Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer.

Autor:	Fernandez-Martinez A; Lineberger Comprehensive Center, University of North Carolina, Chapel Hill, NC.; Department of Genetics, University of North Carolina, Chapel Hill, NC., Krop IE; Department of Medical Oncology, Dana-Farber/Partners CancerCare, Boston, MA., Hillman DW; Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN., Polley MY; Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN., Parker JS; Lineberger Comprehensive Center, University of North Carolina, Chapel Hill, NC.; Department of Genetics, University of North Carolina, Chapel Hill, NC., Huebner L; Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN., Hoadley KA; Lineberger Comprehensive Center, University of North Carolina, Chapel Hill, NC.; Department of Genetics, University of North Carolina, Chapel Hill, NC., Shepherd J; Lineberger Comprehensive Center, University of North Carolina, Chapel Hill, NC.; Department of Genetics, University of North Carolina, Chapel Hill, NC., Tolaney S; Department of Medical Oncology, Dana-Farber/Partners CancerCare, Boston, MA., Henry NL; University of Michigan Rogel Cancer Center, Ann Arbor, MI., Dang C; Memorial Sloan Kettering Cancer Center, New York, NY., Harris L; National Cancer Institute, Cancer Diagnostics Program, Bethesda, MD., Berry D; Division of Biostatistics, MD Anderson Cancer Center, Houston, TX., Hahn O; Alliance Protocol Operations Office, University of Chicago, Chicago, IL., Hudis C; Memorial Sloan Kettering Cancer Center, New York, NY., Winer E; Department of Medical Oncology, Dana-Farber/Partners CancerCare, Boston, MA., Partridge A; Department of Medical Oncology, Dana-Farber/Partners CancerCare, Boston, MA., Perou CM; Lineberger Comprehensive Center, University of North Carolina, Chapel Hill, NC.; Department of Genetics, University of North Carolina, Chapel Hill, NC., Carey LA; Lineberger Comprehensive Center, University of North Carolina, Chapel Hill, NC.; Division of Hematology-Oncology, University of North Carolina, Chapel Hill, NC.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2020 Dec 10; Vol. 38 (35), pp. 4184-4193. Date of Electronic Publication: 2020 Oct 23.
DOI:	10.1200/JCO.20.01276
Abstrakt:	Purpose: CALGB 40601 assessed whether dual versus single human epidermal growth factor receptor 2 (HER2) -targeting drugs added to neoadjuvant chemotherapy increased pathologic complete response (pCR). Here, we report relapse-free survival (RFS), overall survival (OS), and gene expression signatures that predict pCR and survival. Patients and Methods: Three hundred five women with untreated stage II and III HER2-positive breast cancer were randomly assigned to receive weekly paclitaxel combined with trastuzumab plus lapatinib (THL), trastuzumab (TH), or lapatinib (TL). The primary end point was pCR, and secondary end points included RFS, OS, and gene expression analyses. mRNA sequencing was performed on 264 pretreatment samples. Results: One hundred eighteen patients were randomly allocated to THL, 120 to TH, and 67 to TL. At more than 7 years of follow-up, THL had significantly better RFS and OS than did TH (RFS hazard ratio, 0.32; 95% CI, 0.14 to 0.71; P = .005; OS hazard ratio, 0.34; 95% CI, 0.12 to 0.94; P = .037), with no difference between TH and TL. Of 688 previously described gene expression signatures, significant associations were found in 215 with pCR, 45 with RFS, and only 22 with both pCR and RFS (3.2%). Specifically, eight immune signatures were significantly correlated with a higher pCR rate and better RFS. Among patients with residual disease, the immunoglobulin G signature was an independent, good prognostic factor, whereas the HER2-enriched signature, which was associated with a higher pCR rate, showed a significantly shorter RFS. Conclusion: In CALGB 40601, dual HER2-targeting resulted in significant RFS and OS benefits. Integration of intrinsic subtype and immune signatures allowed for the prediction of pCR and RFS, both overall and within the residual disease group. These approaches may provide means for rational escalation and de-escalation treatment strategies in HER2-positive breast cancer.
Databáze:	MEDLINE
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