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Updated APHINITY Trial Data Show Addition of Pertuzumab to Trastuzumab Plus Chemotherapy Continues to Yield Clinical Benefit in Patients With Operable HER2-positive Early Breast Cancer

SAN ANTONIO — Data from six-year analysis of the APHINITY trial showed that adding pertuzumab to the previous standard of trastuzumab plus chemotherapy after surgery continued to reduce the risk of recurrence and death in patients with HER2-positive early breast cancer, according to data presented at the 2019 San Antonio Breast Cancer Symposium, held Dec. 10–14.

Fewer deaths were seen in patients treated with pertuzumab, although the survival benefit was not statistically significant at this time.

“The addition of trastuzumab to chemotherapy after surgery has revolutionized treatment outcomes for patients with HER2-positive early breast cancer, yet roughly 30 percent of patients will still experience recurrence of their disease, a condition for which effective treatments are now available but cure is no longer possible,” said Martine Piccart, MD, PhD, cofounder of Breast International Group and Scientific Director at the Institut Jules Bordet in Brussels. “By adding a different yet complementary HER2 inhibitor, pertuzumab, to this treatment regimen, we hope to further reduce the risk of recurrence and advanced disease in this patient population.”

Earlier results from the phase III APHINITY trial comparing pertuzumab or placebo added to the standard adjuvant chemotherapy plus trastuzumab in patients with operable HER2-positive early breast cancer have been previously reported. They showed that patients treated with pertuzumab had improved rates of estimated three-year invasive disease-free survival (IDFS; time from randomization up to recurrence or death) compared with those in the placebo arm (94.1 percent versus 93.2 percent, respectively). The addition of pertuzumab reduced the relative risk of recurrence by 19 percent, which was statistically significant. The overall survival (OS) did not significantly differ between the two arms in the earlier analysis. The current study reports on the six-year interim analysis of OS and an updated descriptive analysis of IDFS and cardiac safety.

Between November 2011 and August 2013, the APHINITY trial randomly assigned 2,400 patients to the pertuzumab arm and 2,405 patients to the placebo arm. The data cutoff for this updated OS analysis was June 19, 2019, corresponding to a median follow-up time of 74.1 months.

After six years of follow-up, Piccart and colleagues found in this descriptive analysis of IDFS that among the overall population, those in the pertuzumab arm had a reduced relative risk of breast cancer recurrence or death by 24 percent compared with the placebo arm.

Similar to their previous findings, Piccart and colleagues found that patients whose cancer had spread to their lymph nodes continued to derive greatest clinical benefit with the addition of pertuzumab to standard treatments. In the six-year updated analysis, the researchers found that, among patients with node-positive disease, the IDFS in the pertuzumab arm was 87.9 percent, while the IDFS in the placebo arm was 83.4 percent, representing a 4.5 percent improvement. The addition of pertuzumab to trastuzumab and chemotherapy after surgery translated to a reduced relative risk of recurrence by 28 percent in this cohort.

In this updated analysis, one additional primary cardiac event was reported in the pertuzumab arm, and one additional secondary cardiac event was reported in each arm; no new cardiac safety concerns emerged, noted Piccart. “Incidence of primary cardiac events remains less than 1 percent in both arms (0.8 percent in the pertuzumab arm versus 0.3 percent in the placebo arm), providing further evidence that adding pertuzumab to trastuzumab and chemotherapy is safe in the long term,” she said.

“Following this interim analysis, the evidence is now even stronger than adding pertuzumab to the previous standard of care reduces the risk of disease recurrence for patients with HER2-positive breast cancer,” said Piccart. “Altogether, the clinical benefit of pertuzumab, which is exemplified by its treatment effect against breast cancer and its lack of additional significant side effects, is enhanced for women at high risk of breast cancer recurrence in this curative setting.

“A main limitation of APHINITY is that although we have seen fewer deaths among the patients who received treatment with pertuzumab, our data is still immature and have not shown definitive improvement in overall survival. A longer follow-up is needed to see any significant survival benefit,” Piccart said. The next interim analysis is scheduled to take place in 2022.

“Ongoing research using the biological specimens and clinical data collected from this very large study would help in refining the characteristics of the patients who will most benefit from

pertuzumab, particularly among those considered to be at lower risk of recurrence only on the basis of absence of lymph node disease,” she added.

This study was supported by Roche.

Piccart has served as a consultant on the scientific advisory board at Roche, for which she has received honoraria. Additionally, Piccart is a consult for the advisory boards of AstraZeneca, Camel-IDS, Crescendo Biologics, Debiopharm, G1 Therapeutics, Huya Bioscience International, Immunomedics, Eli Lilly, The Menarini Group, Merck, Novartis, Odonate Therapeutics, PeriphaGen, Pfizer, and Seattle Genetics. She is a scientific board member for Oncolytics and Radius.

Piccart’s institution receives funding from Eli Lilly, Merck, Pfizer, Radius Health, Roche/Genentech, AstraZeneca, Novartis, Servier Pharmaceuticals, and Synthon Pharmaceuticals.