Early Changes in SULmax Could Predict Pathological CR to Pertuzumab/Trastuzumab in HER2+ Breast Cancer

Investigators identified that early changes in standardized uptake value corrected for lean body mass may be able to predict pathologic complete response to pertuzumab AND trastuzumab in patients with HER2-positive breast cancer.

Early changes in the standardized uptake value corrected for lean body mass (SULmax) could be predictive of pathologic complete response (pCR) to pertuzumab (Perjeta) and trastuzumab (Herceptin) for patients with estrogen receptor–negative, HER2-positive breast cancer, according to findings from the phase 2 TBCRC026 study (NCT01937117) published in the Journal of Clinical Oncology.

Findings from the study identified a significant difference in median percent reduction in SULmax by C1D15 among patients who achieved pCR (63.8%) and those who didn’t (41.8%; P=.004). Investigators also identified an estimated odds ratio (OR) of 1.03 that was associated with a 1% reduction of SULmax (95% CI, 1.01-1.06).

The ROC analysis, which utilized percent reduction in SULmax as the predictor, yielded an area under the curve of 0.72 (80% CI, 0.64-0.80; P = .12); this did not reject the null hypothesis for the primary end point. The exploratory cutoff of40% or more vs less than 40% reduction in SULmax demonstrated a sensitivity of 83% and a specificity of 48% for identifying patients who achieved a pCR.

“In the TBCRC026 trial, we investigated whether early changes in SULmax on FDG-PET-CT can predict pCR after HER2-directed therapy with pertuzumab and trastuzumab alone (no chemotherapy) in ER-negative, HER2-positive early-stage breast cancer,” the investigators of the study said.

Investigators theorized that early measurement of SULmax through the use of 18F-labeled fluorodeoxyglucose (FDG) PET-CT may help predict potential pCR to pertuzumab and trastuzumab. All patients who enrolled on the study underwent baseline C1D15 and FDG-PET-CT.

The study enrolled 88 women at 9 different sites from January 2014 to August 2017. Only 83 were evaluable for the primary analysis, all of whom underwent primary surgery. In total, 85% of patients (n = 77/88) completed all 4 cycles of pertuzumab and trastuzumab. Additionally, 25 (28%) patients received neoadjuvant non-study therapy and did not obtain pCR. Additionally, 22 of these 25 patients had histologically confirmed residual disease after 12 weeks of pertuzumab and trastuzumab.

Other non-study neoadjuvant therapies included taxane and carboplatin–based therapy (n = 17) and taxane-based therapy with pertuzumab and trastuzumab (n = 7). One patient received a fifth cycle of pertuzumab and trastuzumab and 2 received anthracycline based neoadjuvant chemotherapy.

In total, pCR was achieved in 18 (22%) of patients after 4 cycles of pertuzumab and trastuzumab alone (95% CI, 13-22). Investigators assumed that the patients who withdrew consent did not obtain pCR, and they created an estimated of 18 (20%) of patients for pCR (95% CI, 13-32). Among patients who had confirmed residual disease or clinical progression after 12 weeks of the experimental regimen and achieved an additional neoadjuvant non-study treatment, 7 of 22 (32%) had pCR at the time of surgery. Additionally, 7 (8%) patients experienced clinical progression on pertuzumab and trastuzumab after 2 to 4 cycles of treatment.

Investigators also identified a difference among the evaluable patients who experienced a change in median C1D15 SULmax and achieved a pCR and those who did not (1.6 vs 3.6; P< .001). Additional findings from the ROC analysis identified an AUC of 0.77 (80% CI, 0.70-0.83; P = .009). The cutoff of 3 or less vs over 3 yielded in C1D15 SULmax yielded a high negative predictive value for pCR over other cut points. A significantly higher proportion of C1D15 SULmax of 3 or less was noted in patients who obtained pCR compared with those who did not (100% vs 45%; P< .001).

Although the study did not meet its primary end point, early change in SULMax appeared to be predictive of the combination in this patient population. After undergoing optimization, this imaging strategy could be used to help better select patients for treatment with pertuzumab/trastuzumab.


Connolly RM, Leal JP, Solnes L, et al. Updated results of TBCRC026: phase II trial correlating standardized uptake value with pathological complete response to pertuzumab AND trastuzumab in breast cancer. J Clin Oncol. 2021;39(20):2247-2256. doi:10.1200/JCO.21.00280