-IVA cervical cancer. News release. FDA. January 12, 2024. Accessed March 11, 2025. https://shorturl.at/pswHW
7. Chon HS, Thomas-Pepin J, Sundborg MJ, et al. Durvalumab plus carboplatin/paclitaxel followed by durvalumab with or without olaparib as first-line treatment for endometrial cancer (DUO-E/GOG-3041/ENGOT-EN10): objective response rate and duration of response by mismatch repair status. Presented at: SGO 2024 Annual Meeting on Women’s Cancer; March 16-18, 2024; San Diego, CA.
8. FDA approves durvalumab with chemotherapy for mismatch repair deficient primary advanced or recurrent endometrial cancer. News release. FDA. June 14, 2024. Accessed March 11, 2025. https://tinyurl.com/mvhx997f
9. Press release 6: personalized approaches to endometrial cancer detection and treatment. News release. SGO. Accessed March 12, 2025. https://tinyurl.com/mrypjtjn
10. Merck announces phase 3 KEYLYNK-001 trial met primary endpoint of progression-free survival (PFS) in patients with advanced epithelial ovarian cancer. News release. Merck. December 9, 2024. Accessed March 11, 2025. https://tinyurl.com/yty2r89a