Tolerability of the niraparib individualized starting dose in the PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib first-line maintenance therapy.

PURPOSE: To explore safety and tolerability parameters for the niraparib individualized starting dose (ISD) in patients with newly diagnosed advanced ovarian cancer that responded to platinum-based chemotherapy who participated in the phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial (NCT02655016). METHODS: The PRIMA protocol was amended so newly enrolled patients received an ISD based on baseline body weight/platelet count. In this ad hoc analysis, the timing, duration, and resolution of the first occurrence of common any-grade hematologic (thrombocytopenia, anemia, neutropenia) and nonhematologic (nausea, asthenia/fatigue, constipation, insomnia, hypertension) treatment-emergent adverse events (TEAEs) were evaluated by treatment arm in the ISD safety population (data cutoff, November 17, 2021; median follow-up, 3.5 years). RESULTS: Of 733 randomized patients, 255 were enrolled after the ISD protocol amendment and received ≥ 1 dose of study treatment (niraparib, 169; placebo, 86). In the niraparib arm, median times to first events were 22.0-35.0 days for hematologic TEAEs and 7.0-56.0 days for nonhematologic TEAEs. First events resolved in ≥ 89.8% of patients for hematologic TEAEs; for nonhematologic TEAEs, resolution rates ranged from 55.3% (insomnia) to 86.0% (nausea). Median durations of first hematologic TEAEs were ≤ 16.0 days, but for first nonhematologic TEAEs ranged from 18.0 days (nausea) to 134.0 days (insomnia). CONCLUSION: The niraparib ISD was generally well tolerated and TEAEs were manageable. Common hematologic and nonhematologic TEAEs occurred early and first events of hematologic TEAEs had a short duration (≈ 2 weeks) and a high resolution rate. These findings support close monitoring immediately following niraparib initiation and may help inform patient expectations for niraparib safety.

A phase III, multicenter, randomized study of olvimulogene nanivacirepvec followed by platinum-doublet chemotherapy and bevacizumab compared with platinum-doublet chemotherapy and bevacizumab in women with platinum-resistant/refractory ovarian cancer.

BACKGROUND: Treatment options for patients with platinum-resistant/refractory ovarian cancers are limited and only marginally effective. The development of novel, more effective therapies addresses a critical unmet medical need. Olvimulogene nanivacirepvec (Olvi-Vec), with its strong immune modulating effect on the tumor microenvironment, may provide re-sensitization to platinum and clinically reverse platinum resistance or refractoriness in platinum-resistant/refractory ovarian cancer. PRIMARY OBJECTIVE: The primary objective is to evaluate the efficacy of intra-peritoneal Olvi-Vec followed by platinum-based chemotherapy and bevacizumab in patients with platinum-resistant/refractory ovarian cancer. STUDY HYPOTHESIS: This phase III study investigates Olvi-Vec oncolytic immunotherapy followed by platinum-based chemotherapy and bevacizumab as an immunochemotherapy evaluating the hypothesis that such sequential combination therapy will prolong progression-free survival (PFS) and bring other clinical benefits compared with treatment with platinum-based chemotherapy and bevacizumab. TRIAL DESIGN: This is a multicenter, prospective, randomized, and active-controlled phase III trial. Patients will be randomized 2:1 into the experimental arm treated with Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab or the control arm treated with platinum-doublet chemotherapy and bevacizumab. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have recurrent, platinum-resistant/refractory, non-resectable high-grade serous, endometrioid, or clear-cell ovarian, fallopian tube, or primary peritoneal cancer. Patients must have had ≥3 lines of prior chemotherapy. PRIMARY ENDPOINT: The primary endpoint is PFS in the intention-to-treat population. SAMPLE SIZE: Approximately 186 patients (approximately 124 patients randomized to the experimental arm and 62 to the control arm) will be enrolled to capture 127 PFS events. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Expected complete accrual in 2024 with presentation of primary endpoint results in 2025. TRIAL REGISTRATION: NCT05281471.

Phase III randomized trial of second-line ixabepilone versus paclitaxel or doxorubicin in women with advanced endometrial cancer.

OBJECTIVE: The purpose of this multicenter, open label, randomized phase III study was to determine whether ixabepilone resulted in improved overall survival (OS) compared with commonly used single-agent chemotherapy (doxorubicin or paclitaxel) in women with locally advanced, recurrent, or metastatic endometrial cancer with at least one failed prior platinum-based chemotherapeutic regimen. METHODS: Patients were randomized 1:1 to ixabepilone (40mg/m(2)), or either paclitaxel (175mg/m(2)) or doxorubicin (60mg/m(2)), every 21days. Patients that had previously received an anthracycline were randomized to ixabepilone or paclitaxel; all other patients were randomized to ixabepilone or doxorubicin. An interim analysis of futility for OS was planned. RESULTS: At the time of database lock, 496 patients were randomized to receive ixabepilone (n=248) or control (n=248); nine patients in the control arm were not treated. The interim analysis of futility for OS (219 events) favored the control chemotherapy arm (hazard ratio=1.3 [95% confidence interval: 1.0-1.7], stratified log rank test P=0.0397), indicating that the study would not meet its primary objective. The study was discontinued based on the interim OS results. The frequency of adverse events was comparable between the treatment arms. CONCLUSIONS: The study did not meet its primary objective of improving OS in the ixabepilone arm compared to the control chemotherapy arm. A favorable risk/benefit ratio was not observed for ixabepilone versus control at the time of the interim analysis. The safety results were consistent with the known safety profiles of ixabepilone and control.

Comparison of robotic, laparoscopic, and abdominal myomectomy in a community hospital.

BACKGROUND AND OBJECTIVES: To evaluate the operative outcomes between robotic, laparoscopic, and abdominal myomectomies performed by a private gynecologic oncology practice in a suburban community hospital. METHODS: The medical records of 322 consecutive robotic, laparoscopic, and abdominal myomectomies performed from January 2007 through December 2009 were reviewed. The outcomes were collected from a retrospective review of patient medical records. RESULTS: Records for 14/322 (4.3%) patients were incomplete. Complete data were available for 308 patients, including 169 (54.9%) abdominal, 73 (23.7%) laparoscopic, and 66 (21.4%) robotic-assisted laparoscopic myomectomies. Patients were similar in age, body mass index, parity, and previous abdominopelvic surgery. Median operative time for robotic surgery (140 min) was significantly longer (P<.005) compared to laparoscopic (70 min) and abdominal (72 min) myomectomies. Robotic and laparoscopic myomectomies had significantly less estimated blood loss and hospital stay compared to abdominal myomectomies. There was no significant difference in complications or in the median size of the largest myoma removed between the different modalities. However, the median aggregate weight of myomas removed abdominally (200g; range, 1.4 to 2682) was significantly larger than that seen laparoscopically (115g; range, 1 to 602) and robotically (129g; range 9.4 to 935). Postoperative transfusion was significantly less frequent in robotic myomectomies compared to laparoscopic and abdominal myomectomies. CONCLUSION: While robotic-assisted laparoscopic myomectomies had longer operative times, laparoscopic and robotic assisted laparoscopic myomectomies demonstrated shorter hospital stays, less blood loss, and fewer transfusions than abdominal myomectomies. Robotic myomectomy offers a minimally invasive alternative for management of symptomatic myoma in a community hospital setting.

Early changes in CA125 after treatment with pegylated liposomal doxorubicin or topotecan do not always reflect best response in recurrent ovarian cancer patients.

PURPOSE: To examine early changes in CA125 relative to objective response in patients with recurrent ovarian cancer treated with pegylated liposomal doxorubicin (PLD) or topotecan and to compare the CA125 trends between the two chemotherapeutics. PATIENTS AND METHODS: Patients with recurrent ovarian cancer, all of whom had measurable or evaluable disease, were randomized to receive 50 mg/m2 PLD every 28 days (n = 239) or 1.5 mg/m2 topotecan for 5 days every 21 days (n = 235) as part of a previously reported multicenter study. CA125 measurements were obtained prior to therapy and with each cycle of administration. Assessable patients underwent radiographic evaluation for response after two cycles of therapy. Objective responses were compared to trends in CA125 values at the end of cycles 1 and 2. CA125 changes were categorized as baseline (+/-10%), +/- 10%-25% variance, and > 25% variance. RESULTS: Among patients treated with PLD, 50% of complete responders (CR) and 41% of partial responders (PR) had increases in CA125 from baseline to cycle 1. Increases in CA125 were also seen in topotecan-treated patients; however, fewer patients had increases (20% and 8%, respectively). Overall, 15% of responding patients (CR + PR) receiving PLD and 6% receiving topotecan had elevated CA125 after two cycles of therapy. For those patients achieving a partial response, 19% of PLD-treated patients and 8% of topotecan-treated patients had CA125 levels above baseline at cycle 2. CONCLUSIONS: Considerable intrapatient variation in CA125 values is present among responding patients. Early increases in CA125 may not predict ultimate outcome, especially in PLD-treated patients.

Continuous abdominal fascial closure: a randomized controlled trial of poly(L-lactide/glycolide).

OBJECTIVE: The objective was to compare the handling characteristics and

Visible-regime polarimetric imager: a fully polarimetric, real-time imaging system.

A fully polarimetric optical camera system has been constructed to obtain polarimetric information simultaneously from four synchronized charge-coupled device imagers at video frame rates of 60 Hz and a resolution of 640 x 480 pixels. The imagers view the same scene along the same optical axis by means of a four-way beam-splitting prism similar to ones used for multiple-imager, common-aperture color TV cameras. Appropriate polarizing filters in front of each imager provide the polarimetric information. Mueller matrix analysis of the polarimetric response of the prism, analyzing filters, and imagers is applied to the detected intensities in each imager as a function of the applied state of polarization over a wide range of linear and circular polarization combinations to obtain an average polarimetric calibration consistent to approximately 2%. Higher accuracies can be obtained by improvement of the polarimetric modeling of the splitting prism and by implementation of a pixel-by-pixel calibration.

Asymptomatic postmenopausal simple ovarian cyst.

UNLABELLED: High-resolution transvaginal ultrasound frequently reveals incidental, simple ovarian cysts in asymptomatic postmenopausal women. Traditionally oophorectomy has been recommended for these women. However, evidence is emerging that most postmenopausal simple ovarian cysts are benign, allowing conservative management. Furthermore, many of these cysts will resolve spontaneously. Cancer antigen 125 (CA-125) and color Doppler may help differentiate benign from malignant cysts. When oophorectomy is favored, the laparoscopic approach may be considered, depending on the clinical situation. Nonoperative management of simple ovarian cysts in asymptomatic women is reasonable; regular follow-up with sonography should be performed. Because sonography is an operator-dependent test, it is imperative that the sonographer have expertise in ovarian imaging. Monitoring of CA-125 levels may be useful. Indications for removal during follow-up are increasing size, development of solid components, abnormal Doppler flow, CA-125 elevation, patient desire for removal of the cyst, and noncompliance with sonographic follow-up. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to estimate the prevalence of benign simple ovarian cysts in a postmenopausal population of women, to describe the natural history of a simple ovarian cyst, and outline the features consistent with a benign ovarian cyst on ultrasound.

Benefits and costs of using HPV testing to screen for cervical cancer.

CONTEXT: Despite quality assurance standards, Papanicolaou (Pap) test characteristics remain less than optimal. OBJECTIVE: To compare the societal costs and benefits of human papillomavirus (HPV) testing, Pap testing, and their combination to screen for cervical cancer. DESIGN, SETTING, AND POPULATION: A simulation model of neoplasia natural history was used to estimate the societal costs and quality-adjusted life expectancy associated with 18 different general population screening strategies: Pap plus HPV testing, Pap testing alone, and HPV testing alone every 2 or 3 years among hypothetical longitudinal cohorts of US women beginning at age 20 years and continuing to 65 years, 75 years, or death. MAIN OUTCOME MEASURE: Discounted costs per quality-adjusted life-year (QALY) saved of each screening strategy. RESULTS: Maximal savings in lives were achieved by screening every 2 years until death with combined HPV and Pap testing at an incremental cost of $76 183 per QALY compared with Pap testing alone every 2 years. Stopping biennial screening with HPV and Pap testing at age 75 years captures 97.8% of the benefits of lifetime screening at a cost of $70 347 per QALY. Combined biennial HPV and Pap testing to age 65 years captures 86.6% of the benefits achievable by continuing to screen until age 75 years. Human papillomavirus screening alone was equally effective as Pap testing alone at any given screening interval or age of screening cessation but was more costly and therefore was dominated. In sensitivity analyses, HPV testing would be more effective and less costly than Pap testing at a cost threshold of $5 for an HPV test. CONCLUSIONS: Screening with HPV plus Pap tests every 2 years appears to save additional years of life at reasonable costs compared with Pap testing alone. Applying age limits to screening is a viable option to maintain benefits while reducing costs.