Phase II Trial of Palbociclib in Patients with Advanced Esophageal or Gastric Cancer.

The Oncologist
Thomas B KarasicPeter J O'Dwyer

Abstract

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. 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. 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. 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. ...Continue Reading

References

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Aug 1, 2014·Nature·UNKNOWN Cancer Genome Atlas Research Network
Dec 17, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Angela DeMichelePeter O'Dwyer
Aug 17, 2017·Nature·Shom GoelJean J Zhao
Nov 5, 2017·Cancer Discovery·Jiehui DengKwok-Kin Wong
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Jan 12, 2019·Frontiers in Oncology·Francesco SchettiniLucia Del Mastro
Feb 6, 2019·Nature Genetics·Alexander M FrankellRebecca C Fitzgerald

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