Shorter trastuzumab course may be viable for some women with early HER2-positive breast cancer

MUNICH — A 9-week course of adjuvant trastuzumab offered the same DFS benefit but with less cardiac toxicity than a 1-year course for women with small HER2-positive breast tumors, according to study results presented at European Society for Medical Oncology Congress.

The 1-year course should remain the standard for this population; however, the results show the shorter course could be viable in some cases, researchers concluded.

Guidelines for standard adjuvant treatment of HER2-positive early breast cancer recommend 1 year of anti-HER2 antibody therapy. This is based on the treatment duration used in registration trials.

However, there has been interest in the research community to determine if a shorter course of trastuzumab (Herceptin, Genentech) could achieve similar efficacy with reduced side effects and lower costs.

In the Short-HER trial, researchers randomly assigned 1,254 patients with early HER2-positive breast cancer to chemotherapy plus either 9 weeks or 1 year of trastuzumab.

After median follow-up of 6 years, the shorter course did not achieve noninferiority; however, it was associated with a lower rate of severe cardiac toxicity.

At ESMO, researchers presented results of an analysis designed to determine whether the shorter course may be noninferior to the longer course among certain patient subgroups.

Multivariate analysis identified pathologic tumor size and nodal status as independent prognostic factors for DFS.

Researchers used these criteria to categorize patients as low risk (pathologic tumor size 2 cm or less and N0 disease), intermediate risk (pathologic tumor size 2 cm or less and any N category, or pathologic tumor size greater than 2 cm and N0-3), or high risk (pathologic tumor size greater than 2 cm and N4+).

Women in the low- or intermediate-risk groups (89% of the study cohort) achieved comparable 5-year DFS with a 9-week trastuzumab course as a 1-year course (88% vs. 89%; HR = 1.02; 95% CI, 0.78-1.33). However, the risk for cardiac events was almost three times lower (4.5% vs. 12.8%; RR = 2.88; 95% CI, 1.85-4.47).

Noninferiority cannot be claimed based on these results because the study was underpowered due to difficulty recruiting, according to Pierfranco Conte, MD, professor of oncology at University of Padua and director of the division of medical oncology at Instituto Oncologico Vento in Italy.

“Based on our data, 1 year trastuzumab remains the standard treatment for women with HER2-positive early breast cancer,” Conte said in a press release. “[However], physicians can stop trastuzumab before 1 year [for] patients who develop a cardiac event during treatment without compromising efficacy and can consider shorter-duration trastuzumab treatment [for] patients at risk [for] cardiac toxicity and at low or intermediate risk [for] breast cancer relapse.”

The shorter trastuzumab course also may be considered for patients who cannot afford longer treatment, Conte said.

The results demonstrate that patients with a high tumor load definitely derive substantial benefit from a longer course of trastuzumab, according to Nadia Harbeck, MD, PhD, head of the breast center at University of Munich.

“The results may impact on clinical decision-making, although it is an exploratory analysis of a negative trial so does not meet the criteria to be practice-changing,” Harbeck, who was not involved in the study, said in the press release. “I think it will influence clinicians and patients in that if patients cannot complete 1 year of trastuzumab, those patients with low tumor burden can feel reassured that they have not lost out on efficacy.” – by Mark Leiser

Reference: Conte PF, et al. Abstract 191PD_PR. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.

Disclosure: Conte reports institutional research funding from Roche, as well as a speakers’ bureau role with Roche/Genentech. Please see the abstract for all other authors’ relevant financial disclosures.