As reported in the Journal of Clinical Oncology by Roisin M. Connolly, MD, and colleagues, updated results of the phase II TBCRC026 trial indicate an association of early F-18 fluorodeoxyglucose positron-emission tomography/computed tomography (F-18 FDG PET/CT) maximum standardized uptake value (SULmax) with the likelihood of pathologic complete response to neoadjuvant pertuzumab/trastuzumab in patients with HER2-positive breast cancer.
Study Details
In the U.S. multicenter study, 88 women (83 evaluable) with stage II and III estrogen receptor–negative, HER2-positive breast cancer were enrolled between January 2014 and August 2017. Patients received 12 weeks of neoadjuvant treatment consisting of pertuzumab every 3 weeks at a loading dose of 840 mg followed by 420 mg, and trastuzumab every 3 weeks at a loading dose of 8 mg/kg followed by 6 mg/kg.
F-18 FDG PET/CT was performed at baseline and at day 15 after start of pertuzumab/trastuzumab, with SULmax corrected for lean body mass. A total of 80 evaluable patients was required to test the null hypothesis that the receiver operating characteristic area under the curve (AUC) of percent change in tumor SULmax by day 15 predicting pathologic complete response would be ≤ 0.65, with a one-sided type I error rate of 10%.
Although the primary objective was not met, early changes in SULmax predict response to pertuzumab/trastuzumab in estrogen receptor–negative and HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate tailoring of therapy in this setting.— Roisin M. Connolly, MD, and colleagues
Tweet this quote
Key Findings
A total of 25 patients (28%) received nonstudy neoadjuvant therapy and were classified as not achieving pathologic complete response in the intention-to-treat analysis; 22 had histologically confirmed residual disease after 12 weeks of pertuzumab/trastuzumab and/or clinical progression on study therapy.
Pathologic complete response was achieved in 18 (22%, 95% confidence interval [CI] = 13%–32%) of 83 patients after four cycles of pertuzumab/trastuzumab alone. Analysis of percent change in SULmax by day 15 showed an AUC of 0.72 (80% CI = 0.64–0.80, P = .12), which did not reject the null hypothesis.
A significant difference in median percent reduction in SULmax by day 15 was observed between patients who achieved vs did not achieve pathologic complete response (63.8% vs 41.8%, P = .004), with an estimated odds ratio of 1.03 (95% CI = 1.01–1.06) for each 1% reduction in SULmax.
SULmax reduction of ≥ 40% was more common among patients with vs without pathologic complete response (83% vs 52%, P = .03). A cutoff of ≥ 40% vs < 40% reduction in SULmax was associated with a sensitivity of 83%, specificity of 48%, and positive predictive value of 31% for achievement of pathologic complete response. A reduction of < 40% was associated with a negative predictive value of 91%.
The investigators concluded, “Although the primary objective was not met, early changes in SULmax predict response to pertuzumab/trastuzumab in estrogen receptor–negative and HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate tailoring of therapy in this setting.”
Dr. Connolly is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Translational Breast Cancer Research Consortium (TBCRC) and its foundation partners (The AVON Foundation, The Breast Cancer Research Foundation, and Susan G. Komen for the Cure), National Cancer Institute grants, Genentech Inc, and others. For full disclosures of the study authors, visit ascopubs.org.
