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New Approach to Predicting Response to Pertuzumab and Trastuzumab in Breast Cancer

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Key Points

  • Day 15 SULmax on FDG PET-CT was associated with likelihood of pathologic complete response with adjuvant pertuzumab and trastuzumab.
  • Median reduction in SULmax by day 15 was 63.8% in those with pathologic complete response vs 33.5% in those without.

In the phase II TBCRC026 study reported in the Journal of Clinical Oncology, Connolly et al found that early changes in tumor maximum standardized uptake values corrected for lean body mass (SULmax) on [18F]fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were predictive of pathologic complete response to four cycles of neoadjuvant pertuzumab and trastuzumab in estrogen receptor–negative, HER2-positive breast cancer.

The study included 83 evaluable patients from 9 U.S. sites enrolled between January 2014 and August 2017. Patients with stage II/III, estrogen receptor–negative, HER2-positive breast cancer received four cycles of pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) every 3 weeks. FDG PET/CT was performed at baseline and 15 days after treatment initiation.

Association Between SULmax and Response

Pathologic complete response was achieved in 34% of patients. Baseline SULmax was not significantly associated with pathologic complete response. The receiving operator characteristic area under the curve for day 15 SULmax distinguishing patients with vs without pathologic complete response was 0.76 (P = .03).

Compared with patients who achieved pathologic complete response vs those who did not, there was:

  • A significant difference in median reduction in SULmax by day 15 (63.8% vs 33.5%, P < .001)
  • A more commonly observed SULmax reduction of ≥ 40% (86% vs 46%, P < .001; negative predictive value = 88%, positive predictive value = 49%)
  • A significant difference in median day 15 SULmax (1.6 vs 3.9, P < .001)
  • A higher proportion of patients with day 15 SULmax ≤ 3 (93% vs 38%, P < .001; negative predictive value = 94%, positive predictive value = 55%).

The investigators concluded, “Early changes in SULmax predict response to four cycles of [pertuzumab and trastuzumab] 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.”

Roisin M. Connolly, MD, of the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Cancer Institute and Genentech. The study authors' full disclosures can be found at jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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