The clinical trial results, publishing in the October 16, 2024 online edition of the Journal of Clinical Oncology, showed the oral medication, known as palbociclib, stabilized tumor growth and reduced blood tumor marker levels in patients with peritoneal mucinous carcinomatosis (PMC). This form of cancer originates in the appendix and is often resistant to standard chemotherapy.

“Finding that a breast cancer drug is successful in treating a subset of appendix cancer — where treatment options are currently limited — marks a significant advancement in our fight against this disease,” said co-senior author Andrew Lowy, MD, professor in the Department of Surgery and chief of the Division of Surgical Oncology at UC San Diego School of Medicine and clinical director for cancer surgery at Moores Cancer Center at UC San Diego Health. “This breakthrough introduces the first targeted therapy for this rare cancer.”

Appendix cancer is extremely uncommon, accounting for less than 1% of all gastrointestinal cancers, with the American Cancer Society estimating fewer than 2,000 cases diagnosed in the U.S. each year.

The study cohort involved 16 participants diagnosed with PMC, most of whom had previously received other treatments without success. Researchers analyzed the genetic mutations present within these cancers and found that tumors with mutations in one specific gene, GNAS, responded well to the drug. In these patients, blood markers associated with cancer activity were reduced in more than 80% of patients.

Laboratory results also showed that the drug slowed or stopped the multiplication of cancer cells, offering a well-tolerated alternative to chemotherapy, which is often associated with severe side effects.

“This medication can be implemented immediately without the need to wait for a new drug to be developed or for FDA approval,” said co-senior author Shumei Kato, MD, associate professor of medicine at UC San Diego School of Medicine and medical oncologist at UC San Diego Health.

Kato, who is also a UC San Diego Moores Cancer Center member, adds that the study underscores the advanced use of existing cancer treatments.

“The findings signal a promising new era for the treatment of appendix cancer and potentially other rare cancers with similar genetic mutations.”

Next steps include investigating how combining this drug with both traditional chemotherapies and newer targeted therapies could further enhance its effectiveness.

“This groundbreaking study validates our unique position as the only National Cancer Institute (NCI)-designated Comprehensive Center in the region and our commitment to discovering and offering the most leading-edge treatment options,” said Diane Simeone, MD, director of Moores Cancer Center at UC San Diego Health. “As an academic medical center, our clinical researchers are leading trials that are identifying promising new treatments and providing hope for patients who previously had few options.”

Co-authors of the study include: Jonathan Weitz, Daisuke Nishizaki, Joy Liau, Jay Patel, Isabella Ng, Siming Sun, Dana Ramms, Jingjing Zou, Brian Wishart, Jordan Rull, Joel Baumgartner, Kaitlyn Kelly, Rebekah White, Jula Veerapong, Mojgan Hosseini, Hitendra Patel, Gregory Botta, Silvio Gutkind, and Herve Tiriac, all at UC San Diego.

Funding support for the study came, in part, by grants from the Levine Family Chancellor’s Endowed Chair in Surgical Oncology, National Organization for Rare Disorders, Appendix Cancer Pseudomyxoma Peritonei Research Foundation (R21CA273974, 1F32CA265052-01) and generous gifts from the estate of Elisabeth and Ad Creemers, the Euske Family Foundation, the Gastrointestinal Cancer Research Fund and the Peritoneal Metastasis Research Fund. Confocal imaging and histology core done with support from the UC San Diego Health Specialized Cancer Support Center (P30 2P30CA023100).