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PURPOSE: To report the results of OPAL (ClinicalTrials.gov identifier: NCT03574779) cohort A, a single-arm substudy of niraparib plus dostarlimab and bevacizumab for the treatment of advanced, platinum-resistant ovarian cancer (PROC). METHODS: Participants with PROC who received 1-2 previous lines of therapy were treated with niraparib (200 or 300 mg once daily), dostarlimab (500 mg once every 3 weeks for four 21-day cycles, followed by 1,000 mg once every 6 weeks), and bevacizumab (15 mg/kg once every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1. Safety was also assessed. Exploratory biomarker end points included evaluation of changes in the tumor molecular profile and microenvironment using baseline and on-treatment tumor samples. RESULTS: Of 41 enrolled participants (median age, 66.0 years [range, 37-83 years]), 9.8% had tumors that were BRCA-mutated, 19.5% were homologous recombination (HR)-deficient, and 17.1% were HR repair (HRR)-mutated. As of the cutoff date, all participants discontinued treatment. The ORR was 17.1% (80% CI, 9.8 to 27.0), including one complete response (2.4%); the disease control rate was 73.2% (80% CI, 62.3 to 82.2). Two participants withdrew before first postbaseline scan because of adverse events (AEs). Grade ≥3 treatment-emergent AEs were reported in 92.7% of participants, with the most common being hypertension (26.8%). Response was not correlated with BRCA, HRR, HR deficiency (HRD), or PD-L1 status. Changes suggesting immune activation were observed in on-treatment samples after triplet therapy. CONCLUSION: Results demonstrated modest activity of niraparib, dostarlimab, and bevacizumab in participants with PROC, many of whom had prognostic factors for poor treatment response. Most participants with response were bevacizumab-naïve. No association was found with HRD, BRCA, or PD-L1 status. AEs were consistent with previous monotherapy reports, except that hypertension was reported more frequently.

IntroductionWe evaluated real-world outcomes in patients with advanced ovarian cancer (AOC) based on their cumulative risk profile and maintenance therapy (MT) status following first-line (1L) treatment.MethodsThis retrospective observational study of a nationwide electronic health record-derived de-identified database included adult patients diagnosed with stage III/IV OC from January 1, 2011 to February 28, 2021, who received 1L therapy and had ≥ 12 weeks of follow-up after the index date (end of 1L therapy). Patients were grouped according to whether they received MT or active surveillance (AS) following 1L treatment and by the cumulative number of risk factors (RF) present (stage IV disease; no surgery/treated with neoadjuvant therapy and interval debulking surgery; had postoperative visible residual disease; and had BRCA wild-type disease/unknown BRCA status). Time to next treatment (TTNT) and overall survival (OS) were assessed with a cloning and inverse probability of censoring (IPC)-weighted Kaplan-Meier method.ResultsAmong 1920 patients, 22.2% received MT and 77.8% received AS. Median IPC-weighted TTNT and OS were 13.3 months (95% CI 11.7-15.8) and 39.1 months (95% CI 32.5-48.6) in the MT cohort, respectively, and 8.6 months (95% CI 8.0-9.5) and 38.4 months (95% CI 36.4-41.0) in the AS cohort, respectively. Almost all patients had ≥ 1 RF (MT 95.3%; AS 96.7%). Median IPC-weighted TTNT was shorter among patients with more RF in both cohorts (MT: 1 RF, 19.3 months, 95% CI 13.5-37.8; 2 RF, 17.2 months, 95% CI 12.8-20.2; 3 RF, 11.0 months, 95% CI 8.2-13.8; 4 RF, 7.0 months, 95% CI 6.2-8.8; AS: 1 RF, 17.7 months, 95% CI 13.5-22.3; 2 RF, 10.2 months, 95% CI 9.1-11.5; 3 RF, 6.5 months, 95% CI 5.8-7.4; 4 RF, 4.1 months, 95% CI 3.5-4.5).ConclusionRegardless of RF number, MT was associated with longer TTNT in real-world patients with AOC.

Radio Frequency (RF) sputtered germanium (Ge) thin films were deposited on glass substrate at in situ annealing temperatures of 400, 450, 500, 550, and 600 °C. X‐ray diffraction (XRD) and Raman spectroscopy revealed that the Ge films were initially amorphous but transformed to polycrystalline after annealing at 450 °C. Further annealing up to 600 °C resulted in improved crystallinity. Strain studies of the films using XRD and Raman showed compressive (out‐of‐plane) and tensile (in‐plane) strains, respectively, throughout all the annealing temperatures. The surface morphology of the films was recorded using atomic force microscopy (AFM) and field emission scanning electron microscopy (FESEM), which showed grain growth with annealing temperatures. The optical energy gap evaluated from absorption spectra for crystalline films decreased with annealing temperature, indicating improvement in crystallinity of films. The resistivity of the films deduced using current‐voltage measurements was found to decrease with annealing temperature, which can be attributed to enhancement in grain size. This study establishes a correlation between strain, grain size, optical energy gap, and electrical resistivity with temperature for Ge films deposited on glass substrates. Thus, the present study provides insights into variation in physical and electrical properties of films with in situ annealing temperature for their applicability in optoelectronic devices. [ABSTRACT FROM AUTHOR]

Mouth cancer is the most frequent cancer of the head and neck in both older and younger people. Achyranthes aspera L. has been used in ethnotraditional and pharmacological applications since ancient times for a variety of disorders. This study was formulated to examine bioactive phenolic and flavonoid compounds from the ethanolic extract of Achyranthes aspera and their binding efficacy targeting growth factor receptors (GFRs) against mouth cancer through in silico molecular docking and simulation studies. Phytochemicals were investigated through the UHPLC technique. A molecular docking study was accomplished using docking software AutoDock 4.2, and MD simulation was executed through GROMACS software. Drug‐likeness, pharmacokinetics, and toxicity profiles of phytocompounds were evaluated using Molinspiration, Swiss ADME, OSIRIS Data Warrior tools, respectively. UHPLC analysis detected phenolics and flavonoids, viz., fisetin, rutin, and fumaric acid, which satisfied Lipinski's rule of five and pharmacokinetic properties. In molecular docking assessment, fisetin exhibited promising interactions with core targeted proteins VEGFR‐2 (B.E. = −8.30 kcal mol−1) and FGFR‐2 (B.E. = −7.64 kcal mol−1) of mouth cancer. Moreover, molecular dynamics simulation data demonstrated stable interactions with both VEGFR‐2 and FGFR‐2 proteins. This binding interaction and stability of A. aspera phytocompounds with therapeutic proteins might contribute to their therapeutic potential in mouth cancer management. [ABSTRACT FROM AUTHOR]