Three-drug cocktail of targeted therapies promising against hormone receptor and HER2 positive metastatic breast cancer

The growth of some breast cancers is driven by hormones like estrogen and progesterone. Other breast cancers are driven by changes in the gene HER2. Still some cancers are driven by both – and breast cancers whose growth can be controlled by hormonal receptors and HER2 can be especially tricky to treat. A University of Colorado Cancer Center phase 1b study presented at the American Society for Clinical Oncology (ASCO) Annual Meeting 2019 offers an attractive alternative to the chemotherapy that is often used with these patients: the three-drug cocktail of targeted treatments – tucatinib, palbociclib and letrozole – was overall well-tolerated and showed preliminary evidence of promising anti-cancer activity. Results support the continued development of the combination in an ongoing phase 2 clinical trial.

“I see this as a promising chemotherapy-free combination for patients who have been without good options, especially for those whose disease has spread to the brain,” says Elena Shagisultanova, MD, PhD, investigator at CU Cancer Center and the trial’s principal investigator.

Tucatinib is a targeted HER2 inhibitor; palbociclib stops cancer cells from rushing through the cell cycle required for fast proliferation; and the anti-hormonal drug letrozole restricts the ability of cancers to drive growth using estrogens. Previous work has shown that palbociclib and letrozole combine to kill more cancer cells than letrozole alone. And lab work by Shagisultanova and her mentor Virginia Borges, MD, at CU Cancer Center led them to believe that tucatinib should be a potent addition to this combination.

Results of the current trial show that the theory holds up in humans: of 20 patients enrolled on the study since November 2018, 14 remained on study as of 1/4/2019, five of which had been on the study more than 6 months. The goal of the phase 1b study was to explore the safety of this combination, with no patients experiencing side effects that required study withdrawal.

“All these patients have metastatic breast cancer and up to five different treatments before trying this trial. Also, 45 percent have brain metastases. In this population, our results look promising,” Shagisultanova says.

A phase 2 trial further exploring the combination is offered at CU Cancer Center, University of Arizona, Northwestern University, New Mexico Cancer Care Alliance, Stony Brook University, and University of Texas Health Science Center San Antonio.