Trastuzumab versus observation for HER2 non amplified early breast cancer with Circulating Tumor Cells (EORTC 90091-10093, BIG 1-12, Treat CTC): A randomized phase 2 trial

Abstract

Background

Trastuzumab improves the outcome of women with HER2 positive breast cancer. We aimed to assess whether trastuzumab decreases the detection rate of Circulating Tumor Cells (CTCs) in women with high risk, HER2 non-amplified, early breast cancer.Patients and Methods: The EORTC 90091-10093 BIG 1-12 Treat CTC is a phase 2 trial, conducted in 70 hospitals and 6 CTC laboratories across 5 European countries. Patients with centrally confirmed HER2 non-amplified breast cancer and ≥1 centrally confirmed CTC per 15mL of blood by CellSearch® following surgery and (neo)adjuvant chemotherapy were randomized (1:1) to 6 cycles of trastuzumab intravenously versus 18 weeks of observation. Randomization was stratified for center, locally confirmed estrogen receptor (ER) status and adjuvant versus neoadjuvant chemotherapy. The primary endpoint was rate of detection of ≥ 1 CTC per 15mL of blood at week 18. Secondary endpoints were invasive disease-free survival (iDFS) and cardiac safety.

Results

Between 30 April 2013 and 17 October 2016, 1317 patients were screened; 95 (7.2%) had detectable CTC(s), and 63 (4.8%) were randomized to trastuzumab (n = 31) or observation (n = 32). Fifty-eight patients were evaluable for the primary endpoint, 29 in each arm. In 9 of the 58 patients, CTC(s) were still detected at week 18: 5 in the trastuzumab and 4 in the observation arm (one-sided Fisher exact test, p = 0.765). An Independent Data Monitoring Committee recommended stopping further accrual for futility for the primary endpoint. Median follow-up at database lock was 13 months (IQR 4-16.5). The 1-year iDFS was 93.8% (95% CI 77.3-98.4) in the observation versus 84.8% (95% CI 63.4-94.2) in the trastuzumab arm. No grade 2-4 cardiac events were observed in the trastuzumab arm.

Conclusion

Trastuzumab does not decrease the detection rate of CTCs in HER2 non-amplified, non-metastatic breast cancer.