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Background: The PRIMA/ENGOT‐OV26/GOG‐3012 (NCT02655016) trial was amended to prospectively evaluate the safety and efficacy of an individualized starting dose (ISD) regimen of niraparib for first‐line maintenance therapy in patients with newly diagnosed advanced ovarian cancer. Methods: In the phase 3 PRIMA trial, patients with newly diagnosed advanced ovarian cancer with a complete/partial response to first‐line platinum‐based chemotherapy (N = 733) were initially treated with a fixed starting dose (FSD) regimen of 300 mg once daily. Subsequently, the protocol was amended so newly enrolled patients received an ISD: 200 mg once daily in patients with baseline body weight < 77 kg or baseline platelet count < 150,000/µL, and 300 mg once daily in all other patients. Efficacy and safety outcomes were assessed by starting dose. Results: Overall, 475 (64.8%) patients were assigned to an FSD (niraparib, n = 317; placebo, n = 158) and 258 (35.2%) were assigned to an ISD (niraparib, n = 170; placebo, n = 88). Efficacy in patients who received FSD or ISD was similar for the overall (FSD hazard ratio [HR], 0.59 [95% CI, 0.46–0.76] vs. ISD HR, 0.69 [95% CI, 0.48–0.98]) and the homologous recombination–deficient (FSD HR, 0.44 [95% CI, 0.30–0.64] vs. ISD HR, 0.39 [95% CI, 0.22–0.72]) populations. In patients with low body weight/platelet count, rates of grades ≥3 and 4 hematologic treatment‐emergent adverse events, dose interruptions, and dose reductions were lower for those who received ISD than for those who received FSD. Conclusions: In PRIMA, similar dose intensity, similar efficacy, and improved safety were observed with the ISD compared with the FSD regimen. Results from the phase 3 PRIMA trial of niraparib first‐line maintenance therapy that prospectively evaluated fixed versus individualized dosing support the selection of a niraparib starting dose based on an individual's body weight and platelet count. In prespecified analyses, patients who received the individualized starting dose of niraparib experienced similar progression‐free survival and improved safety outcomes compared with patients who received the fixed starting dose of niraparib. [ABSTRACT FROM AUTHOR]

Among the pharmaceutical options available for treatment of ovarian cancer, increasing attention has been progressively focused on pegylated liposomal doxorubicin (PLD), whose unique formulation prolongs the persistence of the drug in the circulation and potentiates intratumor accumulation. Pegylated liposomal doxorubicin (PLD) has become a major component in the routine management of epithelial ovarian cancer. In 1999 it was first approved for platinum-refractory ovarian cancer and then received full approval for platinum-sensitive recurrent disease in 2005. PLD remains an important therapeutic tool in the management of recurrent ovarian cancer in 2012. Recent interest in PLD/carboplatin combination therapy has been the object of phase III trials in platinum-sensitive and chemonaıve ovarian cancer patients reporting response rates, progressive-free survival, and overall survival similar to other platinum-based combinations, butwith amore favorable toxicity profile and convenient dosing schedule. This paper summarizes data clarifying the role of pegylated liposomal doxorubicin (PLD) in ovarian cancer, as well as researches focusing on adding novel targeted drugs to this cytotoxic agent. [ABSTRACT FROM AUTHOR]

To report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53 wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy. Analysis of the prespecified, exploratory subgroup of patients with TP53 wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53 wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed. Of the 263 patients enrolled in the SIENDO trial, 113 patients had TP53 wt EC; 70/113 (61.9%) had TP53 wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53 wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53 wt patients who received selinexor compared with placebo was 28.4 versus 5.2 months (36.8-month follow-up, HR 0.44; 95% CI 0.27–0.73). A benefit in mPFS was seen with selinexor versus placebo regardless of MMR status (patients with TP53 wt/pMMR EC: 39.5 vs 4.9 months, HR 0.36; 95% CI 0.19–0.71; patients with TP53 wt/dMMR EC: 13.1 vs 3.7 months, HR 0.49; 95% CI 0.18–1.34). Selinexor treatment was generally manageable, with no new safety signals identified. In the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53 wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931). [Display omitted] • Patients with TP53 wild-type (wt) advanced or recurrent endometrial cancer have limited effective treatment options. • Selinexor is an oral exportin 1 (XPO1) inhibitor activating p53 through nuclear retention of key tumor suppressor proteins. • Meaningful increase in median progression-free survival (mPFS) of TP53 wt were seen with selinexor maintenance therapy. • Increase in mPFS with selinexor in TP53 wt subgroup was observed regardless of mismatch repair status. • Selinexor was generally manageable, with no new safety signals observed. [ABSTRACT FROM AUTHOR]

This open-label phase II clinical trial evaluated the antitumor activity and safety of trabectedin in patients with advanced ovarian (OC) or uterine carcinosarcomas (UC). Eligible patients were adults (≥18 years) with histologically proven recurrent OC/UC not amenable to surgery or radiotherapy who received up to two prior chemotherapy lines. Trabectedin 1.3 mg/m2 was administered as a 3-h infusion every three weeks. The primary endpoint was objective response rate (ORR) as per RECIST v.1.1. If at least 8 of 43 patients (18.6%) achieve an objective response, trabectedin would be declared worthy for further investigations. Forty-five patients with either OC (n = 32) or UC (n = 13) from seven MITO centers across Italy were enrolled. The ORR was 11.9% (90% CI: 6–23) and included two patients with a complete response and three with a partial response. Eight patients (19.0%) had disease stabilization for a disease control rate of 31.0% (90% CI: 20–44). Median progression-free survival was 2.01 months (95% CI: 1.78–2.30) and median overall survival was 4.64 months (95% CI: 3.19–8.29). Neutrophil count decreases (n = 8, 18.2%) and transaminase increases (n = 6, 13.6%) were the most common grade 3–5 adverse events related with trabectedin. Two patients died due to trabectedin-related grade 5 hematological toxicity. Although trabectedin did not meet the prespecified activity criteria, it confers modest but clinically meaningful benefit to patients with advanced OC/UC as being as effective as any other available treatment for this indication. The toxicity profile appears in line with that previously reported for the drug. • Trabectedin did not meet the prespecified activity criteria to be considered worthy for further investigations in OC or UC. • Yet, in heavily pre-treated patients trabectedin elicited modest clinical benefit comparable with other available drugs. • Trabectedin was well tolerated, with a safety profile consistent with previous experiences. [ABSTRACT FROM AUTHOR]

Background Analysis of progression-free survival (PFS) as the primary endpoint in advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer (AEOC) trials may be confounded by the difficulty of radiologic evaluation of disease progression and the potential for discrepancy between investigator and blinded independent central assessments. PFS as assessed by local investigator (INV) was the primary endpoint of AGO-OVAR16, a randomized, double-blind trial of pazopanib maintenance therapy in AEOC. To confirm the robustness of the primary analysis, PFS was also evaluated by blinded independent central review (BICR). Methods Patients with histologically confirmed AEOC (N = 940) were randomized 1:1 to receive pazopanib 800 mg/day or placebo for up to 24 months. Tumor response in the intent-to-treat population was evaluated by CT/MRI every 6 months and analyzed per RECIST 1.0. Results Pazopanib prolonged PFS versus placebo by INV (median 17.9 vs 12.3 months; hazard ratio [HR] = 0.766, 95% confidence interval [CI]: 0.643-0.911; P = 0.0021). Results for PFS by BICR were similar (median 15.4 vs 11.8 months; HR = 0.802, 95% CI: 0.678-0.949; P = 0.0084). Progression events were recorded later by INV in 23% of pazopanib-treated patients and 17% of placebo-treated patients. The overall concordance between INV and BICR assessments was 84% and 86% in the pazopanib and placebo arms, respectively. Conclusions By INV and BICR assessments, maintenance therapy with pazopanib in AEOC provided a significantly longer PFS than placebo. The good overall concordance between INV and BICR assessments, as well as HR and P value consistency, supports the reliability of investigator-assessed PFS as the primary endpoint in AGO-OVAR16. [ABSTRACT FROM AUTHOR]