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Purpose: We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum-refractory epithelial ovarian cancer (PROC)., Patients and Methods: NRG-GY005 is an open-label, four-arm, phase II/III superiority trial enrolling patients with high-grade serous/endometrioid PROC and one to three previous therapies. Key exclusion criteria included previous receipt of poly(ADP-ribose) polymerase inhibitor or receipt of antiangiogenic therapy in the recurrent setting. Treatment arms (SOC [once weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin], cediranib, olaparib, or cediranib/olaparib) were equally randomized. A preplanned interim futility analysis on the basis of progression-free survival (PFS) selected treatment arms to advance to phase III. PFS and overall survival (OS) were phase III coprimary end points, with hierarchical testing of PFS followed by OS to preserve type 1 error control, designed to have 90% power for a 0.625 PFS hazard ratio (HR). OS was tested after PFS in the multiple hierarchical testing procedure. Secondary end points included objective response rate (ORR) and patient-reported outcomes., Results: Five hundred sixty-two eligible patients were enrolled for phase II/III. Three arms met PFS criteria to carry forward to phase III (SOC, cediranib/olaparib, and cediranib). Median PFS was 3.4, 5.2, and 4 months with SOC, cediranib/olaparib, and cediranib, respectively, with a median follow-up duration of 42.2 months. PFS HR estimates for cediranib/olaparib and cediranib ( v SOC) were 0.796 (98.3% CI, 0.597 to 1.060) and 0.972 (98.3% CI, 0.726 to 1.300), respectively. Median OS was 13.6, 12.8, and 10.5 months, and of 443 patients with measurable disease, ORR was 8.6%, 24.7%, and 13.1% for SOC, cediranib/olaparib, and cediranib, respectively. No new safety signals were identified. In patients receiving cediranib/olaparib, no statistically significant difference was observed on the NFOSI-DRS-P subscale compared with SOC (98.3% CI, -1.3 to 1.5, P = .8725)., Conclusion: The cediranib-containing arms demonstrated clinical activity on the basis of PFS but were not superior compared with SOC.

Background: The bag-valve-mask (BVM) or manual resuscitator bag is used as a first-line technique to ventilate patients with respiratory failure. Volume-restricted manual resuscitator bags (eg, pediatric bags) have been suggested to minimize overventilation and associated complications. There are studies that both support and caution against the use of a pediatric resuscitator bag to ventilate an adult patient. In this study, we evaluated the ability of pre-hospital clinicians to adequately ventilate an adult manikin with both an adult- and pediatric-size manual resuscitator bag without the assistance of an advanced airway or airway adjunct device., Methods: This study was conducted at an international conference in 2022. Conference attendees with pre-hospital health care experience were recruited to ventilate an adult manikin using a BVM for 1 min with both an adult and pediatric resuscitator bag, without the use of adjunct airway devices, while 6 ventilatory variables were collected or calculated: tidal volume (V T ), breathing frequency, adequate breaths (V T > 150 mL), proportion of adequate breaths, peak inspiratory pressure (PIP), and estimated alveolar ventilation (EAV)., Results: A total of 208 participants completed the study. Ventilation with the adult-sized BVM delivered an average V T of 290.4 mL compared to 197.1 mL ( P < .001) when using the pediatric BVM. PIP with the adult BVM was higher than with the pediatric BVM (10.6 cm H 2 O vs 8.6 cm H 2 O, P < .001). The median EAV with the adult bag (1,138.1 [interquartile range [IQR] 194.0-2,869.9] mL/min) was markedly greater than with the pediatric BVM (67.7 [IQR 0-467.3] mL/min, P < .001)., Conclusions: Both pediatric- and adult-sized BVM provided lower ventilation volumes than those recommended by professional guidelines for an adult. Ventilation with the pediatric BVM was significantly worse than with the adult bag when ventilating a simulated adult subject., Competing Interests: Dr Slutsky discloses a relationship with SafeBVM Corporation. The remaining authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Objective: Manual ventilation is a basic skill that every emergency medical services (EMS) responder is expected to perform proficiently. Improper manual ventilation may result in significant morbidity; however, there is no feedback mechanism or method of control for the volume, pressure, or frequency during manual ventilation. In this study, we aimed to quantify the volume and peak pressures of manually delivered breaths using a simulated lung., Methods: One hundred ninety-nine volunteer EMS responders from the EMS World Expo 2019 and EMS Today 2020 participated in this study. Each volunteer manually ventilated a simulated lung using a bag-valve-mask (BVM) for 18 breaths. Descriptive statistics were computed for peak pressures (P peak ) and tidal volumes (V T) ), and a multivariable linear regression was conducted to determine whether there was an independent correlation between P peak or V T and seven different variables., Results: Both P peak and V T delivered by EMS responders had a high level of variability; 82.9% of clinicians delivered at least one breath exceeding the recommended safety thresholds; and 98.0% delivered at least one breath that was inadequate or excessive. Our results showed no likely clinical significant role of sex, hand size, frequency of use, or years of experience in determining P peak and V T . Tidal volumes were significantly higher in males ( p  < 0.001), those using two-hand manual ventilation ( p  < 0.001), shorter hand length ( p  = 0.013), higher confidence ( p  < 0.001), and more years of experience ( p  < 0.001). Peak pressures were significantly higher in those using two-hand manual ventilation ( p  < 0.001), wider hand width ( p  = 0.004), higher confidence ( p  < 0.001), less frequent use of the BVM per month ( p  < 0.001), more experience ( p  < 0.001)., Conclusions: Our study demonstrated large variability of V T and P peak within and, to a lesser degree, between clinicians. Of the seven variables that might have affected tidal volume or peak pressures, only the use of two hands versus one hand had a potentially clinically significant effect. Our study identifies a clear need for BVM improvement to ensure every practitioner can deliver breaths at appropriate volumes and safe pressures.

Purpose: To compare taxane maintenance chemotherapy, paclitaxel (P) and paclitaxel poliglumex (PP), with surveillance (S) in women with ovarian, peritoneal, or fallopian tube (O/PC/FT) cancer who attained clinical complete response after first-line platinum-taxane therapy., Methods: Women diagnosed with O/PC/FT cancer who attained clinical complete response after first-line platinum-taxane-based chemotherapy were randomly allocated 1:1:1 to S or maintenance, P 135 mg/m 2 once every 28 days for 12 cycles, or PP at the same dose and schedule. Overall survival (OS) was the primary efficacy end point., Results: Between March 2005 and January 2014, 1,157 individuals were enrolled. Grade 2 or worse GI adverse events were more frequent among those treated with taxane (PP: 20%, P: 27% v S: 11%). Grade 2 or worse neurologic adverse events occurred more often with taxane treatment (PP: 46%, P: 36% v S: 14%). At the fourth scheduled interim analysis, both taxane regimens passed the OS futility boundary and the Data Monitoring Committee approved an early release of results. With a median follow-up of 8.1 years, 653 deaths were reported; none were attributed to the study treatment. Median survival durations were 58.3, 56.8, and 60.0 months for S, P, and PP, respectively. Relative to S, the hazard of death for P was 1.091 (95% CI, 0.911 to 1.31; P = .343) and for PP, it was 1.033 (95% CI, 0.862 to 1.24; P = .725). The median times to first progression or death (PFS) were 13.4, 18.9, and 16.3 months for S, P, and PP, respectively. Hazard ratio = 0.801; 95% CI, 0.684 to 0.938; P = .006 for P and hazard ratio = 0.854; 95% CI, 0.729 to 1.00; P = .055 for PP., Conclusion: Maintenance therapy with P and PP did not improve OS among patients with newly diagnosed O/tubal/peritoneal cancer, but may modestly increase PFS. GI and neurologic toxicities were more frequent in the taxane treatment arms.

Purpose: Platinum-based chemotherapy is the standard of care for platinum-sensitive ovarian cancer, but complications from repeated platinum therapy occur. We assessed the activity of two all-oral nonplatinum alternatives, olaparib or olaparib/cediranib, versus platinum-based chemotherapy., Patients and Methods: NRG-GY004 is an open-label, randomized, phase III trial conducted in the United States and Canada. Eligible patients had high-grade serous or endometrioid platinum-sensitive ovarian cancer. Patients were randomly assigned 1:1:1 to platinum-based chemotherapy, olaparib, or olaparib/cediranib. The primary end point was progression-free survival (PFS) in the intention-to-treat population. Secondary end points included activity within germline BRCA -mutated or wild-type subgroups and patient-reported outcomes (PROs)., Results: Between February 04, 2016, and November 13, 2017, 565 eligible patients were randomly assigned. Median PFS was 10.3 (95% CI, 8.7 to 11.2), 8.2 (95% CI, 6.6 to 8.7), and 10.4 (95% CI, 8.5 to 12.5) months with chemotherapy, olaparib, and olaparib/cediranib, respectively. Olaparib/cediranib did not improve PFS versus chemotherapy (hazard ratio [HR] 0.86; 95% CI, 0.66 to 1.10; P = .077). In women with germline BRCA mutation, the PFS HR versus chemotherapy was 0.55 (95% CI, 0.32 to 0.94) for olaparib/cediranib and 0.63 (95% CI, 0.37 to 1.07) for olaparib. In women without a germline BRCA mutation, the PFS HR versus chemotherapy was 0.97 (95% CI, 0.73 to 1.30) for olaparib/cediranib and 1.41 (95% CI, 1.07 to 1.86) for olaparib. Hematologic adverse events occurred more commonly with chemotherapy; however, nonhematologic adverse events were higher with olaparib/cediranib. In 489 patients evaluable for PROs, patients receiving olaparib/cediranib scored on average 1.1 points worse on the NFOSI-DRS-P subscale (97.5% CI, -2.0 to -0.2, P = .0063) versus chemotherapy; no difference between olaparib and chemotherapy was observed., Conclusion: Combination olaparib/cediranib did not improve PFS compared with chemotherapy and resulted in reduced PROs. Notably, in patients with a germline BRCA mutation, both olaparib and olaparib/cediranib had significant clinical activity., Competing Interests: Joyce F. LiuConsulting or Advisory Role: Tesaro, Mersana, Clovis Oncology, Genentech/Roche, GlaxoSmithKline, Regeneron, AstraZenecaResearch Funding: Genentech/Roche (Inst), AstraZeneca (Inst), Boston Biomedical (Inst), Acetylon Pharmaceuticals (Inst), Bristol Myers Squibb (Inst), Agenus (Inst), CytomX Therapeutics (Inst), Regeneron (Inst), Tesaro (Inst), Clovis Oncology (Inst), Surface Oncology (Inst), 2X Oncology (Inst), Vigeo Therapeutics (Inst), Aravive (Inst), Arch Oncology (Inst)Travel, Accommodations, Expenses: AstraZeneca, MerckUncompensated Relationships: Merck Mark F. BradyConsulting or Advisory Role: Cel-Sci Ursula A. MatulonisHonoraria: Advaxis, Alkermes, SymphogenConsulting or Advisory Role: Merck, Novartis, NextCure, AstraZeneca, Blueprint Medicines, Trillium Therapeutics, GlaxoSmithKline, AgenusResearch Funding: Merck, Novartis, Tesaro, Syndax, Immunogen, Mersana, Leap Therapeutics, Fujifilm, SQZ BiotechTravel, Accommodations, Expenses: AstraZeneca Austin MillerConsulting or Advisory Role: AstraZeneca/Merck, Regeneron (Inst)Uncompensated Relationships: Genetect Elizabeth M. SwisherLeadership: IDEAYA Biosciences David CellaStock and Other Ownership Interests: FACIT.orgConsulting or Advisory Role: AbbVie, GlaxoSmithKline, Pfizer, Astellas Pharma, Novartis, Bristol Myers Squibb, Asahi Kasei, Ipsen, Mei PharmaResearch Funding: Novartis (Inst), Ipsen (Inst), Pfizer (Inst), PledPharma (Inst), Bristol Myers Squibb (Inst), AbbVie (Inst), Regeneron (Inst), Clovis Oncology (Inst) Noelle G. ClovenConsulting or Advisory Role: Toray Industries Carolyn Y. MullerResearch Funding: AstraZeneca (Inst), Genmab (Inst), VBL Therapeutics (Inst), Roche/Genentech (Inst), TapImmune Inc (Inst), Linnaeus Therapeutics (Inst), agenus (Inst), Incyte (Inst), Merck (Inst)Patents, Royalties, Other Intellectual Property: Have a pending patent on the cancer use for R-ketorolac - not yet its own new drug (Inst)Other Relationship: NCI, NCI, Department of Defense Richard G. MooreHonoraria: Fujirebio DiagnosticsConsulting or Advisory Role: Abcodia, Fujirebio DiagnosticsResearch Funding: Angle Steven E. WaggonerConsulting or Advisory Role: Regeneron Melissa A. GellerResearch Funding: Tesaro, Genentech, FATE Therapeutics, Morphotek, Bayer Keiichi FujiwaraHonoraria: Kyowa Hakko Kirin, Zeria Pharmaceutical, Nippon Kayaku, Chugai Pharma, Eisai, Taiho Pharmaceutical, Daiichi Sankyo, Ono Pharmaceutical, TakedaConsulting or Advisory Role: MSD, Taiho Pharmaceutical, Eisai, Takeda, Genmab, NanoCarrierResearch Funding: Eisai (Inst), Kaken Pharmaceutical (Inst), Chugai Pharma (Inst), Immunogen (Inst), Oncotherapeutics (Inst), AstraZeneca (Inst), Zeria Pharmaceutical (Inst), Ono Pharmaceutical (Inst), MSD (Inst), Regeneron (Inst), Merck KGaA (Inst), Ono Pharmaceutical (Inst), Genmab (Inst), Seattle Genetics (Inst)Travel, Accommodations, Expenses: MSD Angeles Alvarez SecordHonoraria: Myriad GeneticsResearch Funding: Tesaro (Inst), AstraZeneca (Inst), Genentech (Inst), Boehringer Ingelheim (Inst), AbbVie (Inst), Merck (Inst), PharmaMar (Inst), Clovis Oncology (Inst), Eisai (Inst), Seattle Genetics (Inst), Immutep (Inst), GlaxoSmithKline (Inst), VBL Therapeutics (Inst), OncoQuest Pharmaceuticals (Inst)Travel, Accommodations, Expenses: GlaxoSmithKlineUncompensated Relationships: Roche/Genentech, VBL Therapeutics, GOG Foundation, OncoQuest Pharmaceuticals, Regeneron, Aravive Katherine M. MoxleyConsulting or Advisory Role: Tessa Therapeutics (Inst), Clovis Oncology (Inst), GlaxoSmithKline Michael A. BookmanEmployment: The Permanente Medical GroupConsulting or Advisory Role: AstraZeneca, AbbVie, Immunogen, Merck Sharp & Dohme, Genentech/Roche, Seattle Genetics, AraviveNo other potential conflicts of interest were reported.

Background: Age and ethnicity are among several factors that influence overall survival (OS) in ovarian cancer. The study objective was to determine whether ethnicity and age were of prognostic significance in women enrolled in a clinical trial evaluating the addition of bevacizumab to front-line therapy., Methods: Women with advanced stage ovarian, primary peritoneal, or fallopian tube cancer were enrolled in a phase III clinical trial. All women had surgical staging and received adjuvant chemotherapy with one of three regimens. Cox proportional hazards models were used to evaluate the relationship between OS with age and race/ethnicity among the study participants., Results: One-thousand-eight-hundred-seventy-three women were enrolled in the study. There were 280 minority women and 328 women over the age of 70. Women age 70 and older had a 34% increase risk for death when compared to women under 60 (HR = 1.34; 95% CI 1.16-1.54). Non-Hispanic Black women had a 54% decreased risk of death with the addition of maintenance bevacizumab (HR = 0.46, 95% CI:0.26-0.83). Women of Asian descent had more hematologic grade 3 or greater adverse events and a 27% decrease risk of death when compared to non-Hispanic Whites (HR = 0.73; 95% CI: 0.59-0.90)., Conclusions: Non-Hispanic Black women showed a decreased risk of death with the addition of bevacizumab and patients of Asian ancestry had a lower death rate than all other minority groups, but despite these clinically meaningful improvements there was no statistically significant difference in OS among the groups., (Copyright © 2021. Published by Elsevier Inc.)