Early on-treatment (on-Rx) tumor volume reduction (TVR) to predict response to the KEYNOTE-522 (KN-522) regimen in early stage triple negative breast cancer (TNBC).

592 Background: Monitoring clinical response by breast ultrasound (US) during neoadjuvant therapy is considered standard of care. We previously demonstrated that suboptimal on-Rx TVR after neoadjuvant doxorubicin and cyclophosphamide (AC) predicts non-pCR after sequential taxane-based chemo. However, it is unknown if on-Rx TVR has the similar predictive value in pts receiving the KN-522 chemo-immunotherapy regimen. Methods: Pts with early stage TNBC planned to receive the KN-522 regimen were enrolled on the prospective ARTEMIS trial (NCT02276443). Breast US was performed at baseline and after 6 weeks of paclitaxel + carboplatin + pembrolizumab. TVR was defined as the percent reduction of tumor volumes calculated using 3 perpendicular measurements of the index breast lesion. Pathological complete response (pCR) was defined as ypT0/isN0. Logistic regression was used to examine associations between covariates and pCR. Receiver operating characteristic (ROC) analyses were utilized to assess the predictive value of TVR and determine an optimal TVR threshold. Results: 150 pts were included. Clinicopathological characteristics are described in Table 1. The pCR rate was 63%. In uni- and multi-variable analyses, TVR was the only covariate to demonstrate statistically significant association with pCR (aOR:1.9 per 10% TVR, p&lt;0.001). In ROC analyses, the area under the ROC curve (AUC-ROC) was 0.74 (95% CI: 0.66-0.82). TVR&gt;50%, selected based on the Youden index, predicted pCR with the following performance characteristics: positive predictive value: 73%; negative predictive value: 79%; sensitivity: 94%; specificity: 41%. Conclusions: Early on-Rx TVR by breast US outperforms clinicopathological covariates in the prediction of pCR in pts with TNBC receiving the KN-522 regimen and should be leveraged for risk stratification and design of response-adapted neoadjuvant clinical trials for pts with TNBC. Clinical trial information: NCT022766443 . pCR (n=95) Non-pCR (n=55) Odds ratio (OR) p value (univariable) Adjusted OR (aOR) p value (multivariable) Median 6w TVR – % (interquartile range [IQR]) 84 (72-90) 69 (38-83) 1.5 &lt;0.001 1.9 &lt;0.001 Median age – years (IQR) 51 (40-61) 51 (43-64) 0.98 0.25 1.0 0.73 N (%) Ethnicity White 50 (53) 33 (60) 1 1 Black 15 (6) 10 (18) 1.1 0.84 0.9 0.91 Hispanic/Latino 25 (26) 6 (11) 2.4 0.08 1.9 0.32 Asian 5 (5) 6 (11) 0.6 0.36 0.2 0.12 T stage T1/2 79 (83) 46 (84) 1 1 T3/4 16 (17) 9 (16) 1.0 0.94 1.2 0.77 Nodal status <jats:td