Future oncology
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Gene fusions involving NTRK1, NTRK2 and NTRK3 are oncogenic drivers across a wide variety of cancer types. Inhibitors of the chimeric TRKA/B/C protein kinases encoded by these fusions are now available, including larotrectinib, a potent and highly selective oral drug. ⋯ Larotrectinib has received accelerated approval from both the US FDA and the EMA. Resistance mutations have been observed in the kinase domains of the NTRK fusion genes and development of next-generation tropomyosin receptor kinase inhibitors designed to overcome such resistance mutations is being actively pursued in clinical trials and ongoing drug discovery efforts.
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The immune checkpoint inhibitors have opened new horizons in oncology. Although the indications for the use of Immune checkpoint inhibitors in cancer patients are expanding, there is still a need for markers that can aid in patient selection. Gastrointestinal microbiota can be among these markers. ⋯ Preclinical data suggest that modulation of the microbiota could become a novel strategy for improving the efficacy of immunotherapy. However, its labile structure prone to be affected by many factors. Further research can delineate the mechanisms of the relationship between microbiota and immunotherapy can have clinical implications.
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Aim: Prognostic factors in patients with distant metastatic pancreatic neuroendocrine tumors (PNETs) remain uncertain. The purpose of our study is to establish a nomogram to predict survival outcomes in patients with metastatic PNETs. Methods: A total of 878 patients diagnosed with PNETs in the Surveillance, Epidemiology and End Results database between 2004 and 2016 were retrospectively identified. ⋯ The original concordance index was 0.773 (95% CI: 0.751-0.795), and the bias-corrected concordance index was 0.769 (95% CI: 0.748-0.791). The internal calibration curves showed well consistency and veracity in predicting cancer-specific survival probabilities. Conclusion: A nomogram was constructed and verified to predict survival outcomes in patients with distant-stage PNETs.
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Randomized Controlled Trial Multicenter Study
Isatuximab plus carfilzomib/dexamethasone versus carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma: IKEMA Phase III study design.
Although the treatment of relapsed/refractory multiple myeloma has improved dramatically over the past decade, the disease remains incurable; therefore, additional therapies are needed. Novel combination therapies incorporating monoclonal antibodies have shown significant promise. Here we describe the design of a Phase III study (NCT03275285, IKEMA), which is evaluating isatuximab plus carfilzomib and low-dose dexamethasone, versus carfilzomib/dexamethasone in relapsed/refractory multiple myeloma. ⋯ Responses are being determined by an independent review committee using 2016 International Myeloma Working Group criteria, and safety will be assessed throughout. The first patient was recruited in November 2017, and the last patient was recruited in March 2019; 302 patients have been randomized, and the study is ongoing. Clinical trial registration: NCT03275285.
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Since the US FDA-approval of the first immune checkpoint inhibitor, anticytotoxic T-lymphocyte antigen-4 monoclonal antibody ipilimumab, for metastatic melanoma on 28 March 2011, another six agents have been granted use among a multitude of tumors, including renal cell cancer, Hodgkin lymphoma, urothelial carcinoma and non-small-cell lung cancer. The first anti-programmed cell death ligand-1 monoclonal antibody to receive the FDA approval, atezolizumab (Tecentriq®), has yielded promising results among international Phase III trials in triple-negative breast cancer and small-cell lung cancer, expanding the field of cancer immunotherapies. Herein, we review the pharmacodynamic and pharmacokinetic properties of atezolizumab, its safety and efficacy data from early clinical trials and summarize data from Phase III IMpassion130 trial, prompting FDA and EMA approval of atezolizumab in metastatic triple-negative breast cancer. Finally, implications for clinical use and ongoing research will be briefly discussed.