Abstract P3-03-02: Diffusion-weighted MRI for prediction of pathologic complete response in HER2- breast cancer treated with pembrolizumab plus neoadjuvant chemotherapy
Authors: Wen Li, Nu N Le, Natsuko Onishi, David C Newitt, Jessica E Gibbs, Lisa J Wilmes, John Kornak, Savannah C Partridge, Barbara LeStage, Elissa R Price, Bonnie N Joe, Laura J Esserman, Nola M Hylton
Journal: Cancer Research (2022)

Abstract Background: Checkpoint blockade pembrolizumab has demonstrated great potential to improve pathologic outcome for HER2- breast cancer. The apparent diffusion coefficient (ADC) is a non-contrast MRI-derived biomarker that is sensitive to changes in tumor cellularity. Clinical trial ACRIN 6698, a sub-study of I-SPY 2, demonstrated that ADC can predict pathologic complete response (pCR). This study compares the utility of ADC for early prediction of pCR in patients with HER2- breast cancer randomized to pembrolizumab versus standard neoadjuvant chemotherapy (NACT) in I-SPY 2. Methods: A retrospective analysis of imaging and clinical data was performed on a cohort of 249 women diagnosed with high-risk, stage II/III breast cancer. All patients were randomized to the standard NACT (paclitaxel) or pembrolizumab plus paclitaxel for 12 weeks, followed by doxorubicin plus cyclophosphamide. MRI exams performed at pretreatment (T0) and 3 weeks after the treatment started (T1) were analyzed. Tumor ADC was calculated within manually delineated region-of-interests on diffusion-weighted MRI. The percent change of ADC from T0 to T1 was evaluated in the prediction of pCR after NACT. Statistical analysis included Wilcoxon rank sum test and the area under the ROC curve (AUC). A p-value &amp;lt;0.05 was considered statistically significant. Results: A subcohort of 103 patients with analyzable diffusion-weighted MRI exams and known pCR (n=30)/non-pCR (n=73) outcome were included in this analysis. Among 103 patients, 62 had HR+/HER2- and 41 had triple negative breast cancer. Twenty-eight patients (17 HR+/HER2- and 11 triple negative) were randomized to receive pembrolizumab and 75 (45 HR+/HER2- and 30 triple negative) to standard NACT. Tumor ADC increased at 3 weeks in both standard and pembrolizumab cohorts with median ADC change of 11.5% (interquartile range [IQR]: 4.6, 16.2)% and 14.4% (IQR: 0.2, 19.9)%, respectively. In the pembrolizumab cohort, the difference in ADC change between non-pCR and pCR groups was estimated as -9.7% (95% confidence interval [CI]: -22.4, -0.9), with ADC increasing more in the pCR group. The AUC of predicting pCR in the pembrolizumab cohort was estimated as 0.73 (95%CI: 0.52, 0.93), while it was estimated as 0.63 (95% CI: 0.43, 0.83) in the standard NACT cohort. In comparison, the AUCs using functional tumor volume (FTV) to predict pCR were 0.61 (95%CI: 0.39, 0.83) and 0.66 (95% CI: 0.47, 0.85) in the corresponding cohorts (Table 1). The results suggest that ADC had higher association with pCR than FTV in the pembrolizumab cohort and FTV had higher association than ADC in the standard cohort. Conclusions: Tumor ADC, measured using diffusion-weighted MRI, demonstrates potential as a biomarker for assessing early response to immunotherapy in the neoadjuvant setting for high risk HER2- breast cancer. This study is limited by sample size. Future analysis with larger cohorts is warranted. Table 1.Association between MRI variables and pCRN (pCR rate)Difference between non-pCR and pCR groups (95% CI)AUC (95% CI)pDiffusion weighted MRI (percent change of ADC)Pembrolizumab28 (54%)-9.7 (-22.4, -0.9)0.73 (0.52, 0.93)0.041Standard75 (20%)-5.6 (-13.9, 2.1)0.63 (0.43, 0.83)0.13DCE-MRI (percent change of FTV)Pembrolizumab28 (54%)10.6 (-18.3, 43.9)0.61 (0.39, 0.83)0.34Standard74 (20%)25.3 (-0.6, 49)0.66 (0.47, 0.85)0.056 Citation Format: Wen Li, Nu N Le, Natsuko Onishi, David C Newitt, Jessica E Gibbs, Lisa J Wilmes, John Kornak, Savannah C Partridge, Barbara LeStage, Elissa R Price, Bonnie N Joe, I-SPY 2 TRIAL Imaging Working Group, I-SPY 2 TRIAL Consortium, Laura J Esserman, Nola M Hylton. Diffusion-weighted MRI for prediction of pathologic complete response in HER2- breast cancer treated with pembrolizumab plus neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-03-02.