5551 Background: The phase 3 PRIMA trial (NCT02655016) demonstrated that niraparib 1L maintenance therapy significantly extended progression-free survival (PFS) compared with placebo in patients with newly diagnosed aOC that responded to 1L platinum-based chemotherapy. Using data from the Nov 2019 cutoff (median follow-up, ≈1.7 y), pooled results from both treatment arms found that disease progression negatively affected HRQOL. Here we report updated HRQOL results from the PRIMA final analysis. Methods: In PRIMA, patients were randomized 2:1 to niraparib or placebo 1L maintenance once daily. HRQOL was assessed as a prespecified secondary endpoint using patient-reported responses to multiple instruments, including the European Organisation for Research and Treatment of Cancer QOL Core Questionnaire (EORTC QLQ-C30) and the EORTC QLQ Ovarian Cancer Module (EORTC QLQ-OV28). Assessments were collected at baseline, at designated intervals while on study treatment; at the end of treatment (EOT); and at 4, 8, 12, and 24 weeks after the last dose of study treatment. Post hoc analysis results are reported herein (clinical cutoff: Apr 8, 2024; median follow-up, 6.2 y). Results: In the overall population (niraparib, n=487; placebo, n=246), EOT survey completion rates exceeded 80% across both instruments. In both treatment arms, disease progression significantly reduced overall HRQOL per the EORTC QLQ-C30, with marked decreases from the last on-treatment visit (LOTV) for global health status/QOL that never recovered to LOTV levels (Table). Disease progression was also associated with deterioration across all 5 functional scales of the EORTC QLQ-C30 and worsening symptoms of fatigue, nausea/vomiting, pain, dyspnea, appetite loss, diarrhea, and financial difficulties. On the EORTC QLQ-OV28, progression was associated with decreased scores for body image, sexuality, and attitude toward disease/treatment functional scales and worsening abdominal/gastrointestinal symptoms. Conclusions: Disease progression negatively impacted HRQOL across treatment arms in PRIMA. These results support PFS as a clinically relevant endpoint in patients with aOC, as delays in disease progression help preserve HRQOL. Clinical trial information: NCT02655016 . LS mean change from LOTV (95% CI) Niraparib(n=487) Placebo(n=246) EORTC QLQ-C30 global health status/QOL EOT –8.6 (–10.9, –6.4) –7.4 (–10.1, –4.7) Week 4 post EOT –10.0 (–12.7, –7.3) –10.7 (–14.0, –7.4) Week 8 post EOT –10.1 (–12.9, –7.2) –12.2 (–16.0, –8.5) Week 12 post EOT –11.5 (–14.0, –9.1) –9.5 (–12.6, –6.3) Week 24 post EOT –10.7 (–13.4, –8.1) –9.6 (–13.1, –6.2) EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer QOL Core Questionnaire; EOT, end of treatment; LOTV, last on-treatment visit; LS, least squares; QOL, quality of life.

PURPOSE The interleukin-6/Janus kinase (JAK)/signal transducers and activators of transcription 3 axis is a reported driver of chemotherapy resistance. We hypothesized that adding the JAK1/2 inhibitor ruxolitinib to standard chemotherapy would be tolerable and improve progression-free survival (PFS) in patients with ovarian cancer in the upfront setting. MATERIALS AND METHODS Patients with ovarian/fallopian tube/primary peritoneal carcinoma recommended for neoadjuvant chemotherapy were eligible. In phase I, treatment was initiated with dose-dense paclitaxel (P) 70 mg/m2 once daily on days 1, 8, and 15; carboplatin AUC 5 intravenously day 1; and ruxolitinib 15 mg orally (PO) twice a day, every 21 days (dose level 1). Interval debulking surgery (IDS) was required after cycle 3. Patients then received three additional cycles of chemotherapy/ruxolitinib, followed by maintenance ruxolitinib. In the randomized phase II, patients were randomly assigned to paclitaxel/carboplatin with or without ruxolitinib at 15 mg PO twice a day for three cycles, IDS, followed by another three cycles of chemotherapy/ruxolitinib, without further maintenance ruxolitinib. The primary phase II end point was PFS. RESULTS Seventeen patients were enrolled in phase I. The maximum tolerated dose and recommended phase II dose were established to be dose level 1. One hundred thirty patients were enrolled in phase II with a median follow-up of 24 months. The regimen was well tolerated, with a trend toward higher grade 3 to 4 anemia (64% v 27%), grade 3 to 4 neutropenia (53% v 37%), and thromboembolic events (12.6% v 2.4%) in the experimental arm. In the randomized phase II, the median PFS in the reference arm was 11.6 versus 14.6 in the experimental, hazard ratio (HR) for PFS was 0.702 (log-rank P = .059). The overall survival HR was 0.785 ( P = .24). CONCLUSION Ruxolitinib 15 mg PO twice a day was well tolerated with acceptable toxicity in combination with paclitaxel/carboplatin chemotherapy. The primary end point of prolongation of PFS was achieved in the experimental arm, warranting further investigation.

Objective. To assess patient -reported health -related quality of life (HRQoL) in patients with ovarian cancer (OC) who received niraparib as first -line maintenance therapy. Methods. PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) enrolled patients with newly diagnosed advanced OC who responded to first -line platinum -based chemotherapy. Patients were randomized (2:1) to niraparib or placebo once daily in 28 -day cycles until disease progression, intolerable toxicity, or death. HRQoL was assessed as a prespecified secondary end point using patient -reported responses to the European Organisation for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30), the EORTC QLQ Ovarian Cancer Module (EORTC QLQ-OV28), the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), and EQ-5D-5L questionnaires. Assessments were collected at baseline and every 8 weeks (+/- 7 days) for 56 weeks, beginning on cycle 1/day 1, then every 12 weeks (+/- 7 days) thereafter while the patient received study treatment. Results. Among trial participants (niraparib, n = 487; placebo, n = 246), PRO adherence exceeded 80% for all instruments across all cycles. Patients reported no decline over time in HRQoL measured via EORTC QLQ-C30 Global Health Status/QoL and FOSI overall scores. Scores for abdominal/gastrointestinal symptoms (EORTC QLQ-OV28) and nausea and vomiting, appetite loss, and constipation (EORTC QLQ-C30) were higher (worse symptoms) in niraparib-treated patients than placebo -treated patients; except for constipation, these differences resolved over time. Patients did not self -report any worsening from baseline of fatigue, headache, insomnia, or abdominal pain on questionnaires. Conclusions. Despite some early, largely transient increases in gastrointestinal symptoms, patients with OC treated with niraparib first -line maintenance therapy reported no worsening in overall HRQoL. (c) 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Table of non-BRCA mutations with clinical characteristics

3-way interaction analyses between outcome, treatment, and markers.

Quartile analysis of IL6. Median survival times are given in months, and HR's represent treatment hazard ratios.

Flow diagram of patients through the study.

Upitifamab Rilsodotin (UpRi) is a first-in-class NaPi2b-targeting Antibody Drug Conjugate (ADC) with a novel scaffold-linker-payload that enables a high drug-to-antibody ratio and controlled bystander effect. NaPi2b is a sodium-dependent phosphate transporter protein broadly expressed in high-grade serous ovarian cancer (HGSOC) with limited expression in healthy tissues. It is estimated that about two-thirds of HGSOC patients are NaPi2b-positive. Studies are being conducted to evaluate UpRi safety and efficacy in platinum-resistant ovarian cancer (PROC), but there remains an unmet need in the maintenance setting for patients with platinum-sensitive recurrent ovarian cancer (PSOC), particularly patients with stable disease, those who have progressed on PARP inhibitors, and those who received standard of care platinum-based treatment and are at high risk of early relapse.

TPS5613 Background: UpRi is a first in class NaPi2b ADC with a novel scaffold-linker-payload that is designed to enable high drug-to-antibody ratio and controlled bystander effect. NaPi2b is a sodium-dependent phosphate transporter protein broadly expressed in HGSOC, with limited expression in healthy tissues. Interim data from a previous phase 1b study of heavily pretreated HGSOC patients reported clinical activity and tolerability data for UpRi as a monotherapy, most notably in patients with NaPi2b positive tumors (TPS≥75). Based on these emerging single-agent safety and efficacy data, it is hypothesized that UpRi in combination with carboplatin may provide additional clinical benefit for patients in earlier lines of treatment. UPGRADE-A is a Phase 1 dose escalation (DES) and expansion (EXP) study to evaluate UpRi and carboplatin followed by UpRi maintenance in recurrent platinum-sensitive HGSOC. The DES portion of UPGRADE-A has completed enrollment, and the EXP portion is ongoing. Methods: The EXP cohort of UPGRADE-A is enrolling patients with recurrent or metastatic PSOC (defined as having achieved a PR or CR to 4+ cycles in their last platinum containing regimen) who have received 1-3 prior lines of therapy. Up to 1 non-platinum based prior chemotherapy regimen is allowed, provided it is not the most recent line of chemotherapy. The primary objective of EXP is feasibility of UpRi + carboplatin at the RP2D, defined as 60% of patients completing at least 4 cycles of UpRi + carboplatin without discontinuing treatment early for reasons other than disease progression. Secondary objectives include the safety/tolerability, pharmacokinetics, and preliminary anti-neoplastic activity of the UpRi + carboplatin combination. Tumor tissue must be provided (archival or fresh sample) for retrospective NaPi2b assessment. UpRi 30mg/m2 + carboplatin (AUC 5) will be administered IV every 28 days for up to 6 cycles, followed by UpRi maintenance monotherapy until disease progression or unacceptable toxicity. Up to 30 patients are expected to enroll in EXP, and the trial is currently open for enrollment. NCT04907968. Clinical trial information: NCT04907968 .

The objectives of our study were to define long-term outcomes and determine factors that impact the duration of response to levonorgestrel intrauterine device (LIUD) as a non-surgical treatment option for atypical hyperplasia (AH) and grade 1 (g1) endometrioid endometrial cancer (EEC).

Relationship between covariates and IL6.

Association between outcomes (PFS and OS) and baseline covariates (age, stage/debulking status, and performance status).

Survival by mutation type, and mutation data by the source of sequenced DNA

PURPOSE:In randomized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer. Although in nonrandomized trials, carboplatin and paclitaxel was a less toxic and highly active combination regimen, there remained concern regarding its efficacy in patients with small-volume, resected, stage III disease. Thus, we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population. PATIENTS AND METHODS:Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were randomly assigned to receive cisplatin 75 mg/m2 plus a 24-hour infusion of paclitaxel 135 mg/m2 (arm I), or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m2 over 3 hours (arm II). RESULTS:Seven hundred ninety-two eligible patients were enrolled onto the study. Prognostic factors were similar in the two treatment groups. Gastrointestinal, renal, and metabolic toxicity, as well as grade 4 leukopenia, were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II. Neurologic toxicity was similar in both regimens. Median progression-free survival and overall survival were 19.4 and 48.7 months, respectively, for arm I compared with 20.7 and 57.4 months, respectively, for arm II. The relative risk (RR) of progression for the carboplatin plus paclitaxel group was 0.88 (95% confidence interval [CI], 0.75 to 1.03) and the RR of death was 0.84 (95% CI, 0.70 to 1.02). CONCLUSION:In patients with advanced ovarian cancer, a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity, is easier to administer, and is not inferior, when compared with cisplatin plus paclitaxel.

TPS5614 Background: UpRi is a first-in-class NaPi2b-targeting ADC with a novel scaffold-linker-payload that enables high drug-to-antibody ratio and controlled bystander effect. NaPi2b is a sodium-dependent phosphate transporter protein broadly expressed in high-grade serous ovarian cancer (HGSOC) with limited expression in healthy tissues. It is estimated that the majority of HGSOCs have high NaPi2b expression. Studies are being conducted to evaluate UpRi safety and efficacy in platinum-resistant ovarian cancer (PROC), but there remains an unmet need in the maintenance setting for patients with recurrent platinum-sensitive ovarian cancer (PSOC), particularly for patients who have received prior maintenance therapy, are at high-risk of early relapse, and where close monitoring after platinum-based therapy would generally be considered preferable. Methods: UP-NEXT is a Phase 3 study evaluating UpRi monotherapy as post-platinum maintenance treatment in recurrent PSOC, enrolling patients with NaPi2b-positive tumors (defined as TPS ≥75). Patients must have received 2-4 prior lines of platinum containing chemotherapy, achieved a partial or complete response in their penultimate platinum regimen, and progressed >6 months after completion of the last dose of platinum in the penultimate regimen. Patients may be enrolled if their best response to the last line of treatment is no evidence of disease, complete or partial response, or stable disease. Prior PARPi treatment is required for patients with a BRCA mutation. Patients who received bevacizumab in combination with their most recent platinum containing regimen are excluded. Patients are randomized 2:1 to UpRi 30mg/m2 or placebo, given IV Q4W. The primary endpoint is PFS assessed by BICR, with key secondary endpoint of OS. UP-NEXT is conducted in collaboration with GOG(3049) and ENGOT(Ov71-NSGO-CTU). Approximately 350 patients will be enrolled globally. NCT05329545. Clinical trial information: NCT05329545 .

The medians and ranges for all analytes at baseline.