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Margetuximab in metastatic HER2-positive breast cancer
Margetuximab is an Fc-engineered anti-HER2 receptor monoclonal antibody that has recently been approved by the US Food and Drug Administration, in combination with chemotherapy, for treatment of metastatic HER2-positive breast cancer in patients who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease [1]. In the phase III SOPHIA trial, among over 530 patients with disease progression after at least two lines of anti-HER2 therapy, the addition of margetuximab to chemotherapy prolonged median progression-free survival relative to trastuzumab plus chemotherapy (5.8 versus 4.9 months) with similar rates of overall survival [2]. Serious adverse events were comparable between the two groups. We consider this an appropriate later-line option in patients with metastatic HER2-positive breast cancer.
Hereditary diffuse gastric cancer risk in CDH1 carriers with no family history of gastric cancer
Prophylactic total gastrectomy is recommended for asymptomatic carriers of a pathogenic variant in the E-cadherin gene (CDH1) who have a family history of diffuse gastric cancer (DGC), while management of carriers with no family history of DGC is uncertain. In a study of pathogenic CDH1 variant carriers, six carriers with no family history of DGC (some had invasive lobular breast cancer) underwent prophylactic total gastrectomy and four had occult early signet ring cancer on final pathology [3]. These findings suggest at least a moderate risk of DGC in pathogenic CDH1 variant carriers with no family history of DGC. Once identified (most often by multigene panels for unrelated cancers), we suggest evaluating such patients at a center specializing in screening for and treatment of hereditary DGC.
First oral GnRH agonist approved for treatment of advanced prostate cancer
Relugolix, an oral gonadotropin releasing hormone (GnRH) antagonist, has been approved by the US Food and Drug Administration for the treatment of adult men with advanced prostate cancer [4]. The superiority of relugolix over the GnRH agonist leuprolide was shown in the phase III HERO study, in which relugolix achieved more rapid and prolonged suppression of testosterone levels and had fewer major cardiovascular events, especially in men with a history of cardiovascular events [5]. We consider relugolix to be an appropriate alternative to a GnRH agonist or dagarelix (a parenterally administered GnRH antagonist), but not yet preferred for initial androgen deprivation therapy treatment of advanced prostate cancer, pending evaluation of cost, compliance, availability, and insurance coverage.
Six versus twelve cycles of post-radiation temozolomide in glioblastoma
In patients with newly diagnosed glioblastoma who complete six cycles of post-radiation temozolomide and have stable disease, there has been some uncertainty as to whether additional cycles of temozolomide might improve outcomes. In a phase II randomized trial of 159 such patients, those randomly assigned to continue temozolomide for up to 12 total cycles had similar progression-free and overall survival compared with those who were assigned to stop temozolomide after six cycles [6]. The incidence of lymphopenia, thrombocytopenia, and nausea was higher in the extended chemotherapy group. These results are consistent with most previous observational studies, which also failed to show a net benefit of more than six cycles of post-radiation temozolomide in patients with glioblastoma.
Revised REMS for transmucosal immediate release fentanyl preparations
For patients with chronic cancer-related pain who are receiving long-acting opioids, breakthrough pain may be targeted with one of the newer rapid-onset, transmucosal immediate release fentanyl (TIRF) formulations, which are specifically indicated for opioid-tolerant cancer patients. In the United States, all of these products, including generics, have a mandatory shared risk evaluation and mitigation strategy, the purpose of which is to reduce the risk of misuse and unintentional overdose. Because of data suggesting that TIRF preparations are still being prescribed to opioid-naive patients, additional regulations have been put into place by the US Food and Drug Administration, requiring that opioid tolerance be verified and documented by both the prescriber and the outpatient pharmacy, prior to each individual TIRF prescription [7].
1. Margetuximab-cmkb injection. United States Prescribing Information. US National Library of Medicine. https://www.margenza.com/pdf/prescribing-information.pdf (Accessed on December 18, 2020).
2. Rugo HS, Im SA, Cardoso F, et al. SOPHIA Study Group. Phase 3 SOPHIA study of margetuximab + chemotherapy versus trastuzumab + chemotherapy in patients with HER2+ metastatic breast cancer after prior anti-HER2 therapies: Second interim overall survival analysis. Cancer Res 2020; 80S: SABCS #GS1-02.
3. Vos EL, Salo-Mullen EE, Tang LH, et al. Indications for Total Gastrectomy in CDH1 Mutation Carriers and Outcomes of Risk-Reducing Minimally Invasive and Open Gastrectomies. JAMA Surg 2020; 155:1050.
4. FDA Approves First Oral Hormone Therapy for Treating Advanced Prostate Cancer. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-horm (Accessed on December 21, 2020).
5. Shore ND, Saad F, Cookson MS, et al. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med 2020; 382:2187.
6. Balana C, Vaz MA, Manuel Sepulveda J, et al. A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond 6 cycles in patients with glioblastoma (GEINO 14-01). Neuro Oncol 2020; 22:1851.
7. FDA Takes Further Steps to Confront Opioid Crisis Through Risk Evaluation and Mitigation Strategy Programs. Available at: https://www.fda.gov/news-events/press-announcements/fda-takes-further-steps-conf (Accessed on January 04, 2021).
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