In the Japanese RESPECT trial reported in the Journal of Clinical Oncology, Sawaki et al found that noninferiority of adjuvant trastuzumab alone vs with chemotherapy was not shown for disease-free survival among women with HER2-positive breast cancer between the ages of 70 and 80 years. However, a small difference in restricted mean survival time was observed, and health-related quality of life was better with trastuzumab monotherapy.

Study Details

In the multicenter open-label noninferiority trial, 266 patients (intent-to-treat population) were randomly assigned between October 2009 and November 2014 to receive trastuzumab alone at a loading dose of 8 mg/kg and a maintenance dose of 6 mg/kg every 3 weeks for 1 year (n = 135), or trastuzumab plus investigator’s choice of seven chemotherapy regimens (n = 131). The primary endpoint was disease-free survival. Noninferiority of trastuzumab monotherapy was to be demonstrated if the upper limit of the 95% confidence interval (CI) of the hazard ratio (HR) did not exceed 1.69.

Disease-Free Survival and Other Outcomes

Patients were followed for a mean of 4.1 years (range = 0.3–8.0 years). Three-year disease-free survival was 89.5% with trastuzumab monotherapy vs 93.8% with trastuzumab plus chemotherapy (HR = 1.36, 95% CI = 0.72–2.58; P = .51), with the noninferiority criterion not being met. The difference in restricted mean survival time for disease-free survival at 3 years was −0.39 months (95% CI = −1.71 to 0.93; P = .56).

Relapse-free survival at 3 years was 92.4% vs 95.3% (HR = 1.33, 95% CI = 0.63–2.79). The difference in restricted mean survival time for relapse-free survival at 3 years was −0.41 months (95% CI = −1.51 to 0.68; P = .53). Overall survival at 3 years was 97.2% vs 96.6% (HR = 1.07, 95% CI = 0.36–3.19).

Adverse Events

Adverse events of any grade that significantly differed in incidence between the trastuzumab monotherapy group and the trastuzumab plus chemotherapy group included neutropenia (9.6% vs 42.0%; P < .0001), anorexia (7.4% vs 44.3%; P < .0001), and alopecia (2.2% vs 71.7%; P <.0001). Grade 4 hematologic adverse events were reported in 0% vs 13.7% of patients (P < .0001). Grade 3 or 4 nonhematologic adverse events occurred in 11.9% vs 29.8% (P = .0003).

Health-Related Quality of Life

Clinically meaningful health-related quality-of-life deterioration—based on a 5-point or greater change from baseline in Functional Assessment of Cancer Therapy–General total score—was observed in 31% of the trastuzumab monotherapy group vs 48% of the trastuzumab plus chemotherapy group (P = .016) at 2 months, and in 19% vs 38% (P = .009) at 1 year.

The investigators concluded, “The primary objective of noninferiority for trastuzumab monotherapy was not met. However, the observed loss of survival without chemotherapy was > 1 month at 3 years. Therefore, and in light of the lower toxicity and more favorable health-related quality-of-life profile, trastuzumab monotherapy can be considered an adjuvant therapy option for selected older patients.”

Masataka Sawaki, MD, PhD, of the Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by the Comprehensive Support Project for Oncology Research of the Public Health Research Foundation, Japan. For full disclosures of the study authors, visit ascopubs.org.