1. Palbociclib in Patients With Soft Tissue Sarcoma With CDK4 Amplifications: Results From the Targeted Agent and Profiling Utilization Registry Study.
- Author
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Schuetze S, Rothe M, Mangat PK, Garrett-Mayer E, Meric-Bernstam F, Calfa CJ, Farrington LC, Livingston MB, Wentzel K, Behl D, Kier Y, Marr AS, von Mehren M, Press JZ, Thota R, Grantham GN, Gregory A, Hinshaw DC, Halabi S, and Schilsky RL
- Subjects
- Humans, Female, Male, Middle Aged, Adult, Aged, Gene Amplification, Young Adult, Aged, 80 and over, Cyclin-Dependent Kinase 4 genetics, Cyclin-Dependent Kinase 4 antagonists & inhibitors, Pyridines therapeutic use, Piperazines therapeutic use, Sarcoma drug therapy, Sarcoma genetics, Registries
- Abstract
Purpose: Targeted Agent and Profiling Utilization Registry (TAPUR) is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with soft tissue sarcoma with cyclin-dependent kinase 4 ( CDK4 ) amplification treated with palbociclib are reported., Methods: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0 to 2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration (SD16+) according to RECIST v1.1. The DC rate was estimated with a 90% CI. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety., Results: Forty-two patients with CDK4 amplification were enrolled. One patient was not evaluable for efficacy. One patient with partial response and 18 with SD16+ were observed for DC and OR rates of 46% (90% CI, 36 to 100) and 2% (95% CI, <1 to 13), respectively. Median PFS was 16 weeks (95% CI, 9 to 28) and median OS was 69 weeks (95% CI, 31 to 111) for evaluable patients. Twenty patients had at least one grade 3 to 4 adverse event (AE) at least possibly related to palbociclib, including alanine aminotransferase increase, anemia, fatigue, hypophosphatemia, leukopenia, neutropenia, and thrombocytopenia. No serious AEs were reported., Conclusion: Palbociclib met prespecified criteria to declare a signal of antitumor activity in patients with sarcoma and CDK4 amplification.
- Published
- 2024
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