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.

Trial registration: ClinicalTrials.gov NCT01937117.

FIG 1.

Study flow diagram. Study treatment is pertuzumab and trastuzumab (PT). (*) All patients remained evaluable. (†) Reasons for withdrawal of consent were refusal of further participation after cycle 1, day 1 (n = 1); refusal of further participation after cycle 2, day 1 (n = 1); refusal of further participation after study treatment was completed (n = 1); and withdrawal of consent because of unacceptable toxicity (n = 1).

FIG 2.

Receiver operating characteristic curves for (A) baseline and (B) percentage of change in maximum standardized uptake values corrected for lean body mass (SULmax) and (C) 15 days after pertuzumab and trastuzumab initiation (C1D15). AUC, area under the curve.

FIG 3.

Box plots of 15 days after pertuzumab and trastuzumab initiation (C1D15) and percent reduction in maximum standardized uptake value corrected for lean body mass (SULmax) in patients with pathologic complete response (pCR) v no pCR. The horizontal line inside each box shows the median. The lower and upper hinges of each box represent the 25th and 75th percentiles, respectively. The circles represent actual values of C1D15 and percent reduction in SULmax.

FIG A1.

TBCRC026 study schema. CR, complete response; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; PET, positron emission tomography; PR, progesterone receptor.

FIG A2.

Sample [¹⁸F]fluorodeoxyglucose positron emission tomography images (baseline and day 15) in patients (A and B) with and (C and D) without pathologic complete response.