The prospective randomized trial SAKK 22/99 compared first-line trastuzumab plus chemotherapy with the sequential use of trastuzumab followed by chemotherapy plus trastuzumab at progression in patients with stage 4 HER2-positive breast cancer. The main results were recently published in Annals of Oncology. Here we report characteristics and outcomes of patients with long-lasting disease control with trastuzumab alone.
Long-term responders to trastuzumab monotherapy were defined as patients achieving disease control for ≥ 6 months. A risk score was defined as sum of negative prognostic factors (NPFs): ER negative (neg), PgR neg and visceral disease. The HER2:CEP17 FISH ratio was correlated with duration of response. Standard descriptive statistics were used. Survival analysis was done using the Kaplan-Meier method.
Of 175 enrolled pts, 86 were randomised to receive trastuzumab monotherapy until PD. 24 patients (28%) were long-term responders (≥6 months). In a landmark analysis excluding patients who died within 6 months, 5y-overall survival (OS) in long-term responders was 54% (95% CI 31–72) compared to 18% (95% CI 10–30) in short-term responders (log-rank p = 0.02). Baseline characteristics were well-balanced except for visceral disease (see Table, Fisher’s exact test p = 0.01). With each additional NPF the proportion of long-term responders decreased: 0 NPF, 42%; 1 NPF, 40%; 2 NPFs, 35%; 3 NPFs 17%. Median FISH ratio was 4.8 (IQR 4.1–5.3) in long-term responders and 4.7 (IQR 2.5–5.3) in short-term responders; no long-term responders were in the lowest quartile of all FISH ratios.Table:
300P Baseline characteristics
|HER2-long Responders (N = 24)||HER2-short Responders (N = 62)|
|Age (med)||57 years||52 years|
|Visceral disease (yes)||46%||76%|
|FISH (med. Ratio)||4.8||4.7|
|ALP U/l (med)||74||103|
|Hb g/l (med)||130||134|
|WBC G/l (med)||5.8||6.8|
|Endocrine treatment adj (yes)||33%||48%|
Long response to trastuzumab monotherapy is prognostic with significantly higher 5y-survival rates in this cohort. Negative prognostic factors including lower FISH ratio may reduce the chance for long-term response to trastuzumab monotherapy as first line therapy.
Clinical trial identification
Subanalysis of SAKK 22/99 trial; NCT00004935
Legal entity responsible for the study
Swiss Group of Clinical Cancer Research (SAKK)
All authors have declared no conflicts of interest.