Shorter Treatment Option Studied for HER2 Early Breast Cancer

Women with HER2-positive early breast cancer with small tumors have similar disease-free survival (DFS) and lower risk of cardiac toxicity with a 9-week course of adjuvant trastuzumab compared with those treated for 1 year.¹ A second study showed that a 6-month course of adjuvant trastuzumab was cost-effective compared to 12 months.²

Current guidelines recommend 1 year of anti-HER2 antibody therapy as part of standard adjuvant treatment for HER2-positive early breast cancer patients, but there is interest in knowing if similar efficacy can be achieved with fewer risk of side effects lower costs.

The results were presented at the ESMO 2018 Annual Congress, held October 19-23 in Munich, Germany.

The Short-HER trial randomized 1254 HER2-positive early breast cancer patients to either 9 weeks or 1 year of treatment with trastuzumab. Both groups also received chemotherapy. Results after a median of 6 years' follow-up showed the short course did not achieve noninferiority but was associated with a reduction in the rate of severe cardiac toxicity

Multivariate analysis showed that pathologic tumour size (pT) and nodal status (N) were independent prognostic factors for DFS. Researchers identified 3 prognostic groups:

• Low risk (pT < 2cm and N0), accounting for 37.5% of patients
• Intermediate risk (pT < 2cm and any N category), accounting for 51.9%
• High risk (pT > 2cm and N4+), accounting for 10.5% of patients

Results showed that patients with low and intermediate risk had similar 5-year DFS with a 9-week course of trastuzumab (88%) as with 1-year course (89%; hazard ratio 1.02, 95% confidence interval [CI] 0.78-1.33), but their risk of cardiac events was nearly 3 times lower (4.5% vs 12.8%, relative risk 2.88; 95% CI 1.85-4.47). Women at low and intermediate risk of relapse accounted for 89% of patients in the study.

In the second study, treatment for 6 months gave an average cost saving of £9793.25 or approximately $12,796.84 (95% CI £9515.86-£10,071.64 [$12,434.37-$13,160.61]) per patient. Trastuzumab treatment and administration accounted for the vast majority of this cost saving, with the rest coming from cardiac assessment and treatment costs and inpatient days. There was also no evidence of detriment to quality of life.

Researchers analyzed the cost-effectiveness of a 6-month course of adjuvant trastuzumab compared with the standard 12-month course in patients with HER2-positive early breast cancer taking part in the PERSEPHONE trial. This is the largest phase 3 randomized trial to compare 6 months with 12 months of trastuzumab and demonstrated noninferiority of reduced-duration trastuzumab.

The average quality-adjusted life years (QALYs) for an individual in the 6-month arm and 12-month arm were 1.146 (95% CI: 1.131-1.161) and 1.128 (95% CI: 1.113-1.144), respectively, giving an average QALY difference of 0.018 (95% CI: - 0.003-0.039). The 6-month treatment arm dominated, with a probability of being cost-effective of 100%.

References

1. Conte P. 9 weeks versus 1 year adjuvant trastuzumab for HER2+ early breast cancer: subgroup analysis of the ShortHER trial allows to identify patients for whom a shorter trastuzumab administration may have a favourable risk/benefit ratio. Presented at: ESMO 2018 Congress; October 20, 2018; Abstract 191PD_PR.

2. Hulme C. PERSEPHONE: 6 versus 12 months (M) of adjuvant trastuzumab in patients (PTS) with HER2 positive early breast cancer (EBC): cost effectiveness analysis results. Presented at: ESMO 2018 Congress; October 20, 2018; Abstract LBA12_PR.