Adam Brufsky, MD, PhD
The recent approval of pertuzumab (Perjeta) as part of a combination neoadjuvant treatment for patients with early-stage breast cancer has paved the way for wider use of the regimen in preoperative settings, experts indicated during a recent Peer Exchange panel discussion.
In September 2013, the FDA approved pertuzumab in combination with trastuzumab (Herceptin) and chemotherapy for patients with HER2-positive locally advanced or early-stage breast cancer, marking the first neoadjuvant indication in that disease setting. This accelerated approval was based on results from the phase II NeoSphere trial,1 which showed that pertuzumab, a HER dimerization inhibitor, combined with the HER2 inhibitor trastuzumab and the chemotherapy docetaxel, significantly improved pathologic complete response (pCR) when compared with three other neoadjuvant regimens. In the study, pCR was defined as the absence of invasive cancer in the breast and lymph nodes.
In a recent OncLive
Peer Exchange roundtable entitled “Practical Considerations in Breast Cancer,” moderator Adam M. Brufsky, MD, PhD, Medical Director, Women’s Cancer Center, Magee-Womens Hospital of UPMC, University of Pittsburgh Cancer Institute, asked panelists which patients they would consider for neoadjuvant therapy in HER2-positive breast cancer, based on the recent approval.
Denise A. Yardley, MD
“In my own practice, I’ve actually lowered the bar of what I would have traditionally considered a patient who was locally advanced with a large tumor involvement of the skin or bulky axillary nodes almost to tumors that I think are eligible for adjuvant therapy,” replied Denise A. Yardley, MD, Senior Investigator, Breast Cancer Research, Sarah Cannon Research Institute, Tennessee Oncology. “From our own practice, I think tumors that have any degree of evidence of nodal involvement or tumors—if we look at size—we have some T1 tumors that are applicable for neoadjuvant strategies.”
In the phase II NeoSphere trial,1
417 patients with newly diagnosed HER2-positive early-stage breast cancer were evenly randomized to one of four treatment arms: trastuzumab plus docetaxel (n = 107, group A), pertuzumab and trastuzumab plus docetaxel (n = 107, group B), pertuzumab plus trastuzumab (n = 107, group C), or pertuzumab plus docetaxel (n = 96, group D).
Patients who received pertuzumab/trastuzumab/ docetaxel experienced a significant improvement in pCR of 45.8% (95% CI, 36.1-55.7), compared with 29% (95% CI, 20.6-38.5), 24% (95% CI, 15.8-33.7), and 16.8% (95% CI, 10.3-25.3) for groups A, D, and C, respectively.
The most common grade 3 severity or higher adverse events (AEs) observed in the pertuzumab/ trastuzumab/docetaxel arm were neutropenia (48 of 107), febrile neutropenia (9 of 107), and leukopenia (5 of 107). The number of serious AEs was similar in groups A, B, and D, but was much lower in group C, which did not receive chemotherapy.
Joyce A. O’Shaughnessy, MD
The indication for pertuzumab specifies that it should be used in patients with node-positive T2 breast cancer. However, given the magnitude of benefit with administration of the drug, the panelists said it might be appropriate to treat patients with HER2-positive T2 N0 or T1 N1 tumors.
“What I’ve been doing in my practice is trying to get people on it because that pathologic CR rate is so important, particularly in the ER [estrogen receptor]–negative, where we know it does translate into benefit,” explained Joyce A. O’Shaughnessy, MD, Chair, Breast Cancer Research, Baylor Charles A. Sammons Cancer Center, Texas Oncology and US Oncology. “I think if they meet the label, T2 N0 or node positive clinically by however you get there, they should pertuzumab preoperative.”