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Clinical Trial
. 2024 Feb 1;10(2):227-235.
doi: 10.1001/jamaoncol.2023.5033.

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

Priyanka Sharma  1 , Shane R Stecklein  2   3   4 , Rachel Yoder  5 , Joshua M Staley  5 , Kelsey Schwensen  1 , Anne O'Dea  1 , Lauren Nye  1 , Deepti Satelli  1 , Gregory Crane  1 , Rashna Madan  3 , Maura F O'Neil  3 , Jamie Wagner  6 , Kelsey E Larson  6 , Christa Balanoff  6 , Lyndsey Kilgore  6 , Milind A Phadnis  7 , Andrew K Godwin  3   5 , Roberto Salgado  8   9 , Qamar J Khan  1 , Joyce O'Shaughnessy  10
Affiliations
Clinical Trial

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

Priyanka Sharma et al. JAMA Oncol. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Sharma reported research funding from Merck, Novartis, and Bristol Myers Squibb, royalties from UpToDate, and personal fees from Novartis, Merck, AstraZeneca, Pfizer, Gilead, GlaxoSmithKline, and Sanofi outside the submitted work. Dr O’Dea reported consulting/speaking fees and honoraria from Pfizer, Novartis, Eli Lilly, PUMA Biotechnology, Astra Zeneca, Daiichi Sankyo, Stemline, and Gilead, all outside the submitted work. Dr Nye reported advisory board membership for Myriad outside the submitted work. Dr Godwin reported grants from Predicine and VITRAC Therapeutics during the conduct of the study and being a Sinochips Diagnostics cofounder and scientific advisory board member outside the submitted work. Dr Salgado reported advisory board membership for Roche and Exact Sciences, and research report from Merck, Bristol Myers Squibb, Owkin, and Puma Biotechnology outside the submitted work. Dr O’Shaughnessy reported advisory board and/or consulting fees from Agendia, Aptitude Health, Daiichi Sankyo Consulting, Eisai, G1 Therapeutics, Genentech, Gilead, Eli Lilly, Loxo Oncology, Merck, Novartis, Ontada, Pfizer, Pierre Fabre Pharmaceuticals, Puma Biotechnology, Roche, Samsung Bioepis, Sanofi, Seagen, Stemline Therapeutics and Synthon, all outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram of Study Participants
ER refers to estrogen receptor.
Figure 2.
Figure 2.. Event-Free Survival (EFS) of Patients in the Intent-to-Treat Group (N = 115)
HR indicates hazard ratio, and pCR, pathologic complete response.
See this image and copyright information in PMC

References

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