Browsing by Author "Dawood, Shaheenah"

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Entrectinib for NTRK Fusion-Positive Metastatic Melanoma Progressing on Combined PD-1 and CTLA-4 Inhibition: A Case Report
(2023) Dawood, Shaheenah
Introduction: The burden of melanoma is increasing globally. Despite the use of immunotherapy and targeted therapy, the prognosis of metastatic melanoma remains relatively poor. The integration of comprehensive molecular profiling can lead to the detection of actionable biomarkers and the expansion of treatment options, thereby prolonging cancer patient survival. Case Presentation: We herein present the case of a female 54-year-old patient diagnosed with melanoma of the right knee, for which she underwent surgery. Patient showed progression of disease after 10 cycles of adjuvant nivolumab. Ipilimumab (1 mg/kg every 3 weeks) was added to the treatment regimen but no clinical improvement was observed. Molecular profiling was conducted based on patient tissue, and an ANXA2-NTRK3 fusion was detected in the tumor. This specific fusion has not been previously reported; however, it is in-frame and similar to other known oncogenic NTRK fusions. At the time of entrectinib initiation, the patient had clear disease progression on the right leg on standard of care immunotherapy. She was commenced on entrectinib 200 mg once daily for 2 weeks. Dose escalation was attempted, and treatment intensity was managed based on drug tolerability. Good treatment response was observed on laboratory and radiologic parameters. As of September 2023, i.e., 2.5 years after treatment initiation, patient disease continues to be controlled with entrectinib. Conclusion: Profiling of advanced tumors is important to determine the presence of agnostic markers that can be targeted and ultimately improve the prognostic outcome of patients after the failure of standard of care.
Impact of the Latest Clinical Data among Patients with Breast Cancer in Low- and Middle-Income Countries
(2022-12) Dawood, Shaheenah
Introduction: In June 2022, experts from the oncology world gathered in Chicago, Illinois, for the American Society of Clinical Oncology (ASCO) 2022 annual meeting. In this article, we review the latest advancements presented at the conference regarding metastatic breast cancer [1]. Then, with experts in the field, we discuss the scientific findings from the studies presented and the practical implications of these data among breast cancer patients in low- and middle-income countries.
Indirect Treatment Comparison of First-Line CDK4/6-Inhibitors in Post-Menopausal Patients with HR+/HER2− Metastatic Breast Cancer
(2023) Dawood, Shaheenah
Background: CDK4/6-inhibitors have demonstrated similar efficacy and are considered an effective first-line endocrine treatment of patients with hormone-receptor positive (HR+)/humanepidermal-growth-factor-receptor-2 negative (HER2−) metastatic breast cancer (MBC) in the endpoint of progression-free survival (PFS). Amongst these, palbociclib was first to achieve regulatory approval, followed subsequently by ribociclib and abemaciclib. However, recent updates of overall survival (OS) showed inconsistencies in the OS benefit for palbociclib compared with the other two CDK4/6-inhibitors. With the lack of head-to-head comparison studies, our study sought to compare indirect survival outcomes between CDK4/6-inhibitors in this setting using a novel reconstructive algorithm. Methods: Phase III randomized trials comparing first-line aromatase inhibitor with/without a CDK4/6-inhibitor in post-menopausal patients with HR+/HER2− MBC were identified through systemic review and literature search of online archives of published manuscripts and conference proceedings. A graphical reconstructive algorithm was utilized to retrieve time-to-event data from reported Kaplan-Meier OS and PFS plots to allow for comparison of survival outcomes. Survival analyses were conducted with Cox proportional-hazards model with a shared-frailty term. Results: Three randomized phase III trials—PALOMA-2, MONALEESA-2 and MONARCH-3— comprising 1827 patients were included. Indirect pairwise comparisons of all CDK4/6-inhibitors showed no significant PFS differences (all p > 0.05). Likewise, indirect treatment comparison between ribociclib vs. palbociclib (one-stage: HR = 0.903, 95%-CI: 0.746–1.094, p = 0.297), abemaciclib vs. palbociclib (one-stage: HR = 0.843, 95%-CI: 0.690–1.030, p = 0.094) and abemaciclib vs. ribociclib (onestage: HR = 0.933, 95%-CI: 0.753–1.157, p = 0.528) failed to demonstrate a significant OS difference. Conclusions: Findings from this indirect treatment comparison suggest no significant PFS or OS differences between CDK4/6-inhibitors in post-menopausal patients with HR+/HER2− MBC.
Negative Effects On Cancer Care Due To COVID-19 Implications: Observations From A Cancer Center In The UAE
(2020) Dawood, Shaheenah; Al-Hamadi, Annett
Abstract: In 2019, the World Health Organization declared the novel coronavirus disease (COVID-19) to be a public health emergency of international concern that rapidly escalated to pandemic status in 2020 (1). As of August 2, 2020, there have been approximately 17.6 million confirmed cases worldwide, with over 680,000 deaths from this disease (1). A particularly vulnerable cohort due to immunosuppression are those that suffer from cancer. On the 14th of February 2020 a nationwide analysis was published of patients suffering from COVID-19 in China that indicated that 18 of 1590 patients (1%) had a history of cancer and had higher risk of respiratory complications, more time spent in the intensive care unit, and a shorter time to deterioration compared to patients who did not have cancer (2). On the 28th of May 2020 we saw the results of the COVID-19 and Cancer Consortium (CCC19) database that reported a 30 day all-cause mortality of 13 % among patients with either active or previous history of cancer who had contracted COVID-19 with higher rates observed among those who were older, had poor performance status or were receiving active cancer related therapy (3). Various groups have made recommendations that include modifications in adjuvant therapy, delay in surgery and chemotherapy if feasible, and de-prioritizing patients with metastatic cancer and delayed screening s rategies (4). Although these recommendations were sensible in light of the pandemic, the clinical care pathway for patients with cancer that have been built. over the years in an effort to ensure early detection and therapy have been severely disrupted. As we pass the peak of the pandemic, the negative impact of our decisions will now become more visible.
Optimizing the management of HER2-negative metastatic breast cancer in the era of PARP inhibitors—proceedings from breast cancer expert group meeting
(2020) Dawood, Shaheenah
Abstract: The therapeutic landscape of human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (mBC) has evolved considerably with the introduction of newer targeted agents such as poly-ADP ribose polymerase inhibitors (PARPi), novel chemotherapeutic agents, immunotherapy, and endocrine therapies. In this scenario, optimizing the appropriate treatment sequence is a daunting task for clinicians. To develop evidence-based answers to key clinical questions on treatment selection and appropriate treatment sequence for the management of patients with HER2− mBC in the era of PARPi, a breast cancer expert group meeting was convened. The expert panel comprised of eight key opinion leaders from Argentina, Brazil, Colombia, Egypt, Mexico, Moscow, South Korea, and the United Arab Emirates, who convened and reviewed the literature, discussed the clinical practices across the participating regions, and formulated answers to key clinical questions for optimizing the management of HER2− mBC. In this review, evidence-based answers have been provided pertaining to (I) the specific mBC population to be considered for BRCA testing, optimal time point of BRCA testing, and genetic counselling in mBC patients; (II) the role of PARPi versus platinum therapy in HER2− mBC patients in the metastatic setting; (III) sequencing treatment in metastatic triple-negative breast cancer (TNBC) and hormone receptor-positive HER2− mBC patients, and defining the place of PARPi in the sequencing algorithms; and (IV) the need for a breast cancer registry for patients with HER2− mBC. This expert review will serve as a comprehensive guide to clinicians for optimizing BRCA testing and managing patients with BRCA mutation (BRCAm) and HER2− mBC. The data collected from the proposed HER2− mBC registry will help understand the treatment practices, identify unmet needs, and develop strategic policies regionally to help improve access to optimized care of HER2− mBC.
Reporting quality of practice guidelines on colorectal cancer: evaluation using the RIGHT reporting checklist
(2021) Dawood, Shaheenah
Background: Clinical practice guidelines are an essential tool for translating evidence into practice. Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist assists to guide the reporting in guidelines. We used RIGHT to assess the reporting completeness and quality of guidelines on colorectal cancer (CRC). Methods: We searched the electronic databases Medline (via PubMed), Chinese National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature (CBM) from January 1st, 2018 to December 1st, 2020 for guidelines on CRC. Websites of guideline development organizations were also searched. Two investigators assessed the reporting quality of the included guidelines, and calculated the numbers of guidelines that were compliant with each RIGHT checklist item and the mean proportions of reported items for each of the seven RIGHT checklist domains. Results: Twenty-seven colorectal guidelines were included. The proportions of reported items in each RIGHT domain were 71.0% for Basic information, 66.2% for Background, 45.9% for Evidence, 68.8% for Recommendations, 24.1% for Review and quality assurance, 33.3% for Funding and declaration and management of interests, and 40.7% for Other information. Conclusions: The reporting quality of colorectal guidelines was moderate. A systematic use of the RIGHT checklist during the development process could improve the reporting quality of guidelines in the future.