📬 GYN Oncology Intelligence Digest — Week 2026-W37

XPORT-EC-042 selinexor maintenance reads out negative in p53 wild-type endometrial cancer (12.75 vs 7.43 mo, HR 0.76), KEYNOTE-C93 shows single-agent PD-1 blockade beating chemotherapy front-line in dMMR endometrial cancer, rezatapopt hits a 46% ORR in TP53 Y220C platinum-resistant ovarian cancer with a filing planned for Q1 2027, and FDA fast track goes to sapanisertib/serabelisib plus paclitaxel in PI3K/AKT/mTOR-altered endometrial cancer.

⚡ TL;DR

🐦 Twitter / 🦋 Bluesky

XPORT-EC-042 selinexor maintenance is negative in p53 wild-type endometrial cancer despite the SIENDO signal — The topline XPORT-EC-042 result in p53 wild-type endometrial cancer was 12.75 vs 7.43 months, HR 0.76, 95% CI 0.51-1.12, while the earlier SIENDO p53 wild-type subgroup had shown HR 0.41
B7-H4 and B7-H3 ADCs and immune-priming ADC combinations move into endometrial and ovarian cancer — B7-H4 and B7-H3 are described as overexpressed in both ovarian and endometrial cancers, making them ideal ADC targets
RSF1 identified as an H2Aub reader sustaining ovarian cancer stemness and relapse — The study identifies RSF1 as an H2Aub reader that sustains cancer stemness, revealing the RSF1-H2Aub interaction as a therapeutic vulnerability in ovarian cancer relapse
FDA fast track for sapanisertib plus serabelisib and paclitaxel in PI3K/AKT/mTOR-altered endometrial cancer — Sapanisertib and serabelisib plus paclitaxel received FDA fast track designation for pretreated advanced PI3K/AKT/mTOR pathway-altered endometrial cancer
Racial survival disparities in endometrial cancer: a 159% higher death risk under 65, and unexplained residual disparity in insured patients over 65 — Black women less than 65 years old with endometrial cancer have 159% greater risk for death than white women

Full details below ↓

📄 What's Being Published

Manuscripts:

Secondary cytoreduction for ovarian cancer relapse: results from the high surgical quality, multi-center "Surgery in Recurrent Ovarian Cancer Research Consortium (SURROC-CON)". — du Bois Andreas et al., Int J Gynecol Cancer

In this multi-center analysis of 3109 patients with recurrent ovarian cancer, 38.7% underwent secondary cytoreduction and 83.6% achieved complete clearance. Median overall survival was 81 months (95% CI 73 to 88) after complete clearance versus 39 months (95% CI 33 to 44) with residual disease (p <.001), compared with 34 months (95% CI 33 to 36) with chemotherapy alone. Prior maintenance therapy was prognostic: median overall survival without previous maintenance was 73 months versus 55 months after previous bevacizumab versus 44 months after previous PARP inhibitors (p =.0056), while BRCA1/2 mutations were associated with improved progression-free survival after secondary cytoreduction (27.4 vs. 21.3 months, p <.0021) but not overall survival.

Clinical bottom line: Prior maintenance therapy matters — patients who had received PARP inhibitors or bevacizumab had shorter post-surgical overall survival — while BRCA status and timing of initial cytoreduction did not change the benefit, so complete gross resection at a high-volume center remains the only thing worth operating for.

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Clinical outcomes and prognostic factors in advanced high-grade platinum-resistant ovarian carcinoma: evidence from the ESME real-world cancer database. — Heurtier Victor et al., Int J Gynecol Cancer

Among 688 patients with platinum-resistant high-grade ovarian carcinoma, 580 (84.3%) received chemotherapy alone and 108 (15.7%) received chemotherapy plus bevacizumab; median progression-free survival and overall survival were 3.2 and 8.8 months across the cohort. In the chemotherapy-alone group, gemcitabine was associated with inferior progression-free survival compared with paclitaxel (2.5 vs 3.4 months; HR 1.31; 95% CI 1.03 to 1.67), and in the bevacizumab group, median progression-free survival was 6.5 months with paclitaxel plus bevacizumab compared with 4.1 months with pegylated liposomal doxorubicin plus bevacizumab (HR 3.50, 95% CI 1.93 to 6.34) and 3.6 months with gemcitabine plus bevacizumab (HR 2.54, 95% CI 1.10 to 5.88). In the multivariable model, bevacizumab was independently associated with improved overall survival (HR 0.73, 95% CI 0.56 to 0.94).

Clinical bottom line: In this 688-patient real-world cohort, paclitaxel is the backbone to pair with bevacizumab in platinum-resistant disease, while the apparent independent bevacizumab survival benefit (HR 0.73) should be read as likely confounding by indication rather than proof of effect.

Read full article →

🗂 Every paper considered this week, including the ones that didn’t make it →

🗣️ What People Were Discussing This Week

How these are chosen: filtered for clinical relevance, grouped by the new development discussed, then ordered by engagement (bookmarks and reposts).

XPORT-EC-042 selinexor maintenance is negative in p53 wild-type endometrial cancer despite the SIENDO signal

The topline XPORT-EC-042 result in p53 wild-type endometrial cancer showed 12.75 vs 7.43 months, HR 0.76, 95% CI 0.51–1.12 — a negative trial, despite the earlier SIENDO p53 wild-type subgroup having shown HR 0.41. Mechanistically, selinexor blocks XPO1 and keeps wild-type p53 in the nucleus, so mutated tumors give the drug nothing to hit, and the biology of the enriched population was sound. An accompanying editorial frames the next challenge in advanced or recurrent endometrial cancer as moving from intensification to selection — and the debate is whether the failure here belongs to the biomarker or to a maintenance setting where quiescent disease may simply not provide enough target for the drug to engage.

Discussed by: @DrBarbiOnc, @IJGConline

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B7-H4 and B7-H3 ADCs and immune-priming ADC combinations move into endometrial and ovarian cancer

B7-H4 and B7-H3 are overexpressed in both ovarian and endometrial cancers, making them candidates for antibody-drug conjugate targeting, as noted by Dr. Dana Chase of UCLA Health Jonsson Comprehensive Cancer Center. In the phase 1/2 BEHOLD-2 trial, mocertatug rezetecan's immune-activating mechanism is paired with dostarlimab in an attempt to make cold endometrial tumors respond to immunotherapy, with Angeles Alvarez Secord detailing the rationale. The active question is which ADC target — folate receptor alpha, B7-H4/B7-H3, or CDH6 — earns the second-line slot, and whether immune priming justifies combining an ADC with a checkpoint inhibitor.

Discussed by: @OncLive, @OncLive

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RSF1 identified as an H2Aub reader sustaining ovarian cancer stemness and relapse

A new study identifies RSF1 as an H2Aub reader that sustains cancer stemness, with the RSF1–H2Aub interaction described as a therapeutic vulnerability in ovarian cancer. The work links cancer stemness directly to ovarian cancer relapse and tumor plasticity. Whether an epigenetic reader like RSF1 can be drugged in time to matter for a relapse-prone population is the central unresolved question.

Discussed by: @GenesNDiseases, @genesndiseases.bsky.social

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FDA fast track for sapanisertib plus serabelisib and paclitaxel in PI3K/AKT/mTOR-altered endometrial cancer

Sapanisertib and serabelisib plus paclitaxel received FDA fast track designation for pretreated advanced PI3K/AKT/mTOR pathway-altered endometrial cancer, supported by phase 2 data in this molecularly selected population. The designation targets a pathway that has resisted single-agent approaches, and the combination of dual PI3K/mTOR blockade with a taxane backbone is now the subject of whether this pairing finally makes the pathway clinically tractable in endometrial cancer.

Discussed by: @OncLive, @OncLive

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Racial survival disparities in endometrial cancer: a 159% higher death risk under 65, and unexplained residual disparity in insured patients over 65

Black women less than 65 years old with endometrial cancer have a 159% greater risk for death than white women — a disparity that dwarfs what is seen in older age groups. In insured patients above 65, comorbidities, tumor characteristics, treatment, and socioeconomic status accounted for much of the Black-White survival gap, but some disparity remained unexplained even after adjustment. If measured clinical and socioeconomic factors explain the gap in insured patients over 65 but not in those under 65, the question is where intervention should be targeted in younger patients.

Discussed by: @HemOncToday, @JAMANetworkOpen

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CTNNB1 and PTEN co-mutations drive aggressive endometrial cancer progression

Co-mutations of CTNNB1 and PTEN drive aggressive tumor progression in endometrial cancer, according to work published open access by Shamsun Nahar and colleagues in Disease Models & Mechanisms. The clinical debate is whether CTNNB1/PTEN co-mutation status should be used to escalate adjuvant therapy in otherwise low-risk endometrioid tumors.

Discussed by: @DMM_Journal, @dmmjournal.bsky.social

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🔥 Top Ranked Tweets

Journal of Clinical Oncology @JCO_ASCO

Systemic Treatment of Ovarian Cancer Recurrence: ASCO Living Guideline, Version 2026.1.0

Read the full article. https://t.co/HakOT4v7QQ
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