T G Steenbruggen1, N I Bouwer2, C H Smorenburg1, H N Rier2, A Jager3, K Beelen4, A J Ten Tije5, P C de Jong6, J C Drooger7, C Holterhues8, J J E M Kitzen2, M -D Levin2, G S Sonke9. 1. Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. 2. Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands. 3. Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. 4. Department of Internal Medicine, Reinier de Graaf Hospital, Delft, The Netherlands. 5. Department of Internal Medicine, Amphia Hospital, Breda, The Netherlands. 6. Department of Medical Oncology, Sint Antonius Hospital, Utrecht, Utrecht, The Netherlands. 7. Department of Medical Oncology, Ikazia Hospital, Rotterdam, The Netherlands. 8. Department of Internal Medicine, Haga Hospital, The Hague, The Netherlands. 9. Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. g.sonke@nki.nl.
Abstract
PURPOSE: Patients with HER2-positive metastatic breast cancer (MBC) treated with trastuzumab may experience durable tumor response for many years. It is unknown if patients with durable radiological complete remission (rCR) can discontinue trastuzumab. We analyzed clinical characteristics associated with rCR and overall survival (OS) in a historic cohort of patients with HER2-positive MBC and studied the effect of stopping trastuzumab in case of rCR. METHODS: We included patients with HER2-positive MBC treated with first or second-line trastuzumab-based therapy in eight Dutch hospitals between 2000 and 2014. Data were collected from medical records. We used multivariable regression models to identify independent prognostic factors for rCR and OS. Time-to-progression after achieving rCR for patients who continued and stopped trastuzumab, and breast cancer-specific survival were also evaluated. RESULTS: We identified 717 patients with a median age of 53 years at MBC diagnosis. The median follow-up was 109 months (IQR 72-148). The strongest factor associated with OS was achievement of rCR, adjusted hazard ratio 0.27 (95% CI 0.18-0.40). RCR was observed in 72 patients (10%). The ten-year OS estimate for patients who achieved rCR was 52 versus 7% for patients who did not achieve rCR. Thirty patients with rCR discontinued trastuzumab, of whom 20 (67%) are alive in ongoing remission after 78 months of median follow-up since rCR. Of forty patients (58%) who continued trastuzumab since rCR, 13 (33%) are in ongoing remission after 68 months of median follow-up. Median time-to-progression in the latter group was 14 months. CONCLUSIONS: Achieving rCR is the strongest predictor for improved survival in patients with HER2-positive MBC. Trastuzumab may be discontinued in selected patients with ongoing rCR. Further research is required to identify patients who have achieved rCR and in whom trastuzumab may safely be discontinued.
PURPOSE:Patients with HER2-positive metastatic breast cancer (MBC) treated with trastuzumab may experience durable tumor response for many years. It is unknown if patients with durable radiological complete remission (rCR) can discontinue trastuzumab. We analyzed clinical characteristics associated with rCR and overall survival (OS) in a historic cohort of patients with HER2-positive MBC and studied the effect of stopping trastuzumab in case of rCR. METHODS: We included patients with HER2-positive MBC treated with first or second-line trastuzumab-based therapy in eight Dutch hospitals between 2000 and 2014. Data were collected from medical records. We used multivariable regression models to identify independent prognostic factors for rCR and OS. Time-to-progression after achieving rCR for patients who continued and stopped trastuzumab, and breast cancer-specific survival were also evaluated. RESULTS: We identified 717 patients with a median age of 53 years at MBC diagnosis. The median follow-up was 109 months (IQR 72-148). The strongest factor associated with OS was achievement of rCR, adjusted hazard ratio 0.27 (95% CI 0.18-0.40). RCR was observed in 72 patients (10%). The ten-year OS estimate for patients who achieved rCR was 52 versus 7% for patients who did not achieve rCR. Thirty patients with rCR discontinued trastuzumab, of whom 20 (67%) are alive in ongoing remission after 78 months of median follow-up since rCR. Of forty patients (58%) who continued trastuzumab since rCR, 13 (33%) are in ongoing remission after 68 months of median follow-up. Median time-to-progression in the latter group was 14 months. CONCLUSIONS: Achieving rCR is the strongest predictor for improved survival in patients with HER2-positive MBC. Trastuzumab may be discontinued in selected patients with ongoing rCR. Further research is required to identify patients who have achieved rCR and in whom trastuzumab may safely be discontinued.
Authors: Jennifer Y Sheng; Cesar A Santa-Maria; Neha Mangini; Haval Norman; Rima Couzi; Raquel Nunes; Mary Wilkinson; Kala Visvanathan; Roisin M Connolly; Evanthia T Roussos Torres; John H Fetting; Deborah K Armstrong; Jessica J Tao; Lisa Jacobs; Jean L Wright; Elissa D Thorner; Christine Hodgdon; Samantha Horn; Antonio C Wolff; Vered Stearns; Karen L Smith Journal: JCO Oncol Pract Date: 2020-06-30
Authors: Tessa G Steenbruggen; Michael Schaapveld; Hugo M Horlings; Joyce Sanders; Sander J Hogewoning; Esther H Lips; Marie-Jeanne T Vrancken Peeters; Niels F Kok; Terry Wiersma; Laura Esserman; Laura J van 't Veer; Sabine C Linn; Sabine Siesling; Gabe S Sonke Journal: JNCI Cancer Spectr Date: 2021-02-04
Authors: Nathalie I Bouwer; Tessa G Steenbruggen; Hánah N Rier; Jos J E M Kitzen; Carolien H Smorenburg; Marlies L van Bekkum; Paul C de Jong; Jan C Drooger; Cynthia Holterhues; Marcel J M Kofflard; Eric Boersma; Gabe S Sonke; Mark-David Levin; Agnes Jager Journal: Int J Cancer Date: 2022-04-27 Impact factor: 7.316