Long-term outcomes in patients with PET-predicted poor-responsive HER2-positive breast cancer treated with neoadjuvant bevacizumab added to trastuzumab and docetaxel: 5-year follow-up of the randomised Avataxher study

Abstract

Background: The open-label, randomised Phase 2 AVATAXHER study (NCT01142778) demonstrated that early PET assessment identified HER2-positive breast cancer patients who responded poorly to neoadjuvant docetaxel plus trastuzumab. Adding neoadjuvant bevacizumab for PET-predicted poor-responders improved pathological complete response (pCR) rates (43.8% vs 24.0%). We investigated long-term study outcomes. Methods: Patients were treated in three groups. All patients initially received two cycles of standard neoadjuvant therapy with [ 1 ⁸F]-FDG PET conducted before each cycle. Those with 70% change in the maximum standardised uptake value (ΔSUVmax) received four further cycles of standard neoadjuvant therapy (PET responders). PET-predicted poor-responders (ΔSUVmax <70%) were randomised (2:1) to neoadjuvant therapy with (Group A) or without (Group B) bevacizumab for cycles 3À6. All patients received one further cycle of trastuzumab before surgery plus adjuvant trastuzumab (11 cycles). Findings: 142 patients were randomized and treated (PET responders, n = 69; Group A, n = 48; Group B, n = 25). 5-year disease-free survival rates were 90.5% (95% CI: 80.0À95.6%) in PET responders, 90.2% (95% CI: 75.9À96.2%) in Group A, and 76.0% (95% CI: 54.2À88.4%) in Group B. However, no difference was observed between randomised arms in a sensitivity analysis. During adjuvant therapy, the incidence of Grade 3 (Group A: 25.6%; Group B 12.5%) and serious adverse events (Group A: 18.6%; Group B 12.5%) was higher in Group A vs Group B, but with no apparent effect on cardiac events. Interpretation: In patients with HER2-positive breast cancer, an intervention based on early PET assessment and improvement of pCR does not modify disease-free survival.

Joint EANM-SNMMI guideline on the role of 2-[18F]FDG PET/CT in no special type breast cancer

“…Thus, a change in treatment led to an increase in the pCR rate in poor responders. Unfortunately, long-term follow-up of this patient cohort showed that improvement of pCR did not modify disease-free survival [147].…”

Innovations in Positron Emission Tomography and State of the Art in the Evaluation of Breast Cancer Treatment Response

“…Additionally, they noticed that the pCR rate was increased by the addition of bevacizumab to the neoadjuvant scheme (docetaxel plus trastuzumab). However, this increase in the pCR rate did not result in a long-term increase in DFS [ 75 ].…”

Deep radiomics-based fusion model for prediction of bevacizumab treatment response and outcome in patients with colorectal cancer liver metastases: a multicentre cohort study

“… 48 , 49 , 50 In this study, we applied clinical factors to help the DNN understand systemic tumour profiles. We selected SUVmax of PET/CT, 19 , 51 pre-operative CEA, 52 , 53 and primary tumour site 54 , 55 as clinical factors using LASSO regression, which were proven to correlate with bevacizumab efficacy. In fact, combing PET/CT images and clinical factors, the DERBY model achieved an AUC of 0.77 in the external validation cohort, suggesting the validity of these clinical factors.…”