Clinical and Biomarker Findings of Neoadjuvant Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer: NeoPACT Phase 2 Clinical Trial.

Autor:	Sharma P; Department of Internal Medicine, University of Kansas Medical Center, Westwood., Stecklein SR; Department of Radiation Oncology, University of Kansas Medical Center, Kansas City.; Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City.; Department of Cancer Biology, University of Kansas Medical Center, Kansas City., Yoder R; The University of Kansas Cancer Center, Kansas City., Staley JM; The University of Kansas Cancer Center, Kansas City., Schwensen K; Department of Internal Medicine, University of Kansas Medical Center, Westwood., O'Dea A; Department of Internal Medicine, University of Kansas Medical Center, Westwood., Nye L; Department of Internal Medicine, University of Kansas Medical Center, Westwood., Satelli D; Department of Internal Medicine, University of Kansas Medical Center, Westwood., Crane G; Department of Internal Medicine, University of Kansas Medical Center, Westwood., Madan R; Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City., O'Neil MF; Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City., Wagner J; Department of Surgery, University of Kansas Medical Center, Kansas City., Larson KE; Department of Surgery, University of Kansas Medical Center, Kansas City., Balanoff C; Department of Surgery, University of Kansas Medical Center, Kansas City., Kilgore L; Department of Surgery, University of Kansas Medical Center, Kansas City., Phadnis MA; Department of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City., Godwin AK; Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City.; The University of Kansas Cancer Center, Kansas City., Salgado R; Department of Pathology, ZAS Hospitals, Antwerp, Belgium.; Division of Research, Peter Mac Callum Canter Centre, Melbourne, Australia., Khan QJ; Department of Internal Medicine, University of Kansas Medical Center, Westwood., O'Shaughnessy J; Baylor University Medical Center, Dallas, Texas.
Jazyk:	angličtina
Zdroj:	JAMA oncology [JAMA Oncol] 2024 Feb 01; Vol. 10 (2), pp. 227-235.
DOI:	10.1001/jamaoncol.2023.5033
Abstrakt:	Importance: Addition of pembrolizumab to anthracycline-based chemotherapy improves pathologic complete response (pCR) and event-free survival (EFS) in triple-negative breast cancer (TNBC). The efficacy of anthracycline-free chemoimmunotherapy in TNBC has not been assessed. Objective: To assess the efficacy of the anthracycline-free neoadjuvant regimen of carboplatin and docetaxel plus pembrolizumab in TNBC. Design, Setting, and Participants: This was an open-label phase 2 clinical trial including a single group of patients with stage I to III TNBC enrolled at 2 sites who received neoadjuvant carboplatin and docetaxel plus pembrolizumab every 21 days for 6 cycles. Participants were enrolled from 2018 to 2022. Intervention or Exposure: Carboplatin (with an area under the free carboplatin plasma concentration vs time curve of 6) and docetaxel (75 mg/m2) plus pembrolizumab (200 mg) every 21 days for 6 cycles. Myeloid growth factor support was administered with all cycles. Main Outcomes and Measures: Primary end point was pathologic complete response (pCR) defined as no evidence of invasive tumor in breast and axilla. The secondary end points were residual cancer burden, EFS, toxicity, and immune biomarkers. RNA isolated from pretreatment tumor tissue was subjected to next-generation sequencing. Specimens were classified as positive or negative for the 44-gene DNA damage immune response (DDIR) signature and for the 27-gene tumor immune microenvironment (TIM; DetermaIO) signature using predefined cutoffs. Stromal tumor-infiltrating lymphocytes (sTILs) were evaluated using standard criteria. Programmed cell death-ligand 1 (PD-L1) testing was performed using a standard immunohistochemical assay. Results: Among the eligible study population of 115 female patients (median [range] age, 50 [27-70] years) who enrolled from September 2018 to January 2022, 39% had node-positive disease. pCR and residual cancer burden 0 + 1 rates were 58% (95% CI, 48%-67%) and 69% (95% CI, 60%-78%), respectively. Grade 3 or higher immune-mediated adverse events were observed in 3.5% of patients. sTILs, PD-L1, DDIR, and TIM were each predictive of pCR in multivariable analyses. The areas under curve for pCR were 0.719, 0.740, 0.699, and 0.715 for sTILs, PD-L1, DDIR, and TIM, respectively. Estimated 3-year EFS was 86% in all patients; 98% in pCR group and 68% in no-pCR group. Conclusions and Relevance: The findings of the phase 2 clinical trial indicate that neoadjuvant carboplatin and docetaxel plus pembrolizumab shows encouraging pCR and 3-year EFS. The regimen was well tolerated, and immune enrichment as identified by various biomarkers was independently predictive of pCR. These results provide data on an alternative anthracycline-free chemoimmunotherapy regimen for patients who are not eligible for anthracycline-based regimens and support further evaluation of this regimen as a chemotherapy de-escalation strategy in randomized studies for TNBC. Trial Registration: ClinicalTrials.gov Identifier: NCT03639948.
Databáze:	MEDLINE
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