Phase II study of palbociclib in patients with tumors with CDK4 or CDK6 amplification: Results from the NCI-MATCH ECOG-ACRIN trial (EAY131) subprotocol Z1C Journal Article
| Authors: | O’Hara, M. H.; Jegede, O.; Dickson, M. A.; DeMichele, A. M.; Piekarz, R.; Gray, R. J.; Wang, V.; McShane, L. M.; Rubinstein, L. V.; Patton, D. R.; Williams, P. M.; Hamilton, S. R.; Onitilo, A.; Tricoli, J. V.; Conley, B. A.; Arteaga, C. L.; Harris, L. N.; O’Dwyer, P. J.; Chen, A. P.; Flaherty, K. T. |
| Article Title: | Phase II study of palbociclib in patients with tumors with CDK4 or CDK6 amplification: Results from the NCI-MATCH ECOG-ACRIN trial (EAY131) subprotocol Z1C |
| Abstract: | Purpose: Amplification of cyclin-dependent kinase 4 (CDK4) and CDK6 is a feature of a variety of malignancies, and preclinical evidence suggests that inhibition of CDK4/6 is a plausible treatment strategy in these tumors. Subprotocol Z1C of the NCI-Molecular Analysis for Therapy Choice trial was designed to evaluate the CDK4/6 inhibitor palbociclib in CDK4- or CDK6-amplified tumors. Patients and Methods: Patients had a solid malignancy or lymphoma with progression on at least one systemic therapy for advanced disease or with no standard-of-care therapy available. Tumors with ≥7 copies of CDK4 or CDK6 were considered amplified and molecularly eligible. Enrolled patients were treated with palbociclib 125 mg daily on days 1 to 21 of a 28-day cycle. The primary endpoint was objective response rate. Results: Forty-three patients were enrolled on subprotocol Z1C, and 38 patients were deemed eligible, treated, and included in analyses; 25 patients were eligible, treated, and centrally confirmed to have CDK4 or CDK6 amplification and comprised the primary analysis cohort for objective response rate endpoint. Among the 25 patients in the primary cohort, one patient had a partial response, 4 patients had stable disease, and 16 patients had progressive disease as best response. Four patients were not evaluable due to lack of follow-up scans. Among the 38 evaluable patients, one patient had a partial response, 10 patients had stable disease, and 21 patients had progressive disease as best response. Partial response and stable disease were seen only in patients with CDK4 amplification. Median progression-free survival was 2.0 months, and median overall survival was 8.8 months. Conclusions: Palbociclib showed limited activity in histology-agnostic CDK4- or CDK6-amplified tumors, although central nervous system tumors may be worthy of future investigation. ©2024 American Association for Cancer Research. |
| Keywords: | adult; clinical article; human tissue; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; gene mutation; overall survival; genetics; clinical trial; fatigue; neutropenia; squamous cell carcinoma; diarrhea; drug efficacy; hypophosphatemia; systemic therapy; pyridines; follow up; anorexia; neoplasm; neoplasms; gene; progression free survival; multiple cycle treatment; phase 2 clinical trial; gene amplification; anemia; protein kinase inhibitor; leukopenia; nausea; thrombocytopenia; vomiting; cohort analysis; creatinine; tumor biopsy; pathology; abdominal pain; adrenal cortex carcinoma; lymphocytopenia; rash; protein kinase inhibitors; lung tumor; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; hyponatremia; skin tumor; glioblastoma; acne; muscle weakness; sepsis; hyperbilirubinemia; piperazines; kaplan meier method; gene dosage; leiomyosarcoma; drug therapy; piperazine derivative; head and neck tumor; cyclin dependent kinase 4; race; pyridine derivative; cyclin-dependent kinase 4; cyclin dependent kinase 6; copy number variation; cyclin-dependent kinase 6; gastrointestinal tumor; response evaluation criteria in solid tumors; high throughput sequencing; cdk4 gene; very elderly; cdk4 protein, human; objective response rate; humans; human; male; female; article; palbociclib; ecog performance status; cdk6 protein, human; cdk6 gene |
| Journal Title: | Clinical Cancer Research |
| Volume: | 31 |
| Issue: | 1 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2025-01-01 |
| Start Page: | 56 |
| End Page: | 64 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-24-0036 |
| PUBMED: | 39437014 |
| PROVIDER: | scopus |
| PMCID: | PMC11721435 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
