Long-Term Data Confirms One-Year of Adjuvant Trastuzumab as Standard of Care

Eight-year follow-up data from the phase III HERA trial has confirmed that 1-year of adjuvant trastuzumab (Herceptin) should remain the treatment standard in women with HER2-positive early-stage breast cancer. In the HERA study, extending trastuzumab therapy to 2 years did not produce an additional benefit. The long-term HERA results were presented at the 2012 European Society for Medical Oncology (ESMO) Congress and again at the 35th Annual San Antonio Breast Cancer Symposium (SABCS).

“You gain nothing from adding the additional year of Herceptin,” said Brian Leyland-Jones, MBBS, PhD, in an interview with OncLive.com at SABCS. “One-year of trastuzumab is now a proven advantage from both a disease-free survival and overall survival viewpoint,” added Leyland-Jones, who is director of Edith Sanford Breast Cancer Research, Sioux Falls, South Dakota, and one of the authors of the HERA study.

HERA accrued 5102 women with locally determined HER2-positive invasive early breast cancer between 2001 and 2005. In a press conference at SABCS, Martine J. Piccart, MD, PhD, chief of the Medicine Department at the Jules Bordet Institute in Brussels, Belgium, president of ESMO, and chair of the Breast International Group, said, “HER2 status had to be centrally confirmed [IHC 3 positive or FISH positive] prior to randomization.”

Following surgery and physician-determined treatment with chemotherapy and/or radiotherapy, patients were randomized to 1 year of trastuzumab (n = 1703), 2 years of trastuzumab (1701), or observation (1698). Trastuzumab therapy in both treatment arms consisted of an 8 mg/kg loading dose followed by 6 mg/kg every 3 weeks.

After the initial HERA results were presented at the 2005 ASCO Annual Meeting, patients in the observation arm were given the option to receive trastuzumab. “In 2005, after the release of the strikingly positive results in this trial and two other trials conducted in the United States, 52% of the women randomized to the observation arm selectively crossed over to receive trastuzumab,” Piccart said.

At 8 years’ median follow-up, disease-free survival (DFS) and overall survival (OS) were similar between the 1- and 2-year treatment arms. The unadjusted hazard ratio (HR) for a DFS event in the longer versus shorter trastuzumab arms was 0.99 (95% CI, 0.85-1.14; P = .86). With the OS comparison, the HR was 1.05 (95% CI, 0.86-1.28; P = .63).

Piccart said hormone-receptor status did not affect the efficacy of the treatment. “Women with HER2-positive breast cancer benefited from trastuzumab whether they had hormone-receptor positive tumors or hormone-receptor negative tumors.”

The primary cardiac endpoint of symptomatic congestive heart failure was rare and did not vary greatly between the two treatment arms. However, rates of the secondary cardiac endpoint of asymptomatic cardiac dysfunction were higher with 2 versus 1 year of trastuzumab at 7.2% and 4.1%, respectively. Importantly, Piccart noted that treatment cessation mostly eliminated cardiotoxicity. “Very few women experienced any cardiac event after stopping adjuvant trastuzumab,” Piccart said. “Most of the cardiac events in HERA, like in the other adjuvant trials of trastuzumab, have been reversible.”

With the 1-year trastuzumab regimen now established, Kent Osborne, MD, commented at the SABCS press conference about the cost implications of the HERA results. “I think the HERA trial is an extremely important one. The reason it’s so important is that you can imagine the cost to healthcare if we had to give trastuzumab for 2 years rather than 1. So I was really gratified to see that one year seems to be just as good,” said Osborne, who is director of the Dan L. Duncan Cancer Center and the Lester and Sue Smith Breast Center at Baylor College of Medicine in Houston, Texas.

Going forward, Leyland-Jones said the next challenge will be determining the optimal treatment duration of trastuzumab in combination regimens. “We think that we’ve hit the gold standard in terms of [treatment length] of Herceptin as monotherapy. How this could change is when you have combinations. So when you have trastuzumab plus pertuzumab or when you start adding PI3 kinase inhibitors or other drugs, then I think this whole duration question is going to come up again.”

SOURCE: OncLive