Abstract P6-17-19: What to do with trastuzumab therapy after achieving radiological complete remission (rCR) in HER2+ metastatic breast cancer (MBC)?
Authors: Steenbruggen TG , Bouwer NI , Smorenburg CH , Rier HN , Jager A , Beelen KJ , ten Tije AJ , de Jong PC , Drooger JC , Holterhues C , Horlings HM , Sanders J , Levin M-D , Sonke GS 
Published: May 2019

Abstract
Intro MBC is generally considered incurable, but patients with HER2+ disease treated with trastuzumab do relatively well and some have an exceptional durable response and survive over 10 years. We analyzed the clinical-pathological characteristics associated with long-term survival in patients with HER2+ MBC treated with trastuzumab. In addition, we studied the effect of stopping trastuzumab in case of rCR.
Methods We included all patients with HER2+ MBC treated with first- or second-line trastuzumab-based palliative therapy between January 2000 and December 2014 in 8 Dutch hospitals (Netherlands Cancer Institute, Erasmus Medical Center, Albert Schweitzer Hospital, Reinier de Graaf Hospital, Amphia Hospital, St. Antonius Hospital, Ikazia Hospital, Haga Hospital). Patients were identified through the Netherlands Cancer Registry and linkage with the institutes' tumor registries. Data was collected from medical records using case record forms. Primary endpoint was overall survival (OS), defined as first-date of MBC until death due to any cause. Kaplan-Meier survival estimates were calculated and multivariable Cox-regression models used to identify prognostic factors for improved survival. Time to progression (TTP) after achieving rCR for patients who continued and stopped trastuzumab and breast cancer specific survival were secondary outcomes.
Results We included 744 patients (median age 53, range 24-87). Median follow-up (FU) was 109 months (range 0-178). Clinical factors associated with improved survival in multivariable analyses were single-organ metastases, ER-positivity, no skin or liver metastases, no prior trastuzumab, local therapy of metastatic disease and achievement of rCR. In line with our first single center analyses1, achievement of rCR was the strongest predictor of improved survival (multivariable HR 0.30, 95%CI 0.20-0.46). RCR was observed in 71 patients (10%), of whom 60 had been treated with trastuzumab and chemotherapy, 9 with trastuzumab and hormonal therapy, and 2 with hormonal therapy. In patients with rCR the estimated 10-year OS was 53% versus 7% in patients who did not achieve rCR (p&lt;0.001).
Thirty patients stopped trastuzumab after achieving rCR. Median time between onset of rCR and last gift of trastuzumab in these patients was 6 months (0-132). Twenty-one patients (70%) remain in complete remission after a median FU of 75 months (range 54-90) since onset of rCR. Nine patients experienced disease progression after a median time of 14 months (range 9-62) since last gift of trastuzumab. Of these, 8 patients died due to MBC and one again achieved an ongoing rCR. Out of 39 patients who continued trastuzumab after achieving rCR, 12 are in ongoing remission after a median FU of 71 months (range 51-91). In this group median TTP was 14 months (range 5-23).
Conclusion Achieving rCR is strongly associated with long-term survival in patients with HER2+ MBC. Seventy percent of patients who stopped trastuzumab after achieving rCR remained in remission, suggesting this can be an attractive approach in selected patients. External validation of these findings is required, however, as well as additional analyses to characterize the patients -and their tumors- who achieved rCR.
1 Steenbruggen, CancerRes 2017
Citation Format: Steenbruggen TG, Bouwer NI, Smorenburg CH, Rier HN, Jager A, Beelen KJ, ten Tije AJ, de Jong PC, Drooger JC, Holterhues C, Horlings HM, Sanders J, Levin M-D, Sonke GS. What to do with trastuzumab therapy after achieving radiological complete remission (rCR) in HER2+ metastatic breast cancer (MBC)? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-19.