Durvalumab and tremelimumab in patients with advanced rare cancer: a multi-centre, non-blinded, open-label phase II basket trial.

Background: Dual inhibition of cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) has been shown to be an effective treatment strategy in many cancers. We sought to determine the objective response rate of combination durvalumab (D) plus tremelimumab (TM) in parallel cohorts of patients with carefully selected rare cancer types in which these agents had not previously been evaluated in phase II trials and for which there was clinical or biological rationale for dual immune checkpoint inhibitor therapy to be active.

Methods: We designed a multi-centre, non-blinded, open-label phase II basket trial with each of the following 8 rare cancers considered a separate phase II trial: salivary carcinoma, carcinoma of unknown primary (CUP) with tumour infiltrating lymphocytes and/or expressing PD-L1, mucosal melanoma, acral melanoma, osteosarcoma, undifferentiated pleomorphic sarcoma, clear cell carcinoma of the ovary (CCCO) or squamous cell carcinoma of the anal canal (SCCA).

Marizomib for patients with newly diagnosed glioblastoma: A randomized phase 3 trial.

Background: Standard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT), and temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). The proteasome has long been considered a promising therapeutic target because of its role as a central biological hub in tumor cells. Marizomib is a novel pan-proteasome inhibitor that crosses the blood-brain barrier.

Evaluation of DNA Methylation Array for Glioma Tumor Profiling and Description of a Novel Epi-Signature to Distinguish IDH1/IDH2 Mutant and Wild-Type Tumors.

Unlabelled: Molecular biomarkers, such as mutations and 1p19q co-deletion, are included in the histopathological and clinical criteria currently used to diagnose and classify gliomas. mutation is a common feature of gliomas and is associated with a glioma-CpG island methylator phenotype (CIMP). Aberrant genomic methylation patterns can also be used to extrapolate information about copy number variation in a tumor.

Neoadjuvant and Adjuvant Systemic Therapy for Newly Diagnosed Stage II-IV Epithelial Ovary, Fallopian Tube, or Primary Peritoneal Carcinoma: A Practice Guideline.

Background: This study aims to provide guidance for the use of neoadjuvant and adjuvant systemic therapy in women with newly diagnosed stage II-IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma.

Methods: EMBASE, MEDLINE, and Cochrane Library were investigated for relevant systematic reviews and phase III trials. Articles focusing on consolidation and maintenance therapies were excluded.

Phase I study of daily and weekly regimens of the orally administered MDM2 antagonist idasanutlin in patients with advanced tumors.

Aim The oral MDM2 antagonist idasanutlin inhibits the p53-MDM2 interaction, enabling p53 activation, tumor growth inhibition, and increased survival in xenograft models. Methods We conducted a Phase I study of idasanutlin (microprecipitate bulk powder formulation) to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics, food effect, and clinical activity in patients with advanced malignancies. Schedules investigated were once weekly for 3 weeks (QW × 3), once daily for 3 days (QD × 3), or QD × 5 every 28 days.

Consolidation or maintenance systemic therapy for newly diagnosed stage II, III, or IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma: A systematic review.

Backgrounds: To systematically review the effectiveness and harm of consolidation or maintenance therapy in patients with newly diagnosed stage II-IV EOC.

Methods: MEDLINE, EMBASE, PubMed, Cochrane Library, and PROSPERO databases, and four relevant conferences were systematically searched. We adhered to PRISMA guidelines, and used the GRADE approach to aggregate data.

Neoadjuvant and adjuvant systemic therapy for newly diagnosed stage II- IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma: A systematic review.

Background: To systematically review neoadjuvant and adjuvant therapy options for women with newly diagnosed stage II-IV ovarian cancer.

Methods: Phase III trials were searched using MEDLINE, EMBASE, and Cochrane Library. Maintenance therapies were excluded.

Metabolic flexibility determines human NK cell functional fate in the tumor microenvironment.

NK cells are central to anti-tumor immunity and recently showed efficacy for treating hematologic malignancies. However, their dysfunction in the hostile tumor microenvironment remains a pivotal barrier for cancer immunotherapies against solid tumors. Using cancer patient samples and proteomics, we found that human NK cell dysfunction in the tumor microenvironment is due to suppression of glucose metabolism via lipid peroxidation-associated oxidative stress.

An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline: Consolidation or Maintenance Systemic Therapy for Newly Diagnosed Stage II, III, or IV Epithelial Ovary, Fallopian Tube, or Primary Peritoneal Carcinoma.

Objective: To provide recommendations on systemic therapy options in consolidation or maintenance therapy for women with newly diagnosed stage II, III, or IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma including all histological types.

Methods: Consistent with the Program in Evidence-based Program's standardized approach, MEDLINE, EMBASE, PubMed, Cochrane Library, and PROSPERO (the international prospective register of systematic reviews) databases, and four relevant conferences were systematically searched. The Working Group drafted recommendations and revised them based on the comments from internal and external reviewers.

The Effect of Renal Impairment on the Pharmacokinetics and Safety of Talazoparib in Patients with Advanced Solid Tumors.

Background: Pharmacokinetic (PK) studies suggest that talazoparib is primarily eliminated unchanged via renal excretion. The current study investigated how varying degrees of renal impairment may affect the PK of talazoparib, and evaluated the safety and tolerability of talazoparib, in patients with advanced solid tumors with/without renal impairment.

Methods: Patients with advanced solid tumors and normal renal function or different degrees of renal impairment measured by estimated glomerular filtration rate (eGFR: mild = 60-89, moderate = 30-59, severe = 15-29 mL/min/1.

Cediranib in addition to chemotherapy for women with relapsed platinum-sensitive ovarian cancer (ICON6): overall survival results of a phase III randomised trial.

Background: Cediranib, an oral anti-angiogenic VEGFR 1-3 inhibitor, was studied at a daily dose of 20 mg in combination with platinum-based chemotherapy and as maintenance in a randomised trial in patients with first relapse of 'platinum-sensitive' ovarian cancer and has been shown to improve progression-free survival (PFS).

Patients And Methods: ICON6 (NCT00532194) was an international three-arm, double-blind, placebo-controlled randomised trial. Between December 2007 and December 2011, 456 women were randomised, using stratification, to receive either chemotherapy with placebo throughout (arm A, reference); chemotherapy with concurrent cediranib, followed by maintenance placebo (arm B, concurrent); or chemotherapy with concurrent cediranib, followed by maintenance cediranib (arm C, maintenance).

A pneumococcal pneumonia and influenza vaccination quality improvement program for women receiving chemotherapy for gynecologic cancers at a major tertiary cancer Centre.

Objective: International guidelines recommend pneumococcal pneumonia and influenza vaccination for all patients with solid organ malignancies prior to initiating chemotherapy. Baseline vaccination rates (March 2019) for pneumococcal pneumonia and influenza at our tertiary cancer centre were 8% and 40%, respectively. The aim of this study was to increase the number of gynecologic chemotherapy patients receiving pneumococcal and influenza vaccinations to 80% by March 2020.

Characterization of Mutational Status, Spheroid Formation, and Drug Response of a New Genomically-Stable Human Ovarian Clear Cell Carcinoma Cell Line, 105C.

Ovarian clear cell carcinoma (OCCC) is a rare subtype of gynecological cancer for which well-characterized and authenticated model systems are scarce. We provide an extensive characterization of '105C', a cell line generated from an adenocarcinoma of the clear cell histotype using targeted next-generation sequencing, cytogenetic microarrays, along with analyses of AKT/mTOR signaling. We report that that the 105C cell line is a bona fide OCCC cell line, carrying PIK3CA, PTEN, and ARID1A gene mutations, consistent with OCCC, yet maintain a stable genome as reflected by low copy number variation.

Bullous vesicant-type reaction to docetaxel along the venous tract: A case report.

Docetaxel is an anti-neoplastic agent commonly used to treat major solid tumors. Common toxicities of docetaxel include neutropenia, alopecia, nausea and vomiting. While docetaxel is typically considered an irritant, we present the case report of a 54-year-old female with high-grade undifferentiated uterine sarcoma who experienced a standard infusion reaction during a docetaxel infusion, followed by an atypical, delayed vesicant-type reaction, without a clear extravasation history.

Impact of COVID-19 on Canadian medical oncologists and cancer care: Canadian Association of Medical Oncologists survey report.

Background: The covid-19 pandemic has presented unprecedented professional and personal challenges for the oncology community. Under the auspices of the Canadian Association of Medical Oncologists, we conducted an online national survey to better understand the impact of the pandemic on the medical oncology community in Canada.

Methods: An English-language multiple-choice survey, including questions about demographics, covid-19 risk, use of personal protective equipment (ppe), personal challenges, and chemotherapy management was distributed to Canadian medical oncologists.

Phase II Trial of Cabozantinib in Recurrent/Metastatic Endometrial Cancer: A Study of the Princess Margaret, Chicago, and California Consortia (NCI9322/PHL86).

Purpose: The relevance of the MET/hepatocyte growth factor pathway in endometrial cancer tumor biology supports the clinical evaluation of cabozantinib in this disease.

Patients And Methods: PHL86/NCI#9322 (NCT01935934) is a single arm study that evaluated cabozantinib (60 mg once daily) in women with endometrial cancer with progression after chemotherapy. Coprimary endpoints were response rate and 12-week progression-free-survival (PFS).

A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.

Purpose: Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer.

Dose-Ranging and Cohort-Expansion Study of Monalizumab (IPH2201) in Patients with Advanced Gynecologic Malignancies: A Trial of the Canadian Cancer Trials Group (CCTG): IND221.

Purpose: Monalizumab binds CD94/NKG2A, preventing HLA-E inhibition of tumor lymphocytes. A dose-ranging/cohort expansion trial of monalizumab for recurrent gynecologic malignancies was conducted to determine the recommended phase II dose (RP2D) and to explore clinical activity, pharmacokinetics, pharmacodynamics, safety, and immunogenicity.

Patients And Methods: Participants (and part 2 expansion cohorts) included (i) platinum-sensitive ovarian, (ii) platinum-resistant ovarian, (iii) squamous cervical (CX), and (iv) epithelial endometrial (END) carcinomas.

Phase I Study of BI 853520, an Inhibitor of Focal Adhesion Kinase, in Patients with Advanced or Metastatic Nonhematologic Malignancies.

Background: Overexpression/activation of focal adhesion kinase (FAK) in human malignancies has led to its evaluation as a therapeutic target. We report the first-in-human phase I study of BI 853520, a novel, potent, highly selective FAK inhibitor.

Objective: Our objectives were to identify the maximum tolerated dose (MTD), and to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), biomarker expression, and preliminary activity.

Randomized, Open-Label, Crossover Studies Evaluating the Effect of Food and Liquid Formulation on the Pharmacokinetics of the Novel Focal Adhesion Kinase (FAK) Inhibitor BI 853520.

Background: BI 853520 is a potent inhibitor of focal adhesion kinase and is currently under clinical development for the treatment of non-hematological malignancies.

Objective: The objective of this study was to evaluate the effect of food and liquid dispersion on the pharmacokinetics of BI 853520 in two open-label, crossover substudies.

Patients And Methods: Sixteen patients with advanced solid tumors were enrolled in each substudy.

Evolution of genetic assessment for BRCA-associated gynaecologic malignancies: a Canadian multisociety roadmap.

The landscape of genetic testing in ovarian cancer patients has changed dramatically in recent years. The therapeutic benefits of poly ADP-ribose polymerase (PARP) inhibitors in treatment of -related ovarian cancers has resulted in an increased demand and urgency for genetic testing results, while technological developments have led to widespread use of multi-gene cancer panels and development of tumour testing protocols. Traditional genetic counselling models are no longer sustainable and must evolve to match the rapid evolution of genetic testing technologies and developments in personalized medicine.

Expanded CD56CD16 NK Cells from Ovarian Cancer Patients Are Cytotoxic against Autologous Tumor in a Patient-Derived Xenograft Murine Model.

Natural killer (NK) cells are useful for cancer immunotherapy and have proven clinically effective against hematologic malignancies. However, immunotherapies for poor prognosis solid malignancies, including ovarian cancer, have not been as successful due to immunosuppression by solid tumors. Although rearming patients' own NK cells to treat cancer is an attractive option, success of that strategy is limited by the impaired function of NK cells from cancer patients and by inhibition by self-MHC.