Mette S van Ramshorst1, Erik van Werkhoven2, Aafke H Honkoop3, Vincent O Dezentjé4, Irma M Oving5, Ingrid A Mandjes2, Inge Kemper1, Carolien H Smorenburg1, Jacqueline M Stouthard1, Sabine C Linn1, Gabe S Sonke6. 1. Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. 2. Department of Biometrics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. 3. Department of Medical Oncology, Isala, Dokter van Heesweg 2, 8025 AB Zwolle, The Netherlands. 4. Department of Medical Oncology, Reinier de Graaf Gasthuis, Reinier de Graafweg 5, 2625 AD Delft, The Netherlands. 5. Department of Medical Oncology, Ziekenhuisgroep Twente, Zilvermeeuw 1, 7609 PP Almelo, The Netherlands. 6. Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: g.sonke@nki.nl.
Abstract
BACKGROUND: The addition of pertuzumab to neoadjuvant trastuzumab-based chemotherapy improves pathologic complete response rates in HER2-positive breast cancer. However, increased toxicity has been reported with the addition of pertuzumab, and this may differ between various chemotherapy backbone regimens. We evaluated toxicities of pertuzumab when added to either FEC-T (5-fluorouracil, epirubicin, cyclophosphamide, trastuzumab) or weekly paclitaxel, trastuzumab, carboplatin (PTC). METHODS: The TRAIN-2 study is a neoadjuvant randomized controlled trial in stage II and III HER2-positive breast cancer (NCT01996267). Patients are randomly assigned to receive either three cycles of FEC-T plus pertuzumab or three cycles of PTC plus pertuzumab, followed by six cycles of PTC plus pertuzumab in both arms. Toxicities are described per treatment arm according to the Common Toxicity Criteria for Adverse Events version 4.03. RESULTS: This analysis includes 110 patients balanced over both treatment arms. Neutropenia was the most common hematologic toxicity, with grade 3-4 occurring in 53% in the FEC-T-arm and in 51% in the PTC-arm. Febrile neutropenia occurred in 9% in the FEC-T arm and did not occur in the PTC-arm. Secondary G-CSF prophylaxis was used in 35-40% of patients. Asymptomatic ejection fraction decrease grade 2 was observed in 24% in the FEC-T-arm and 11% in the PTC-arm. The most common grade 3-4 non-hematologic toxicity was diarrhea (5% in the FEC-T-arm and 18% in the PTC-arm). CONCLUSIONS: Pertuzumab in combination with FEC-T mostly causes neutropenia, and when added to PTC mostly causes diarrhea. Significant cardiac toxicity is rare with both regimens, and toxicity is overall well manageable.
RCT Entities:
BACKGROUND: The addition of pertuzumab to neoadjuvant trastuzumab-based chemotherapy improves pathologic complete response rates in HER2-positive breast cancer. However, increased toxicity has been reported with the addition of pertuzumab, and this may differ between various chemotherapy backbone regimens. We evaluated toxicities of pertuzumab when added to either FEC-T (5-fluorouracil, epirubicin, cyclophosphamide, trastuzumab) or weekly paclitaxel, trastuzumab, carboplatin (PTC). METHODS: The TRAIN-2 study is a neoadjuvant randomized controlled trial in stage II and III HER2-positive breast cancer (NCT01996267). Patients are randomly assigned to receive either three cycles of FEC-T plus pertuzumab or three cycles of PTC plus pertuzumab, followed by six cycles of PTC plus pertuzumab in both arms. Toxicities are described per treatment arm according to the Common Toxicity Criteria for Adverse Events version 4.03. RESULTS: This analysis includes 110 patients balanced over both treatment arms. Neutropenia was the most common hematologic toxicity, with grade 3-4 occurring in 53% in the FEC-T-arm and in 51% in the PTC-arm. Febrile neutropenia occurred in 9% in the FEC-T arm and did not occur in the PTC-arm. Secondary G-CSF prophylaxis was used in 35-40% of patients. Asymptomatic ejection fraction decrease grade 2 was observed in 24% in the FEC-T-arm and 11% in the PTC-arm. The most common grade 3-4 non-hematologic toxicity was diarrhea (5% in the FEC-T-arm and 18% in the PTC-arm). CONCLUSIONS:Pertuzumab in combination with FEC-T mostly causes neutropenia, and when added to PTC mostly causes diarrhea. Significant cardiac toxicity is rare with both regimens, and toxicity is overall well manageable.
Authors: Charlotte I Stroes; Sandor Schokker; Aafke Creemers; Remco J Molenaar; Maarten C C M Hulshof; Stephanie O van der Woude; Roel J Bennink; Ron A A Mathôt; Kausilia K Krishnadath; Cornelis J A Punt; Rob H A Verhoeven; Martijn G H van Oijen; Geert-Jan Creemers; Grard A P Nieuwenhuijzen; Maurice J C van der Sangen; Laurens V Beerepoot; Joos Heisterkamp; Maartje Los; Marije Slingerland; Annemieke Cats; Geke A P Hospers; Maarten F Bijlsma; Mark I van Berge Henegouwen; Sybren L Meijer; Hanneke W M van Laarhoven Journal: J Clin Oncol Date: 2019-12-06 Impact factor: 44.544
Authors: Thierry Schmidlin; Donna O Debets; Charlotte A G H van Gelder; Kelly E Stecker; Stamatia Rontogianni; Bart L van den Eshof; Kristel Kemper; Esther H Lips; Maartje van den Biggelaar; Daniel S Peeper; Albert J R Heck; Maarten Altelaar Journal: Cell Syst Date: 2019-09-11 Impact factor: 10.304