Abstract 169P
Background
Neoadjuvant pembrolizumab + chemotherapy (paclitaxel + carboplatin followed by anthracycline + cyclophosphamide) followed by adjuvant pembrolizumab received FDA approval for patients with high-risk, early-stage triple-negative breast cancer (eTNBC) based on improvements in pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy in the phase III randomized controlled trial (RCT) KEYNOTE-522. Network meta-analysis (NMA) allows the efficacy of pembrolizumab + chemotherapy / pembrolizumab relative to other treatments to be estimated in the absence of head-to-head RCT evidence.
Methods
A systematic literature review was conducted in July 2021 to identify eligible RCTs of neoadjuvant treatments with or without adjuvant treatment for patients with high-risk eTNBC. Fixed-effects Bayesian NMA was used to synthesize odds ratios (ORs) for pCR and hazard ratios (HRs) for EFS along with 95% credible intervals (CrIs).
Results
The distribution of relative treatment effect modifiers was balanced across the five included RCTs. Only KEYNOTE-522 included treatments in both neoadjuvant and adjuvant settings. For pCR, pembrolizumab + chemotherapy / pembrolizumab was statistically superior to paclitaxel + carboplatin followed by anthracycline + cyclophosphamide (OR: 1.36; 95% CrI: 1.06-1.73), paclitaxel followed by anthracycline + cyclophosphamide (OR: 3.12; 95% CrI: 2.04-4.85), and paclitaxel + bevacizumab followed by anthracycline + cyclophosphamide + bevacizumab (OR: 1.89; 95% Crl: 1.07-3.30). For EFS, pembrolizumab + chemotherapy / pembrolizumab was numerically superior to all comparators and statistically superior to paclitaxel + carboplatin followed by anthracycline + cyclophosphamide (HR: 0.63; 95% CrI: 0.48-0.82), paclitaxel followed by anthracycline + cyclophosphamide (HR: 0.36; 95% CrI: 0.21-0.61), and paclitaxel + carboplatin + veliparib followed by anthracycline + cyclophosphamide (HR: 0.57; 95% Crl: 0.34-0.95).
Conclusions
These results indicate pembrolizumab + chemotherapy / pembrolizumab is an effective treatment relative to other interventions for treatment of high-risk eTNBC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Merck & Co., Inc.
Funding
Merck & Co., Inc.
Disclosure
J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, Astrazeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, MERCK SHARP& DOHME, GSK, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MERCK SHARP& DOHME, Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, Astrazeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo. A. Haiderali: Financial Interests, Institutional, Full or part-time Employment, Amin Haiderali is an employee of Merck & Co., Inc., the manufacturer of pembrolizumab.: Merck & Co., Inc. M. Huang: Financial Interests, Institutional, Full or part-time Employment, Min Huang is an employee of Merck & Co., Inc., the manufacturer of pembrolizumab.: Merck & Co., Inc. W. Pan: Financial Interests, Institutional, Full or part-time Employment, Wilbur Pan is an employee of Merck & Co., Inc., the manufacturer of pembrolizumab.: Merck & Co., Inc. G.E. Fox: Financial Interests, Institutional, Funding, Grace E. Fox is an employee of PRECISIONheor, a healthcare research consultancy that received funding from Merck & Co., Inc. for completion of this research.: PRECISIONheor. J. Park: Financial Interests, Institutional, Funding, Julie Park is an employee of PRECISIONheor, a healthcare research consultancy that received funding from Merck & Co., Inc. for completion of this research.: PRECISIONheor. A.M. Frederickson: Financial Interests, Institutional, Funding, Andrew Frederickson is an employee of PRECISIONheor, a healthcare research consultancy that received funding from Merck & Co., Inc. for completion of this research.: PRECISIONheor. P.A. Fasching: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, Astrazeneca, Hecal, Lilly, Pierre Fabre, Seagen, Agendia; Financial Interests, Personal, Invited Speaker: Novartis, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Lilly, Seagen; Financial Interests, Personal, Other, Medical Writing Support: Roche; Financial Interests, Institutional, Invited Speaker: BionTech, Cepheid; Non-Financial Interests, Member: ASCO, Arbeitsgemeinschaft für Gynäkologische Onkologie e.V., Translational Research in Oncology, Deutsche Gesellschaft für Senologie e.v. J. O'Shaughnessy: Financial Interests, Personal, Advisory Board: AbbVie, Agendia, Amgen, Aptitude Health, AstraZeneca, Bristol-Myers Squibb, Celgene, Eisai, G1 Therapeutics, Genentech, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Novartis, Ondonate, Pfizer, Puma, Prime Oncology, Roche, Seattle Genetics, Syndax, Carrick Therapeutics, Daiichi Sankyo, Gilead Sciences, Ontada, Pierre Fabre Pharmaceuticals, Samsung Bioepis, Sanofi.