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      Combination of Osimertinib with Concurrent Chemotherapy and Hormonal Therapy for Synchronous NSCLC, Hormone Receptor-Positive Breast Cancer, and Triple-Negative Breast Cancer: Case Report

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          Abstract

          Patients presenting with multiple primary malignancies remain a growing challenge for physicians due to a lack of data for generalizable guidelines. Identification of driver mutations in carcinogenesis leads to the development of targeted treatment of many different cancer types, but its combination with other anti-cancer therapy is not well understood. We report a case of a 66-year-old woman who presented with triple-negative breast cancer, multifocal hormone receptor-positive breast cancer, primary epidermal growth factor receptor-mutated lung adenocarcinoma, possible primary lung adenocarcinoma of unspecified mutational status in the contralateral lung, and a solitary metastatic lesion in the brain from one of her primary cancers. She was treated with stereotactic radiosurgery and osimertinib in combination with carboplatin/nab-paclitaxel, doxorubicin/cyclophosphamide, and letrozole, with excellent clinical and radiographical response. We did not observe synergistic toxicity or unexpected adverse events from the treatment. To the best of our knowledge, this is the first report of concurrent osimertinib with these chemotherapy and hormonal therapy agents. As large-scale studies are difficult to conduct for these rare cases requiring exceptional treatment, it is important for physicians to build on the community’s shared experience via case reports to better predict efficacy and safety of combining targeted agents with other conventional systemic treatments.

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          Most cited references18

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          Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC

          Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46). Data from the final analysis of overall survival have not been reported.
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            Multiple primary tumours: challenges and approaches, a review

            When in a patient more than one tumour in the same or a different organ is diagnosed, multiple primary tumours may be present. For epidemiological studies, different definitions of multiple primaries are used with the two main definitions coming from the project Surveillance Epidemiology and End Results and the International Association of Cancer Registries and International Agency for Research on Cancer. The differences in the two definitions have to be taken into consideration when reports on multiple primaries are analysed. In this review, the literature on multiple primaries is reviewed and summarised. Overall, the frequency of multiple primaries is reported in the range of 2–17%. Aetiological factors that may predispose patients to multiple primaries can be grouped into host related, lifestyle factors and environmental influences. Some of the most common cancer predisposition syndromes based on a clinical presentation are discussed and the relevant genetic evaluation and testing are characterised. Importantly, from a clinical standpoint, clinical situations when multiple primaries should be suspected and ruled out in a patient are discussed. Furthermore, general principles and possible treatment strategies for patients with synchronous and metachronous multiple primary tumours are highlighted.
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              TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer

              Osimertinib is a potent, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The multi-arm phase Ib TATTON study (NCT02143466) was designed to assess the safety and tolerability of osimertinib in combination with other targeted therapies: selumetinib (MEK1/2 inhibitor), savolitinib (MET-TKI), or durvalumab [anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibody].
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                Author and article information

                Journal
                Case Rep Oncol
                Case Rep Oncol
                CRO
                CRO
                Case Reports in Oncology
                S. Karger AG (Basel, Switzerland )
                1662-6575
                11 October 2023
                Jan-Dec 2023
                11 October 2023
                : 16
                : 1
                : 1080-1086
                Affiliations
                [1]Department of Medical Oncology, McGill University Health Center, McGill University, Montreal, QC, Canada
                Author notes
                Correspondence to: Ramy R. Saleh, Ramy.saleh@ 123456mail.mcgill.ca
                Article
                533783
                10.1159/000533783
                10601812
                37900833
                41dcf9b0-184b-4bbb-a25b-a9b4204d2de6
                © 2023 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ( http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 10 August 2023
                : 22 August 2023
                : 2023
                Page count
                Figures: 2, References: 18, Pages: 7
                Funding
                There were no sources of funding for this study.
                Categories
                Case Report

                Oncology & Radiotherapy
                multiple primary malignancy,osimertinib,chemotherapy,epidermal growth factor receptor,non-small cell lung cancer,breast cancer

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