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Clinical Trial
. 2024 Oct 1;116(10):1654-1663.
doi: 10.1093/jnci/djae129.

Neoadjuvant pembrolizumab plus chemotherapy/adjuvant pembrolizumab for early-stage triple-negative breast cancer: quality-of-life results from the randomized KEYNOTE-522 study

Rebecca Dent  1 , Javier Cortés  2   3   4   5 , Lajos Pusztai  6 , Heather McArthur  7 , Sherko Kümmel  8   9 , Jonas Bergh  10 , Carsten Denkert  11 , Yeon Hee Park  12 , Rina Hui  13   14 , Nadia Harbeck  15 , Masato Takahashi  16 , Michael Untch  17 , Peter A Fasching  18 , Fatima Cardoso  19 , Amin Haiderali  20 , Liyi Jia  21 , Allison Martin Nguyen  22 , Wilbur Pan  23 , Joyce O'Shaughnessy  24 , Peter Schmid  25
Affiliations
Clinical Trial

Neoadjuvant pembrolizumab plus chemotherapy/adjuvant pembrolizumab for early-stage triple-negative breast cancer: quality-of-life results from the randomized KEYNOTE-522 study

Rebecca Dent et al. J Natl Cancer Inst. .

Abstract

Background: In KEYNOTE-522 (NCT03036488), neoadjuvant pembrolizumab plus chemotherapy and then adjuvant pembrolizumab significantly improved pathological complete response and event-free survival vs neoadjuvant chemotherapy in early-stage triple-negative breast cancer (TNBC). We report patient-reported outcomes (PROs) from KEYNOTE-522.

Methods: Patients were randomized 2:1 to neoadjuvant pembrolizumab 200 mg or placebo every 3 weeks, plus 4 cycles of paclitaxel plus carboplatin and then 4 cycles of doxorubicin (or epirubicin) plus cyclophosphamide. After surgery, patients received adjuvant pembrolizumab or placebo for up to 9 cycles. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EORTC Breast Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23) were prespecified secondary objectives. Between-group differences in least squares (LS) mean change from baseline (day 1 of cycle 1 in both neoadjuvant and adjuvant phases) to the prespecified latest time point with at least 60% completion and at least 80% compliance were assessed using a longitudinal model (no alpha error assigned).

Results: Week 21 (neoadjuvant phase) and week 24 (adjuvant phase) were the latest time points at which completion/compliance rates were ≥60%/80%. In the neoadjuvant phase, between-group differences (pembrolizumab plus chemotherapy [n = 762] vs placebo plus chemotherapy [n = 383]) in LS mean change from baseline to week 21 in QLQ-C30 global health status/quality of life (GHS/QoL), emotional functioning, and physical functioning were -1.04 (95% confidence interval = -3.46 to 1.38), -0.69 (95% CI = -3.13 to 1.75), and -2.85 (95% CI = -5.11 to -0.60), respectively. In the adjuvant phase, between-group differences (pembrolizumab [n = 539] vs placebo [n = 308]) in LS mean change from baseline to week 24 were -0.41 (95% CI = -2.60 to 1.77), -0.60 (95% CI = -2.99 to 1.79), and -1.57 (95% CI = -3.36 to 0.21).

Conclusions: No substantial differences in PRO assessments were observed between neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab vs neoadjuvant placebo plus chemotherapy in early-stage TNBC.

Trial registration: ClinicalTrials.gov, NCT03036488.

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Conflict of interest statement

R. Dent: Advisory/Consultancy: AstraZeneca, Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Pfizer, Roche.

J. Cortés: Honoraria (self), Advisory/Consultancy, Research Grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: Celgene, Lilly; Honoraria (self), Research Grant/Funding (institution), Travel/Accommodation/Expenses: Eisai, Pfizer; Honoraria (self): Samsung Bioepis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Advisory/Consultancy: Atenex, Biothera Pharmaceuticals, Cellestia, Erytech, Merus, Polyphor, Seattle Genetics, Servier; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Research Grant/Funding (institution): Ariad Pharmaceuticals, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Guardian Health, Piqur Therapeutics, Puma C, Queen Mary University of London, Seagen; Shareholder/Stockholder/Stock Options: MedSIR.

L. Pusztai: Honoraria (self), Advisory/Consultancy, Research Grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca, Merck & Co., Inc., Rahway, NJ, USA, Seattle Genetics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Almac, Eisai, Genentech, Immunomedics, Novartis, Pieris, Syndax.

H. McArthur: Consultancy: AstraZeneca, Bristol Myers Squibb, Crown Bioscience, Daiichi-Sankyo, Eli Lilly, Gilead, Pfizer, Puma, Seattle Genetics, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Research Support: Bristol Myers Squibb, BTG, LLC/AstraZeneca, MedImmune, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

S. Kümmel: Advisory/Consultancy: Agendia, Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Genomic Health, Gilead Sciences, Hologic, Lilly, Novartis, Pfizer, PFM Medical, Roche/Genetech, Seagen, Somatex, Sonoscape, Stryker, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Travel/Accommodation/Expenses: Daiichi Sankyo, Gilead Sciences, Roche; Uncompensated relationships: WSG Study Group.

J. Bergh: Research Grant/Funding (institution): Amgen, AstraZeneca, Bayer, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Pfizer, Roche, Sanofi Aventis; Chapter Honoraria: from UpToDate to Asklepios Medicin Hb. Stocks: Stratipath AB, Coronis, Asklepios Cancer Research AB.

C. Denkert: Honoraria (self): Novartis, Pfizer, Roche, Teva; Honoraria (self), Advisory/Consultancy: Amgen; Advisory/Consultancy: Daichi Sankyo, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Licensing/Royalties: VmScope.

Y.H. Park: Consultancy or Advisory Board Member: AstraZeneca, Eisai, Novartis, Pfizer, Roche; Research Funding: Alteogen, AstraZeneca, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Roche.

R. Hui: Personal Fees for Advisory Boards: Amgen, AstraZeneca, BMS, Eisai, Eli Lilly, Merck KGaA, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Oncosec, Pfizer, Roche, Seagen, Takeda, Zai Lab; Speaker Honoraria: AstraZeneca, Eli Lilly, Janssen, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Roche; Study Funding (institution): AstraZeneca, BMS, Corvus, Eisai, Eli Lilly, Janssen, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Oncosec, Roche, Seagen.

N. Harbeck: Stock and Other Ownership Interests: West German Study Group; Honoraria: Amgen, AstraZeneca, Daiichi Sankyo, Gilead, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, Seagen, Viatris, Zuelligpharma; Consulting or Advisory Role: Gilead, Roche, Sandoz, Seagen; Research Funding (institution): Lilly, Novartis, Pfizer, Roche/Genentech, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

M. Takahashi: Honoraria (self): AstraZeneca, Lilly, Pfizer; Honoraria (self), Research Grant/Funding (self): Eisai; Research Grant/Funding (self): Kyowa-Hakko Kirin, Nippon Kayaku, Taiho.

M. Untch: Consulting Fees (institution): Abbvie, Amgen, AstraZeneca, Daiichi Sankyo, Gilead, GSK, Lilly, Molecular Health, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Myriad, Novartis, Pfizer, Pierre Fabre, Roche, Menarini Stemline, CD Pharma, Agendia, Seagen; Honoraria Speaker (institution): Abbvie, AstraZeneca, Daiichi Sankyo, Gilead, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Myriad, Novartis, Pfizer, Pierre Fabre, Roche, Menarini Stemline, Seagen.

P.A. Fasching: Consulting Fees: Agendia, AstraZeneca, Daiichi Sankyo, Eisai, Hexal, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Pierre Fabre, Roche, Seagen; Fees for Non-CME Services Received Directly from Commercial Interest or their Agents: Daiichi Sankyo, Lilly, Novartis, Seagen; Research Grant: Biontech, Cepheid.

F. Cardoso: Consultancy/Advisory Role: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, Genentech, GE Oncology, Gilead, GlaxoSmithKline, Iqvia, Macrogenics, Medscape, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Merck & Co., Inc., Rahway, NJ, USA, Merus BV, Mundipharma, Mylan, Novartis, Pfizer, Pierre-Fabre, prIME Oncology, Roche, Samsung Bioepis, Sanofi, Seagen, Teva, Touchime.

A. Haiderali, L. Jia, A.M. Nguyen, and W. Pan: Employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and stockholders in Merck & Co., Inc., Rahway, NJ, USA.

J. O’Shaughnessy: Consulting Fees: AbbVie, Agendia, Amgen, Aptitude Health, AstraZeneca, Bayer, BMS, Celgene, Clovis Oncology, Daiichi Sankyo, Eisai, G1 Therapeutics, Genentech, Gilead Sciences, GRAIL, Halozyme, Heron Therapeutics, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Myriad, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, Pierre Fabre, Prime Oncology, Puma Biotechnology, Roche, Samsung Bioepis, Sanofi, Seagen, Syndax Pharmaceuticals, Synthon, Taiho Oncology, Takeda.

P. Schmid: Consultant/Honoraria: AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Eisai, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Puma, Roche; Grant Funding (institution): Astellas, AstraZeneca, Genentech, Medivation, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Oncogenex, Roche.

Figures

Figure 1.
Figure 1.
Patient disposition. EQ-5D = EuroQol 5-Dimension Questionnaire; PRO = patient-reported outcome; QLQ-BR23 = European Organisation for Research and Treatment of Cancer Breast Cancer–Specific Quality of Life Questionnaire; QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30.
Figure 2.
Figure 2.
Change from baseline to week 21 in the neoadjuvant phase: A) QLQ-C30 GHS/QoL and functional scales, B) QLQ-C30 symptom scales or items, C) QLQ-BR23 functional scales or items, and D) QLQ-BR23 symptom scales or items. For GHS/QoL score and all functional scales, a higher score denotes better HRQoL or function. For symptoms scales or items, a higher score denotes worse symptoms. CI = confidence interval; GHS/QoL = global health status/quality of life; HRQoL = health-related quality of life; LS = least squares; QLQ-BR23 = European Organisation for Research and Treatment of Cancer Breast Cancer–Specific Quality of Life Questionnaire; QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30.
Figure 3.
Figure 3.
Change from baseline to week 24 in the adjuvant phase: A) QLQ-C30 GHS/QoL and functional scales, B) QLQ-C30 symptom scales or items, C) QLQ-BR23 functional scales or items, and D) QLQ-BR23 symptom scales or items. For GHS/QoL score and all functional scales, a higher score denotes better HRQoL or function. For symptoms scales or items, a higher score denotes worse symptoms. CI = confidence interval; GHS/QoL = global health status/quality of life; HRQoL = health-related quality of life; LS = least squares; QLQ-BR23 = European Organisation for Research and Treatment of Cancer Breast Cancer–Specific Quality of Life Questionnaire; QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30.
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References

    1. Howlader N, Cronin KA, Kurian AW, Andridge R.. Differences in breast cancer survival by molecular subtypes in the United States. Cancer Epidemiol Biomarkers Prev. 2018;27(6):619-626. - PubMed
    1. National Cancer Institute. Cancer Stat Facts: Female Breast Cancer Subtypes. https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed December 13, 2022.
    1. Haiderali A, Rhodes WC, Gautam S, et al.Real-world treatment patterns and effectiveness outcomes in patients with early-stage triple-negative breast cancer. Future Oncol. 2021;17(29):3819-3831. - PubMed
    1. Howard FM, Pearson AT, Nanda R.. Clinical trials of immunotherapy in triple-negative breast cancer. Breast Cancer Res Treat. 2022;195(1):1-15. - PMC - PubMed
    1. Schmid P, Salgado R, Park YH, et al.Pembrolizumab plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: results from the phase 1b open-label, multicohort KEYNOTE-173 study. Ann Oncol. 2020;31(5):569-581. - PubMed

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