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Futibatinib for advanced intrahepatic cholangiocarcinoma with an FGFR2 gene fusion or rearrangement (October 2022)
Futibatinib, a highly selective inhibitor of fibroblast growth factor receptor (FGFR) 1 to 4, has been approved by the US Food and Drug Administration for treatment of locally advanced/metastatic intrahepatic cholangiocarcinoma with an FGFR2 gene fusion or rearrangement [1]. Approval was based on the phase II FOENIX-CCA2 study, which showed an objective response rate of 42 percent, a mean duration of response of 9.5 months, and no new safety signals [2]. The most common treatment-related adverse effects were hyperphosphatemia, alopecia, dry mouth, diarrhea, dry skin, and fatigue.
Doxorubicin and trabectedin as first-line therapy for advanced leiomyosarcoma (October 2022)
The combination of doxorubicin plus trabectedin holds promise in metastatic leiomyosarcoma (LMS). In a randomized trial including 150 patients with metastatic leiomyosarcoma of uterine or nonuterine soft tissue sarcoma origin, progression-free survival was longer in patients assigned to doxorubicin plus trabectedin followed by trabectedin versus doxorubicin alone (12.2 versus 6.2 months, adjusted hazard ratio 0.41) [3]. Improvements were noted in both the nonuterine and uterine subgroups. The most common grade >=3 adverse events with and without trabectedin were neutropenia (80 versus 13 percent), anemia (31 versus 5 percent), thrombocytopenia (47 versus 0 percent), and febrile neutropenia (28 versus 9 percent). We consider doxorubicin plus trabectedin followed by trabectedin to be an acceptable option for the initial treatment of fit patients with advanced LMS.
Proton craniospinal irradiation in patients with solid tumor leptomeningeal disease (October 2022)
For patients with leptomeningeal disease (LMD) from solid tumors, craniospinal irradiation (CSI) with photons is typically not appropriate due to high risk of toxicity and low likelihood of meaningful benefit. However, proton CSI has an improved toxicity profile compared with photon CSI, and there has been renewed interest in its role. In a randomized phase II trial of proton CSI versus involved field radiation in 63 patients with LMD from either breast cancer or non-small cell lung cancer, proton CSI improved both median central nervous system progression-free survival (7.5 versus 2.3 months) and overall survival (9.9 versus 7.5 months) compared with involved field radiation, with no difference in the rate of serious adverse effects [4]. Although more data are needed, where available, proton CSI is an option in selected patients with LMD who have adequate functional status and controlled systemic disease.
Pimitespib for advanced gastrointestinal stromal tumors (October 2022)
For patients with advanced gastrointestinal stromal tumors (GIST) who have progressed on multiple tyrosine kinase inhibitors, there is interest in novel targeted agents. In a phase III trial in almost 90 patients with advanced GIST refractory to imatinib, sunitinib, and regorafenib, the heat-shock protein 90 inhibitor pimitespib improved median progression-free survival (2.8 versus 1.4 months) compared with placebo, as well as cross-over-adjusted median overall survival (14 versus 8 months) [5]. For patients with advanced GIST refractory to imatinib, sunitinib, and regorafenib, pimitespib is an acceptable treatment option, but is available only in Japan.
Guideline on circumscribed astrocytic gliomas, glioneuronal, and neuronal tumors (October 2022)
A new multinational guideline is available on the diagnosis and treatment of rare glial and neuronal tumors in children and adults [6]. Over 20 tumors are included in the guideline, corresponding to the 2021 update of the World Health Organization classification of central nervous system tumors. Surgery is the cornerstone of management for nearly all of these tumors, and radiation therapy is used selectively in the adjuvant and recurrent/refractory setting. Relevant molecular markers and targeted therapies are also reviewed.
1. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accele (Accessed on October 03, 2022).
2. Goyal L, et al. Updated results of the FOENIX-CCA2 trial: Efficacy and safety of futibatinib in intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/rearrangements (abstract). J Clin Oncol 40, 2022 (suppl 16; abstr 4009).
3. Pautier P, Italiano A, Piperno-Neumann S, et al. Doxorubicin alone versus doxorubicin with trabectedin followed by trabectedin alone as first-line therapy for metastatic or unresectable leiomyosarcoma (LMS-04): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol. 2022;23(8):1044. Epub 2022 Jul 11.
4. Yang JT, Wijetunga NA, Pentsova E, et al. Randomized Phase II Trial of Proton Craniospinal Irradiation Versus Photon Involved-Field Radiotherapy for Patients With Solid Tumor Leptomeningeal Metastasis. J Clin Oncol. 2022.
5. Kurokawa Y, Honma Y, Sawaki A, et al. Pimitespib in patients with advanced gastrointestinal stromal tumor (CHAPTER-GIST-301): a randomized, double-blind, placebo-controlled phase III trial. Ann Oncol. 2022;33(9):959. Epub 2022 Jun 8.
6. Ruda R, Capper D, Waldman AD, et al. EANO - EURACAN - SNO Guidelines on circumscribed astrocytic gliomas, glioneuronal, and neuronal tumors. Neuro Oncol. 2022.
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