TY - JOUR
T1 - Phase II Study of Palbociclib (PD-0332991) in CCND1, 2, or 3 Amplification
T2 - Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1B
AU - Clark, Amy S.
AU - Hong, Fangxin
AU - Finn, Richard S.
AU - DeMichele, Angela M.
AU - Mitchell, Edith P.
AU - Zwiebel, James
AU - Arnaldez, Fernanda I.
AU - Gray, Robert J.
AU - Wang, Victoria
AU - McShane, Lisa M.
AU - Rubinstein, Larry V.
AU - Patton, David
AU - Williams, P. Mickey
AU - Hamilton, Stanley R.
AU - Copur, Mehmet S.
AU - Kasbari, Samer S.
AU - Thind, Ravneet
AU - Conley, Barbara A.
AU - Arteaga, Carlos L.
AU - O’Dwyer, Peter J.
AU - Harris, Lyndsay N.
AU - Chen, Alice P.
AU - Flaherty, Keith T.
N1 - Publisher Copyright:
© 2023 The Authors; Published by the American Association for Cancer Research.
PY - 2023/4
Y1 - 2023/4
N2 - Purpose: Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, the gene encoding cyclin D, is known to be amplified in a variety of solid tumors. Palbociclib is an oral CDK4/6 inhibitor, approved in advanced breast cancer in combination with endocrine therapy. We explored the efficacy of palbociclib in patients with nonbreast solid tumors containing an amplification in CCND1, 2, or 3. Patients and Methods: Patients with tumors containing a CCND1, 2, or 3 amplification and expression of the retinoblastoma protein were assigned to subprotocol Z1B and received palbociclib 125 mg once daily for 21 days of a 28-day cycle. Tumor response was assessed every two cycles. Results: Forty patients were assigned to subprotocol Z1B; 4 patients had outside assays identifying the CCND1, 2, or 3 amplification and were not confirmed centrally; 3 were ineligible and 2 were not treated (1 untreated patient was also ineligible), leaving 32 evaluable patients for this analysis. There were no partial responses; 12 patients (37.5%) had stable disease as best response. There were seven deaths on study, all during cycle 1 and attributable to disease progression. Median progression-free survival was 1.8 months. The most common toxicities were leukopenia (n ¼ 21, 55%) and neutropenia (n ¼ 19, 50%); neutropenia was the most common grade 3/4 event (n ¼ 12, 32%). Conclusions: Palbociclib was not effective at treating nonbreast solid tumors with a CCND1, 2, or 3 amplification in this cohort. These data do not support further investigation of single-agent palbociclib in tumors with CCND1, 2, or 3 amplification.
AB - Purpose: Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, the gene encoding cyclin D, is known to be amplified in a variety of solid tumors. Palbociclib is an oral CDK4/6 inhibitor, approved in advanced breast cancer in combination with endocrine therapy. We explored the efficacy of palbociclib in patients with nonbreast solid tumors containing an amplification in CCND1, 2, or 3. Patients and Methods: Patients with tumors containing a CCND1, 2, or 3 amplification and expression of the retinoblastoma protein were assigned to subprotocol Z1B and received palbociclib 125 mg once daily for 21 days of a 28-day cycle. Tumor response was assessed every two cycles. Results: Forty patients were assigned to subprotocol Z1B; 4 patients had outside assays identifying the CCND1, 2, or 3 amplification and were not confirmed centrally; 3 were ineligible and 2 were not treated (1 untreated patient was also ineligible), leaving 32 evaluable patients for this analysis. There were no partial responses; 12 patients (37.5%) had stable disease as best response. There were seven deaths on study, all during cycle 1 and attributable to disease progression. Median progression-free survival was 1.8 months. The most common toxicities were leukopenia (n ¼ 21, 55%) and neutropenia (n ¼ 19, 50%); neutropenia was the most common grade 3/4 event (n ¼ 12, 32%). Conclusions: Palbociclib was not effective at treating nonbreast solid tumors with a CCND1, 2, or 3 amplification in this cohort. These data do not support further investigation of single-agent palbociclib in tumors with CCND1, 2, or 3 amplification.
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U2 - 10.1158/1078-0432.CCR-22-2150
DO - 10.1158/1078-0432.CCR-22-2150
M3 - Article
C2 - 36853016
AN - SCOPUS:85152595381
SN - 1078-0432
VL - 29
SP - 1477
EP - 1483
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 8
ER -