In 2013, the FDA granted pertuzumab combined with trastuzumab and docetaxel accelerated approval in patients with HER2-positive, locally advanced, inflammatory or early-stage breast cancer. The approval was based in part on data from the randomized, open-label, phase 2 NeoSphere trial.7
“In neoadjuvant studies you can get data much faster because the main outcome is simply whether the cancer disappeared when the patient got to surgery, or pathologic complete response,” Dr DeMichele said. “If pertuzumab gets more patients to a pathologic complete response in the neoadjuvant setting, the theory is that it would reduce the number of patients who relapse later.”
The rates of pathologic complete response, according to the FDA definition, were 39.3% in patients who received pertuzumab plus trastuzumab and docetaxel compared with 21.5% in patients who received trastuzumab plus docetaxel alone.
In its neoadjuvant approval of pertuzumab, the FDA said that after surgery, patients should receive 1 year of adjuvant trastuzumab to complete their treatment. Continued approval for pertuzumab in early-stage breast cancer was dependent on further demonstration of improvement in disease-free survival in a confirmatory trial.
“They wanted long-term studies to confirm that the increase in pathologic complete response as a surrogate endpoint was accurate and clinically meaningful,” Dr DeMichele said. “It is critical to link the surgical response to treatment to whether patients relapse after surgery.”