Publications by authors named "David M O'Malley"
This randomized phase III trial aimed to determine whether treatment with cisplatin and volume-directed radiation followed by carboplatin and paclitaxel for four cycles (chemoradiotherapy [C-RT]) increased recurrence-free survival (RFS) and overall survival (OS) when compared with carboplatin and paclitaxel for six cycles (chemotherapy [CT]) in locally advanced endometrial cancer (UC). Previously reported results showed that C-RT did not improve RFS compared with CT. Here we report the final OS analysis.
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- The study analyzes the cost differences in managing hematologic adverse events (AEs) for the individualized starting dose (ISD) versus the fixed starting dose (FSD) of niraparib from a US payer perspective.
- Data from a phase III trial provided AE occurrence rates, and costs were calculated based on 2020 adjustments from a healthcare database.
- Results showed that managing AEs was significantly cheaper with ISD ($6744.93) compared to FSD ($12,987.71), suggesting ISD not only cuts costs but also improves patient safety.
Objectives: Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial.
Methods: Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years.
Article Synopsis
- Endometrial cancer (EC) is the most common gynecological cancer in the U.S., with obesity contributing to 57% of cases, emphasizing the need to study its molecular mechanisms in relation to obesity.
- The research found that obese EC patients had higher levels of extracellular vesicles (EVs) carrying oncogenic proteins, which are linked to increased cancer growth, inflammation, and changes in protein expression in both adipose and uterine tissues.
- Treatments with small molecule inhibitors like HO-3867 and Metformin were effective in reducing EV secretion, slowing cancer cell proliferation, and inhibiting the early stages of cancer development in high-fat diet-induced models.
GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301: a phase 3, randomized trial evaluating avutometinib plus defactinib compared with investigator's choice of treatment in patients with recurrent low grade serous ovarian cancer.
Int J Gynecol Cancer
October 2024
Article Synopsis
- There are no special treatments approved for low grade serous ovarian cancer, and the usual treatments don't always work well.
- A new combination of two medicines called avutometinib and defactinib might work better and is safer than regular treatments.
- The study wants to see if using this new combo helps patients live longer without their cancer getting worse compared to other treatments doctors might choose.
The use of glucagon-like peptide-1 receptor agonists (GLP-1RA) has experienced rapid growth amidst the obesity epidemic in the United States. While originally developed for glucose control in Type 2 Diabetes Mellitus, the scope of these agents now extends to encompass weight loss and cardiovascular risk reduction. GLP-1RAs have the potential to induce significant weight loss, in combination with lifestyle modifications, among adults who are overweight or obese.
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- Platinum-sensitive ovarian cancer (PSOC) is commonly treated with platinum-based chemotherapy plus bevacizumab, but patients often face disease progression within a year, indicating a need for new treatment strategies.
- Mirvetuximab soravtansine-gynx (MIRV), an antibody-drug conjugate targeting folate receptor alpha, has shown promising results when used with bevacizumab, particularly in patients with high levels of FRα.
- The ongoing Phase III GLORIOSA trial aims to compare the effectiveness of MIRV plus bevacizumab against bevacizumab alone for patients with FRα-high PSOC after responding to previous treatment.
Background: Ovarian cancer has the highest mortality among gynecologic cancers, primarily because it typically is diagnosed at a late stage and because of the development of chemoresistance in recurrent disease. Improving outcomes in women with platinum-resistant ovarian cancer is a substantial unmet need. Activation of the glucocorticoid receptor (GR) by cortisol has been shown to suppress the apoptotic pathways used by cytotoxic agents, limiting their efficacy.
View Article and Find Full Text PDFPatterns of initial ovarian cancer recurrence on niraparib maintenance monotherapy in patients with no baseline evidence of disease after first-line chemotherapy: An ad hoc subgroup analysis of PRIMA/ENGOT-OV26/GOG-3012.
Gynecol Oncol
October 2024
Article Synopsis
- The study analyzed how advanced ovarian cancer patients respond to niraparib maintenance therapy and patterns of disease recurrence.
- Of 314 patients, 190 developed new lesions, primarily in the peritoneum, lymph nodes, and liver, often seeing 1-3 new lesions upon progression.
- Findings suggest that while many patients develop oligometastatic disease at recurrence, further research is needed to assess if local therapies could enhance outcomes when combined with targeted maintenance therapy.
Purpose: Niraparib is a poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor approved for the maintenance treatment of advanced ovarian cancer (OC). Niraparib was originally approved in recurrent OC at a fixed starting dose (FSD) of 300 mg once daily (QD). This analysis characterized the population pharmacokinetics (PK) of niraparib and evaluated the relationships between exposure, efficacy, and safety to support clinical use of an individualized dosing strategy, in which the starting dose of niraparib was adjusted based on patient characteristics to improve the benefit-risk profile.
View Article and Find Full Text PDFObjective: To identify characteristics associated with long-term progression-free survival (≥2 years) in patients with advanced ovarian cancer treated with niraparib first-line maintenance therapy in the phase III PRIMA/ENGOT-OV26/GOG-3012 study.
Methods: In this post hoc analysis of PRIMA, patients randomized to niraparib were grouped based on investigator-assessed progression-free survival (progressive disease/censoring <2 years or ≥2 years after randomization). Variables assessed for predictive value were Eastern Cooperative Oncology Group performance status, International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis, clinical response to platinum-based chemotherapy, number of prior chemotherapy cycles, primary tumor location, body mass index, categorical age, debulking surgery type, number of baseline target lesions, number of baseline non-target lesions, /homologous recombination-deficiency status, residual disease status, and duration from end of chemotherapy to randomization.
A phase 2 trial exploring the significance of homologous recombination status in patients with platinum sensitive or platinum resistant relapsed ovarian cancer receiving combination cediranib and olaparib.
Gynecol Oncol
August 2024
Article Synopsis
- This study looked at how well a combination of two drugs, cediranib and olaparib, worked for treating ovarian cancer that came back after treatment.
- It involved 70 patients and compared those whose cancer was sensitive to a type of medicine called platinum with those whose cancer was resistant to it.
- The results showed that the drug combo helped patients with sensitive cancer a lot more than those with resistant cancer, but the presence of certain gene mutations didn’t seem to affect how well the drugs worked.
Advanced-stage endometrial and cervical cancers are associated with poor outcomes despite contemporary advances in surgical techniques and therapeutics. Recent clinical trial results have led to a shift in the treatment paradigm for both malignancies, in which immunotherapy is now incorporated as the standard of care up front for most patients with advanced endometrial and cervical cancers as the standard of care. Impressive response rates have been observed, but unfortunately, a subset of patients do not benefit from immunotherapy, and survival remains poor.
View Article and Find Full Text PDFPurpose: To assess efficacy and toxicity of cisplatin (C) and gemcitabine (G) with intensity-modulated radiation therapy (IMRT) in patients with locally advanced vulvar cancer not amenable to surgery.
Methods: Patients enrolled in a single-arm phase II study. Pretreatment inguinal-femoral nodal assessment was performed.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal).
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- The study aimed to assess the effectiveness and safety of a combination therapy using mirvetuximab soravtansine (MIRV), carboplatin, and bevacizumab for patients with recurrent, platinum-sensitive ovarian cancer.
- In a trial with 41 participants, results showed a high objective response rate of 83%, with a median duration of response of 10.9 months and progression-free survival of 13.5 months.
- Although adverse events were common, they were mostly mild to moderate, with thrombocytopenia being the main reason for dose adjustments, indicating the combination therapy was both active and tolerable.
Gastric-type endocervical adenocarcinoma (GEA), a rare subtype of cervical cancer, has garnered increasing attention recently for its distinctive histopathological features, unique classification, genetic characteristics, and variable clinical outcomes compared to squamous cell and adenocarcinoma subtypes. Historically, GEA has evolved from a poorly understood entity to a distinct subtype of cervical adenocarcinoma, only recently recognized in the 2020 World Health Organization (WHO) classification. Accordingly, characteristic morphological features define GEA, shedding light on the diagnostic challenges and potential misclassification that can occur in clinical practice.
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- The study looked at how well different combinations of drugs work for treating a type of ovarian cancer that comes back after treatment.
- Researchers compared patients who received a specific drug combination called carboplatin and pegylated liposomal doxorubicin with those who got other drug combinations before they started maintenance therapy with a drug called PARP inhibitor.
- The results showed that, although there were some differences in how long patients stayed cancer-free, the overall survival times were not significantly different, meaning more research is needed to understand which drug combination is better.
Purpose: Early results from the phase II MEDIOLA study (NCT02734004) in germline BRCA1- and/or BRCA2-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) showed promising efficacy and safety with olaparib plus durvalumab. We report efficacy and safety of olaparib plus durvalumab in an expansion cohort of women with gBRCAm PSROC (gBRCAm expansion doublet cohort) and two cohorts with non-gBRCAm PSROC, one of which also received bevacizumab (non-gBRCAm doublet and triplet cohorts).
Patients And Methods: In this open-label, multicenter study, PARP inhibitor-naïve patients received olaparib plus durvalumab treatment until disease progression; the non-gBRCAm triplet cohort also received bevacizumab.
Article Synopsis
- The definition of "platinum-resistant ovarian cancer" has changed, now also including cases where platinum treatment cannot be used; standard treatment involves single-agent non-platinum chemotherapy, with weekly paclitaxel showing better responses.* -
- Recent clinical trials have struggled to demonstrate significant improvements in outcomes for patients previously treated with bevacizumab, emphasizing the need for better treatment strategies, including combinations with antiangiogenics and immune checkpoint inhibitors.* -
- There is a critical need for improved clinical trial designs and biomarkers to enhance treatment responses in platinum-resistant cases, with ongoing research suggesting that understanding molecular phenotypes could lead to better-targeted therapies.*
Purpose: To evaluate the efficacy and safety of tucatinib and trastuzumab in patients with previously treated human epidermal growth factor receptor 2-positive (HER2+) metastatic biliary tract cancer (mBTC).
Methods: SGNTUC-019 (ClinicalTrials.gov identifier: NCT04579380) is an open-label phase II basket study evaluating the efficacy and safety of tucatinib and trastuzumab in patients with HER2-altered solid tumors.
Article Synopsis
- The study looked at how using antibiotics (ABX) and proton-pump inhibitors (PPI) affects the health of patients with endometrial cancer who got special chemotherapy.
- They found that using PPIs made patients live less time without cancer getting worse and also affected their overall survival negatively.
- The researchers believe they need to learn more about how these medicines interact with chemotherapy and the body's bacteria to help improve treatment for cancer patients.