Updated Results of TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathological 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 value corrected for lean body mass (SULmax) on ¹⁸F-labeled fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) would predict pathologic complete response (pCR) to pertuzumab and trastuzumab (PT).

Patients and methods: Patients with stage II or III, estrogen receptor-negative, HER2-positive breast cancer received four cycles of neoadjuvant PT. ¹⁸F-labeled 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 percent change in SULmax by C1D15 predicting pCR is ≤ 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 22%. Receiver operator characteristic analysis of percent change in SULmax by C1D15 yielded an area under the curve of 0.72 (80% CI, 0.64 to 0.80; one-sided P = .12), which did not reject the null hypothesis. However, between patients who obtained pCR and who did not, a significant difference in median percent reduction in SULmax by C1D15 was observed (63.8% v 41.8%; P = .004) and SULmax reduction ≥ 40% was more prevalent (83% v 52%; P = .03; positive predictive value, 31%). Participants not obtaining a 40% reduction in SULmax by C1D15 were unlikely to obtain pCR (negative predictive value, 91%).

Conclusion: Although the primary objective was not met, early changes in SULmax predict response to PT in estrogen receptor-negative and HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate tailoring of therapy in this setting.

FIG 1.

Study flow diagram. Study treatment = PT. ^aAll patients remained evaluable. ^bReasons for withdrawal of consent include one participant refused further participation after C1D1, one participant refused further participation after C2D1, one patient refused further participation after study treatment was completed, and one patient withdrew consent because of unacceptable toxicity. PT, pertuzumab and trastuzumab.

FIG 2.

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

FIG 3.

Box plots of (A) 15 days after PT initiation (C1D15), and (B) percent reduction in SULmax in patients with pCR versus no pCR. The horizontal line inside the box shows the median. The lower and upper hinges of the box represent the 25th and 75th percentiles, respectively. The circles represent actual values of D15 and percent reduction in SULmax. pCR, pathologic complete response; PT, pertuzumab and trastuzumab; SULmax, maximum standardized uptake value corrected for lean body mass.

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-FDG PET images (baseline and D15) in patients (A and B) with and (C and D) without pCR. ¹⁸F-FDG, ¹⁸F-labeled fluorodeoxyglucose; pCR, pathologic complete response; PET, positron emission tomography.