TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer

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.

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Updated Results of TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathological Complete Response to Pertuzumab and Trastuzumab in Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.21.00280 ◽

2021 ◽

pp. JCO.21.00280

Author(s):

Roisin M. Connolly ◽

Jeffrey P. Leal ◽

Lilja Solnes ◽

Chiung-Yu Huang ◽

Ashley Carpenter ◽

...

Keyword(s):

Breast Cancer ◽

Area Under The Curve ◽

Standardized Uptake Value ◽

Complete Response ◽

Her2 Positive ◽

Percent Change ◽

Her2 Positive Breast Cancer ◽

Positron Emission ◽

Estrogen Receptor Negative ◽

Positive Breast Cancer

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.

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Neoadjuvant Pertuzumab plus Trastuzumab in Combination with Docetaxel and Carboplatin in Patients with HER2 Positive Breast Cancer: Real-World Data from a National Institute of Oncology in Poland.

10.20944/preprints202201.0164.v1 ◽

2022 ◽

Author(s):

Agnieszka Irena Jagiełło-Gruszfeld ◽

Magdalena Rosinska ◽

Malgorzata Meluch ◽

Katarzyna Pogoda ◽

Anna Niwińska ◽

...

Keyword(s):

Breast Cancer ◽

Pathologic Complete Response ◽

Complete Response ◽

Her2 Positive ◽

Real World Data ◽

Cancer Subtypes ◽

Cancer Management ◽

Her2 Positive Breast Cancer ◽

Neoadjuvant Systemic Therapy ◽

Positive Breast Cancer

Neoadjuvant systemic therapy has now become the the standard in early breast cancer management. Chemotherapy in combination with trastuzumab +/- pertuzumab targeted therapy can improve rates of pathologic complete response (pCR) in patients with HER2-positive breast cancer. Achieving a pCR is considered a good prognostic factor, in particular in patients with more aggressive breast cancer subtypes such as TNBC or HER2 positive cancers. Furthermore, most studies demonstrate that chemotherapy in combination with trastuzumab and pertuzumab is well tolerated. The retrospective analysis presented here concentrates on neoadjuvant therapy with the TCbH-P regimen, with a particular emphasis on patients over 60 years of age. We analysed the factors affecting the achievement of pCR and presented adverse effects of the applied therapies, which opened a discussion about optimizing the therapy of older patients with HER-2 positive breast cancer.

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