For patients with pituitary tumors who have exhausted standard treatment protocols, there are few therapeutic options. It is those patients who were top of mind for Odelia Cooper, MD, and the Cedars-Sinai Pituitary Center team when they launched a research study to examine a cutting-edge pharmaceutical protocol initially pioneered in the oncological field.
Innovative prolactinoma tumor treatment at Cedars-Sinai
Odelia B. Cooper, MD
As an endocrinologist and associate professor at Cedars-Sinai, Cooper is accustomed to treating patients with pituitary tumors. For a patient with a typical prolactinoma, the current standard of treatment is dopamine agonist oral medications and surgery.
"Pituitary tumors are usually benign and respond well to these therapies," says Cooper, "but 10%-15% can be resistant to typical therapies. I was seeing a lot of these patients in clinic and realized we did not have a lot of options for escalating treatment once we had maximized their standard therapies."
The lack of further treatment options was distressing to patients, and Cooper wondered how the science might be advanced to improve outcomes for those resistant to current therapies. Cooper and the interdisciplinary team at the Cedars-SinaiPituitary Center are focused on delivering the most effective, tailored therapeutic options for their patients informed by the most recent research, and she believed there could be better options for patients who present with aggressive prolactinomas.
Building on research started in the oncological field that developed medications that target the epidermal growth factor receptor (EGFR) pathway, Cooper and her research partners identified a medication protocol that uses the same pathway to reduce prolactin and also inhibit aggressive prolactinoma growth.
"The EGFR pathway is well known to oncologists," explains Cooper. "They have developed an armamentarium of medications to target this pathway, but I realized the pathway was under-studied in the context of pituitary tumors."
For this research study, Cooper and her colleagues chose the drug lapatinib to test reduction in prolactin and tumor size. Lapatinib is a tyrosine kinase inhibitor (TKI) that targets the EGFR pathway and Erb-B2 receptor. Collaborating with postdoctoral researchers, they showed that the EGFR pathway was active and could be inhibited with TKIs in cellular and animal models of prolactinomas. Further, pituitary surgical colleagues assisted with careful collection of prolactinoma samples from patients who were not responding to traditional therapies.
"We collected tissue from human prolactinomas and saw that, with lapatinib, the prolactin levels went down. We confirmed that the EGFR pathway is indeed active in patients with prolactinoma tumors."
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From the bench to the bedside
With these findings, Cooper and her team began enrolling patients in a subsequent research trial to test the lapatinib protocol on patients. Because this type of aggressive prolactinoma is relatively rare and the inclusion criteria were extremely rigorous, enrollment numbers were small but achieved encouraging results.
With doses of lapatinib, 75% of trial enrollees achieved stabilization of their tumor. One participant underwent a 41% reduction in tumor volume.
"The results suggested that tyrosine kinase inhibitors like lapatinib can play a role in treating these rare, aggressive prolactinomas," says Cooper. "We successfully 'flattened the growth curve' of the tumor over the six months of the trial."
According to Cooper, these findings—and future positive outcomes for patients—are the result of the team-based care that is a cornerstone at Cedars-Sinai.
"While lapatinib is well tolerated, each physician has to work with their team to weigh the benefits and risks of the therapies and determine what the best course of action is for their patients," she adds.
At Cedars-Sinai 's Pituitary Center, the team is multidisciplinary, with leading surgeons, endocrinologists, radiation and neuro-oncologists and researchers all partnering to deliver the most effective therapies and treatments to their patients.
