Francisco J. Esteva, MD, PhD
Although 6 months of adjuvant trastuzumab (Herceptin) demonstrated noninferiority to the standard 12 months in the phase III PERSEPHONE trial, Francisco J. Esteva, MD, PhD, said that it is unlikely to instantly shift the standard in the context of other clinical trials that have failed to demonstrate the same outcome.
In the trial, 4088 patients with HER2-positive early breast cancer were randomized to receive trastuzumab for 6 months (n = 2043) or 12 months (n = 2045). The 4-year disease-free survival rate at a 5-year follow-up was 89.8% and 89.4% with the 12-month and 6-month schedules, respectively (HR, 1.07; 90% CI, 0.93-1.24; P
Although the 6-month schedule cut the incidence of cardiac toxicity in half, Esteva maintained that “until we have all of the information, 1 year of therapy will remain the standard of care for most patients in the United States.”
In an interview at the 2018 OncLive®
State of the Science Summit™ on Breast Cancer, Esteva, medical oncologist, New York University’s Perlmutter Cancer Center, discussed recent advances and clinical findings with HER2-targeted therapies across the neoadjuvant, adjuvant, and metastatic settings.
OncLive: What are the improvements and advances in HER2-targeted therapy?
: There are some important data in the adjuvant setting for trastuzumab. [In my presentation], I also touched on some of the new therapies that are being explored in the metastatic setting.
In the adjuvant setting, one of the most important studies was a large randomized trial from the United Kingdom in which patients were either given the standard 1 year of trastuzumab or 6 months following surgery. Over 4000 patients were enrolled, so it was a reasonable sample size. Overall, they showed noninferiority for 6 months of therapy as opposed to 1 year of therapy. The question is how that fits into the standard of care. Should we give less [than 1 year of trastuzumab] based on the results of the trial?
This [question should be answered] in the context of other trials from France, Finland, and other places in which it was not clear that 6 months is as effective as 1 year of trastuzumab. Until we have all of the information, 1 year of therapy will remain the standard of care for most patients in the United States.
There is also interest in the development of trastuzumab biosimilars, which will hopefully reduce the cost of therapy in the future. One of the trials I was involved with compared trastuzumab to a trastuzumab biosimilar. We showed that the pathologic complete response in the neoadjuvant setting was the same for both drugs. We provided additional information at the 2018 ASCO Annual Meeting regarding the efficacy and safety of one of these biosimilars (CT-P6).
I also mentioned an update on the ExteNET trial, which looked at the use of neratinib (Nerlynx) in early-stage breast cancer after completing 1 year of trastuzumab. The ExteNET study showed an improvement in disease-free survival, especially in patients with estrogen receptor–positive disease compared with no additional therapy. At the 2018 ASCO Annual Meeting, there was a poster showing that the earlier you begin therapy, the better the results were in the randomized trial.