Phase II Study of Samotolisib in Children and Young Adults With Tumors Harboring Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Pathway Alterations: Pediatric MATCH APEC1621D.

Autor:	Laetsch TW; Children's Hospital of Philadelphia/University of Pennsylvania, Philadelphia, PA., Ludwig K; University of Texas Southwestern, Dallas, TX., Williams PM; Frederick National Laboratory for Cancer Research, Frederick, MD., Roy-Chowdhuri S; University of Texas MD Anderson Cancer Center, Houston, TX., Patton DR; Center for Biomedical Informatics and Information Technology, NCI, NIH, Bethesda, MD., Coffey B; Center for Biomedical Informatics and Information Technology, NCI, NIH, Bethesda, MD., Reid JM; Mayo Clinic Comprehensive Cancer Center, Rochester, MN., Piao J; Keck School of Medicine, University of Southern California, Los Angeles, CA., Saguilig L; Children's Oncology Group Statistical Center, Monrovia, CA., Alonzo TA; Keck School of Medicine, University of Southern California, Los Angeles, CA., Berg SL; Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX., Mhlanga J; Washington University School of Medicine, St Louis, MO., Fox E; St Jude Children's Research Hospital, Memphis, TN., Weigel BJ; University of Minnesota, Minneapolis, MN., Hawkins DS; Seattle Children's Hospital and University of Washington, Seattle, WA., Mooney MM; Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD., Takebe N; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD., Tricoli JV; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD., Janeway KA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA., Seibel NL; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD., Parsons DW; Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX.
Jazyk:	angličtina
Zdroj:	JCO precision oncology [JCO Precis Oncol] 2024 Sep; Vol. 8, pp. e2400258.
DOI:	10.1200/PO.24.00258
Abstrakt:	Purpose: Patients age 1-21 years with relapsed or refractory solid and CNS tumors were assigned to phase II studies of molecularly targeted therapies on the National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial. Patients whose tumors harbored predefined genetic alterations in the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway and lacked mitogen-activated protein kinase pathway activating alterations were treated with the PI3K/mTOR inhibitor samotolisib. Methods: Patients received samotolisib twice daily in 28-day cycles until disease progression or unacceptable toxicity. A rolling 6 limited dose escalation was performed as, to our knowledge, this was the first pediatric study of samotolisib. The primary end point was the objective response rate; secondary end points included progression-free survival (PFS) and the recommended phase II dose and toxicity of samotolisib in children. Results: A total of 3.4% (41/1,206) of centrally tested patients were matched to this arm. Seventeen patients were treated. Among treated patients, the most common diagnoses included osteosarcoma (n = 6) and high-grade glioma (n = 5) harboring alterations in phosphatase and tensin homolog (n = 6), PIK3CA (n = 5), and tuberous sclerosis complex 2 (n = 3). No objective responses or prolonged stable disease were observed. Three-month PFS was 12% (95% CI, 2 to 31). Two patients experienced dose-limiting toxicities (mucositis and pneumonitis). Dose level 2 (115 mg/m 2 /dose twice daily) was determined to be the recommended phase II dose of samotolisib in children. Conclusion: This nationwide study was successful at identifying patients and evaluating the efficacy of molecularly targeted therapy for rare molecular subgroups of patients in a histology-agnostic fashion. Unfortunately, there was no activity of samotolisib against tumors with PI3K/mTOR pathway alterations. Prospective trials such as the NCI-COG Pediatric MATCH are necessary to evaluate the efficacy of molecularly targeted therapies given their increasing use in clinical practice.
Databáze:	MEDLINE
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