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Phase II Study of Palbociclib in Patients with Tumors with CDK4 or CDK6 Amplification: Results from the NCI-MATCH
Mark H O'Hara1, Opeyemi Jegede2, Mark A Dickson3
1Abramson Cancer Center at the University of Pennsylvania, Philadelphia, Pennsylvania.
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.
Insights
Palbociclib showed limited efficacy in treating advanced solid tumors with CDK4 or CDK6 amplification. Further investigation into central nervous system tumors is warranted.
Area of Science:
- Oncology
- Molecular Biology
- Clinical Trials
Background:
- Cyclin-dependent kinase 4 (CDK4) and CDK6 amplification is observed in various cancers.
- CDK4/6 inhibition presents a potential therapeutic strategy for these malignancies.
Purpose of the Study:
- To evaluate the efficacy of the CDK4/6 inhibitor palbociclib in patients with CDK4 or CDK6-amplified tumors.
- This study was conducted as part of the NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) trial, subprotocol Z1C.
Main Methods:
- Patients with advanced solid malignancies or lymphoma, with documented CDK4 or CDK6 amplification (≥7 copies), were enrolled.
- Eligible patients received palbociclib 125 mg daily for 21 days in a 28-day cycle.
- The primary endpoint was the objective response rate (ORR).
Main Results:
- Of 38 evaluable patients, one partial response and 10 instances of stable disease were observed, with 21 experiencing progressive disease.
- In the primary cohort of 25 patients with confirmed amplification, one partial response and four stable disease cases occurred.
- Responses were exclusively observed in patients with CDK4 amplification. Median progression-free survival was 2.0 months and median overall survival was 8.8 months.
Conclusions:
- Palbociclib demonstrated limited activity in a broad range of CDK4/6-amplified solid tumors.
- Central nervous system tumors with CDK4/6 amplification may represent a subset for future therapeutic exploration.
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