(UPDATE) Pertuzumab in Breast Cancer
Updated: Friday, May 3, 2019
Since the initial approvals for pertuzumab (Perjeta) in the treatment of metastatic1 and neoadjuvant2 HER2-positive breast cancers in 2012 and 2013 (see Original Pertuzumab Spotlight), this agent may now also be used in combination with trastuzumab and chemotherapy in the adjuvant setting.3 Based on data from the APHINITY trial (ClinicalTrials.gov identifier: NCT01358877),4 patients with HER2-positive early-stage breast cancer at high risk of recurrence may be treated with pertuzumab as part of an adjuvant regimen.
In July 2017, the APHINITY trial showed that pertuzumab “significantly improved the rates of invasive disease–free survival among patients with HER2-positive, operable breast cancer when it was added to trastuzumab and chemotherapy.”4
In 2018, the results of the PERTAIN trial5 indicated that pertuzumab can be safely incorporated into treatment for patients with so-called triple-positive locally advanced or metastatic breast cancer. Specifically, patients with hormone receptor–positive and HER2-positive disease may receive an aromatase inhibitor plus the combination of trastuzumab and pertuzumab.
To view the latest updates on pertuzumab in the treatment of patients with breast cancer, see the NCCN Clinical Practice Guidelines in Oncology for Breast Cancer.6
- FDA approves Perjeta for type of late-stage breast cancer. Available at: http://www.rxlist.com/script/main/art.asp?articlekey=159228. Accessed April 22, 2019.
- FDA approves Perjeta for neoadjuvant breast cancer treatment. Available at: https://www.healio.com/hematology-oncology/breast-cancer/news/online/%7Bdab37533-584a-467f-9d94-facc87e73747%7D/fda-approves-perjeta-for-neoadjuvant-breast-cancer-treatment. Accessed April 22, 2019.
- Howie LJ, Scher NS, Amiri-Kordestani L, et al. FDA approval summary: pertuzumab for adjuvant treatment of HER2-positive early breast cancer [published online December 14, 2018]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-18-3003].
- von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med 2017;377:122–131.
- Rimawi M, Ferrero JM, de la Haba-Rodriguez J, et al. First-line trastuzumab plus an aromatase inhibitor, with or without pertuzumab, in human epidermal growth factor receptor 2–positive and hormone receptor–positive metastatic or locally advanced breast cancer (PERTAIN): a randomized, open-label phase II trial. J Clin Oncol 2018;36:2826–2835.
- Gradishar WJ, Anderson BO, Balassanian R, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Breast Cancer. Version 1.2019. Accessed April 22, 2019. To view the most recent version of these guidelines, visit NCCN.org.
Commentary by Breast Cancer Site Editor for JNCCN 360
William J. Gradishar, MD
Director, Clinical Network; Chief, Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago
Expanding treatment options for women with HER2-positive breast cancer have improved outcomes for patients with both early- and late-stage disease. The incorporation of pertuzumab into neoadjuvant regimens and its use in the adjuvant setting has clearly “moved up” the use of pertuzumab to early-stage disease, in contrast to accepted practice just a few years ago, when pertuzumab was used solely in the metastatic disease setting. The finding that the pathologic complete response rate could be enhanced with the use of pertuzumab added to trastuzumab and chemotherapy in the preoperative setting ultimately improved overall long-term outcomes and laid the foundation for the findings ultimately confirmed in the APHINITY trial. That said, there are patients with HER2-positive early-stage breast cancer who may not require adjuvant pertuzumab.
The APHINITY trial showed that the greatest benefit derived from pertuzumab was in patients with node-positive disease and those with estrogen receptor–negative disease. However, there are lower-risk patients, particularly those with small, node-negative HER2-positive disease who may be treated with trastuzumab and paclitaxel with the expectation that their long-term outcomes will be excellent.
The implication of wider use of pertuzumab in early-stage breast cancer is that for those patients who do develop a recurrence, the use of other agents, such as ado-trastuzumab emtansine (T-DM1), moves up in the algorithm for treating metastatic disease. Fortunately, numerous new agents targeting the HER2 pathway continue to be developed and should expand the therapeutic options available to clinicians and patients.
Dr. Gradishar has received clinical research support or served on a data safety monitoring board for Genentech, Inc. He also has served on a scientific advisory board or as a consultant or expert witness for AstraZeneca Pharmaceuticals LP, Genentech, Inc., Merck & Co., Inc., and Pfizer, Inc.