TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer

Abstract

PURPOSE Predictive biomarkers to identify patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer who may benefit from targeted therapy alone are required. We hypothesized that early measurements of tumor maximum standardized uptake values corrected for lean body mass (SULmax) on [18F]fluorodeoxyglucose positron emission tomography/computed tomography would predict pathologic complete response (pCR) to neoadjuvant pertuzumab and trastuzumab (PT). PATIENTS AND METHODS Patients with stage II/III, estrogen receptor–negative, HER2-positive breast cancer received four cycles of neoadjuvant PT. [18F]Fluorodeoxyglucose positron emission tomography/computed tomography was performed at baseline and 15 days after PT initiation (C1D15). Eighty evaluable patients were required to test the null hypothesis that the area under the curve of percentage of change in SULmax by C1D15 predicting pCR is less than or equal to 0.65, with a one-sided type I error rate of 10%. RESULTS Eighty-eight women were enrolled (83 evaluable), and 85% (75 of 88) completed all four cycles of PT. pCR after PT alone was 34%. Receiver operating characteristic analysis yielded an area under the curve of 0.76 (90% CI, 0.67 to 0.85), which rejected the null hypothesis. Between patients who obtained pCR versus not, a significant difference in median percent reduction in SULmax by C1D15 was observed (63.8% v 33.5%; P < .001), an SULmax reduction greater than or equal to 40% was more prevalent (86% v 46%; P < .001; negative predictive value, 88%; positive predictive value, 49%), and a significant difference in median C1D15 SULmax (1.6 v 3.9; P < .001) and higher proportion of C1D15 SULmax less than or equal to 3 (93% v 38%; P < .001; negative predictive value, 94%; positive predictive value, 55%) were observed. CONCLUSION Early changes in SULmax predict response to four cycles of PT in estrogen receptor–negative, HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate a more tailored approach to therapy in this setting.

Multi-omics analyses identify HSD17B4 methylation-silencing as a predictive and response marker of HER2-positive breast cancer to HER2-directed therapy

“…To predict the response of HER2-positive breast cancer to a HER2-directed agent as well as to chemotherapy, multiple exploratory studies have been conducted. As imaging markers, although digital mammogram, ultrasound, and MRI showed only low negative predictive values 10 , very low tumor residual metabolism measured by 18 F-fluorodeoxyglucose positron emission tomography showed promise as a predictor of pCR 11 – 13 . As molecular markers, PIK3CA mutations were shown to be associated with reduced pCR rates 14 – 16 .…”

A high mitotic score in breast cancer after neoadjuvant chemotherapy is predictive of outcome and associated with a distinct morphology

“…pCR is more common in patients with triple‐negative breast cancer (TNBC) and HER2‐positive cancers than in those with luminal cancers . However, even among these groups, response is variable, with pCR ranging from 15% to 45% for TNBC and from 22% to 63% for HER2‐positive cancers.…”

Utilizing novel fluorothymidine PET imaging in a phase I study of veliparib on an intermittent and continuous schedule given in combination with carboplatin in metastatic breast cancer

“…This is in contrast to a more conventional 5-fluorodeoxyglucose ( 18 FDG) PET scan where uptake of FDG depends on high intake of glucose reflective of increased metabolic rate. There is growing interest in PET-based imaging for early response monitoring in breast cancer 21,22 and uptake of 18 FLT during therapy with PARP inhibitors and DNA damaging agents lends itself well as an attractive imaging modality to study changes in DNA synthesis and early response to this therapy. This multicenter phase I study (NCI8609) sponsored by Cancer Therapy Evaluation Program (CTEP) at the National Cancer Institute (NCI), sought to assess the recommended phase 2 dose (RP2D) of veliparib on an intermittent (7 or 14 day) or continuous (21 day) schedule in combination with every three week schedule of carboplatin in patients with advanced breast cancer that was either triple negative or HR positive (estrogen and/or progesterone receptor positive), HER2 negative with defective FA pathway based on lack of FANCD2 foci in the nuclei of proliferating tumor cells detected by FA Triple Stain Immunofluorescence (FATSI) assay.…”