In a single-institution study reported in the Journal of Clinical Oncology, Weitz et al found that the CDK4/6 inhibitor palbociclib was active as a novel treatment in patients with peritoneal mucinous carcinomatosis with GNAS mutation.
As stated by the investigators: “Mucinous neoplasms of the gastrointestinal tract are characterized by a propensity for metastasis to the peritoneum, resulting in … [peritoneal mucinous carcinomatosis]. A subset of these tumors, most often originating in the appendix, harbor mutations in the GNAS oncogene.
In the trial, 16 patients from the University of California, San Diego, received palbociclib starting at 125 mg once daily for 21 days, followed by a 7-day break, between August 2016 and June 2022. Of these, 12 had disease progression on at least one previous line of chemotherapy.
Key Findings
A reduction in carcinoembryonic antigen was observed in 13 (81%) of 16 patients, with a reduction > 50% in 6 (38%). As assessed by clinical and modified peritoneal Response Evaluation Criteria in Solid Tumors, 50% of patients had stable disease after 12 months of palbociclib.
Median progression-free survival was 84 months, with a 1-year rate of 56.2%. Median overall survival was not reached, with a 1-year rate of 81.2%.
Studies ex vivo showed that clinical response to CDK4/6 inhibition was reflected in tumors with GNAS mutation and mucinous histology.
The investigators concluded: “CDK4/6 inhibition with palbociclib had clinical activity in [peritoneal mucinous carcinomatosis] characterized by mutations in GNAS that was superior to that previously reported with cytotoxic chemotherapy. CDK4/6 inhibition is a novel therapeutic strategy worthy of further evaluation in this subgroup of gastrointestinal neoplasms.”
Andrew M. Lowy, MD, of the Department of Surgery, University of California, San Diego, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the Levine Family Chancellor’s Endowed Chair in Surgical Oncology, National Organization for Rare Disorders, and others. For full disclosures of the study authors, visit ascopubs.org.
