Open AccessPhase II Trial of Palbociclib in Patients with Advanced Esophageal or Gastric Cancer
Author(s) -
Karasic Thomas Benjamin,
O'Hara Mark H.,
Teitelbaum Ursina R.,
Damjanov Nevena,
Giantonio Bruce J.,
d'Entremont Tracy S.,
Gallagher Maryann,
Zhang Paul J.,
O'Dwyer Peter J.
Publication year - 2020
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2020-0681
Subject(s) - palbociclib , medicine , cancer , gastroenterology , esophageal cancer , oncology , cyclin dependent kinase , neutropenia , adenocarcinoma , phases of clinical research , clinical endpoint , clinical trial , cell cycle , chemotherapy , breast cancer , metastatic breast cancer
Lessons Learned Palbociclib monotherapy demonstrated minimal clinical activity in patients with previously treated gastroesophageal cancers. Further clinical evaluation of palbociclib monotherapy is not warranted in gastroesophageal cancers, but improved understanding of resistance mechanisms may permit rational combination approaches.Background Dysregulation of the cell cycle is a hallmark of cancer. Progression through the G1/S transition requires phosphorylation of retinoblastoma (RB) by cyclin‐dependent kinases (CDKs) 4 and 6, which are regulated by cyclins D and E. Amplifications of cyclin D loci and activating mutations in CDKs are frequent molecular aberrations in gastroesophageal malignancies. We conducted a phase II trial of the CDK4/6 inhibitor palbociclib as an initial test of efficacy. Methods Patients with previously treated metastatic gastroesophageal cancers with intact RB nuclear expression by immunohistochemistry were treated with 125 mg daily of palbociclib for days 1–21 of 28‐day cycles. The primary endpoint was overall response rate. Results We screened 29 patients and enrolled 21 patients: 5 with gastric adenocarcinoma, 3 with gastroesophageal junction adenocarcinoma, 8 with esophageal adenocarcinoma, and 5 with esophageal squamous cell carcinoma. All 29 tumors screened had intact nuclear RB expression, and four treated patients tested positive for CCND1 overexpression. No objective responses were seen. Median progression‐free survival was 1.8 months, and median overall survival was 3.0 months. All recurrent grade 3 or 4 toxicities were hematologic, with neutropenia in eight patients (38%), anemia in four patients (19%), and thrombocytopenia in two patients (10%). Conclusion Palbociclib has limited single‐agent activity in gastroesophageal tumors.