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Adjuvant pertuzumab offers modest benefit for HER-2-positive breast cancer
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CHICAGO — The addition of pertuzumab to adjuvant chemotherapy with trastuzumab demonstrated a significant, although modest, invasive DFS improvement for women with HER-2–positive breast cancer, according to results from the phase 3 APHINITY clinical trial presented at the ASCO Annual Meeting.
“Our early findings suggest that we may be able to further improve outcomes for some women by adding second HER-2–targeted treatment, without increasing risk for serious side effects,” Gunter von Minckwitz, MD, PhD, president of the German Breast Group in Neu-Isenburg, Germany, said during a press conference.
Although trastuzumab (Herceptin, Genentech) targets only HER-2, pertuzumab (Perjeta, Genentech) also blocks HER-2 and HER-3. Using both of these antibodies may more completely block cancer cell growth signals and lower the chance of treatment resistance.
von Minckwitz and colleagues randomly assigned 4,805 women with HER-2–positive breast cancer to receive standard adjuvant chemotherapy plus 1 year of trastuzumab plus pertuzumab (n = 2,400) or placebo (n = 2,405). All patients received treatment 8 weeks following mastectomy or lumpectomy.
Sixty-three percent of patients had node-positive disease, 36% had hormone receptor–negative disease and all had tumor size larger than 1 cm.
Invasive DFS served as the primary efficacy endpoint.
The researchers predicted 3-year invasive DFS would be 91.8% for patients treated with pertuzumab and 89.2% for patients treated with placebo after 379 events (HR = 0.75).
Most patients completed treatment (pertuzumab, 84.5%; placebo, 87.4%).
Overall, invasive DFS events occurred in 171 patients treated with pertuzumab and 210 patients treated with placebo (7.1% vs. 8.7%; HR = 0.81; 95% CI 0.68-1).
Researchers reported 3-year invasive DFS rates of 94.1% in the pertuzumab arm and 93.2% in the placebo arm.
Patients with node-positive disease had a 3-year invasive DFS rate of 92% with pertuzumab and 90.2% with placebo (HR = 0.77; 95% CI, 0.62-0.96). However, the benefit did not persist with pertuzumab among women with node-negative disease (97.5% vs. 98.4%; HR = 1.13; 95% CI 0.68-1.86).
“Treatment effect was homogenous throughout all subgroups. However, the node-positive and hormone receptor–negative cohorts appeared to derive most benefit at the current point of time, with a 3-year invasive DFS increase of 1.8% and 1.6%, respectively,” von Minckwitz said.
The safety profile of pertuzumab appeared consistent with previous trials, von Minckwitz said.
Primary cardiac endpoints of heart failure and cardiac death occurred in 0.7% of patients in the pertuzumab arm and 0.3% of patients in the placebo arm. Secondary cardiac endpoints of asymptomatic or mildly symptomatic left ventricular ejection fraction decline also appeared similarly low (pertuzumab, 2.7%; placebo, 2.8%).
Grade 3 or worse diarrhea occurred more frequently among patients treated with pertuzumab than placebo (9.8% vs. 3.7%).
“Incidence of diarrhea was increased in the pertuzumab arm and occurred predominantly during chemotherapy with [docetaxel, carboplatin and trastuzumab],” von Minckwitz said.
“Given that the absolute benefit from adding pertuzumab was modest, we should consider using it primarily in women with the highest risk; those with node-positive and hormone receptor–negative breast cancer,” von Minckwitz added.
“APHINITY is a step forward in the treatment of HER-2–positive breast cancer and the relatively narrow benefits in numerical terms seen reflect the overall good prognosis,” Harold J. Burstein, MD, PhD, FASCO, senior physician at Dana-Farber Cancer Institute, associate professor of medicine at Harvard Medical School and ASCO expert, said during the press conference. – by Melinda Stevens
Reference:
von Minckwitz G, et al. Abstract LBA500. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosure: von Minckwitz reports research funding to his institution from AbbVie, Amgen, AstraZeneca, Celgene, Myriad Genetics, Novartis, Pfizer, Roche, Sanofi, Teva and Vifor Pharma. Please see the abstract for a list of all other researchers’ relevant financial disclosures.
Perspective
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Angela DeMichele, MD, MSCE
There is a very small benefit to adding pertuzumab (Perjeta, Genentech) to treatment for all patients, with clear financial and toxicity costs. The benefit is even smaller in the node-negative, lower-risk patients. Although statistically significantly better, we have to ask ourselves as a field if it is worth it, and carefully counsel patients.
There also are the data from the ExteNET study for neratinib (PB272, Puma Biotechnology), showing benefit in about 2% of patients. However, this it is a different decision because it takes therapy out to 2 years and is associated with a lot of diarrhea, so it is much less appealing to patients.
At the end of the day, we need to figure out biologically who the small subset of HER-2–positive patients (< 10%) are who fail our standard therapies. The best way to do that is in the neoadjuvant setting, in which we can study the biology of these resistant tumors and find drugs that overcome this resistance. Moreover, the vast majority of patients do really well, and some could undoubtedly do well with even less than standard therapy.
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