Background: Encorafenib and cetuximab (EC) is the standard of care for pre-treated patients (pts) with BRAF V600E mut mCRC. DpR and ETS previously showed a strong correlation with survival outcomes in mCRC pts receiving 1^st-line therapy. We assessed these tumour dynamic response parameters and their association with clinical outcome in pts with BRAF V600E mut mCRC treated with TT in second-line. Methods: Patients treated in a real-life setting with EC or EC plus binimetinib (ECB) in 20 Italian centres were included. Pts with measurable disease and at least one available disease reassessment by CT scan were eligible. Pts experiencing disease progression as best response (i.e. primary resistant) were not evaluable for DpR and ETS. Associations between DpR and ETS and progression free survival (PFS) and overall survival (OS) were tested by univariate and multivariate models. Results: 105 pts were included: 89 (85%) and 16 (15%) pts were treated with EC and ECB, respectively. Median PFS and OS were 5.2 and 10.3 mos, respectively. Twenty-nine pts (28%) were primary resistant, while 76 (72%) pts achieved disease control (51 [48%] and 25 [24%] pts had SD or CR/PR, respectively). Among baseline characteristics, the presence of peritoneal metastases was a predictor of primary resistance (p = 0.04). Among pts evaluable for response parameters (n = 76), median DpR was 15% and ETS occurred in 28 pts (37%). Mucinous histology was associated with a significantly lower magnitude of DpR (p = 0.005) and a lower rate of ETS (p = 0.002). A significant association between DpR and PFS was observed, both as a dichotomous (ie, ≥ or < median value) and continuous variable in univariate and multivariate analyses. Also RECIST response correlated with PFS in the two models (table). DpR was associated with OS in the univariate analyses, but this was not confirmed in the multivariate models (table). No correlation between ETS and survival, either as a dichotomous (ie, ≥ or < 20%) or a continuous variable, was observed. Conclusions: Having a DpR of at least 15% predicts longer PFS and OS in patients with BRAF V600E mut mCRC receiving TT as second-line treatment. An independent cohort of pts treated with second-line chemotherapy +/- antiangiogenic is under investigation as control group.

*for 10% increase.