Background: Pathologic complete response (pCR) is a common efficacy endpoint in neoadjuvant therapy trials for triple-negative breast cancer (TNBC). Previous studies have shown that pCR is strongly associated with improved long-term survival outcomes, including event-free survival (EFS) and overall survival (OS). However, the trial-level associations between treatment effect on pCR and long-term survival outcomes are not well established. This study sought to evaluate these associations by incorporating more recent clinical trials in TNBC. Methods: A literature review identified published randomized controlled trials (RCTs) of neoadjuvant therapy for TNBC that reported results for both pCR and EFS/OS. Meta-regression models were performed to evaluate the association of treatment effect on pCR and EFS/OS. Sensitivity analyses were conducted to assess the impact of divergent study designs. Results: Ten comparisons from 8 RCTs (N=2,478 patients) were identified from the literature review. The log (odds ratio) of pCR was a significant predictor of the log (hazard ratio) of EFS (P=.003), with a coefficient of determination of 0.68 (95% CI, 0.41–0.95). There was a weaker association between pCR and OS (P=.18), with a coefficient of determination of 0.24 (95% CI, 0.01–0.77). Consistent results were found in the exploratory analysis and sensitivity analyses. Conclusions: This is the first study that has shown a trial-level association between pCR and survival outcomes in TNBC. By incorporating the most up-to-date RCTs, this study showed a significant trial-level association between pCR and EFS. A positive association between pCR and OS was also recorded.
Submitted December 16, 2019; accepted for publication February 18, 2020.
Author contributions: Study design, data collection, statistical analysis, data interpretation, manuscript composition and review: All authors.
Disclosures: Drs. Huang, Zhao, Haiderali, Karantza, and Aktan have disclosed that they are employed by Merck & Co., Inc. Dr. O’Shaughnessy has disclosed that she receives personal fees from AbbVie, Agendia, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Eisai, Genentech, Genomic Health, GRAIL, Immunomedics, Heron Therapeutics, Ipsen, Jounce, Lilly, Merck, Myriad, Novartis, Ondonate Therapeutics, Pfizer, Puma Biotechnology, Roche, Seattle Genetics, Syndax, and Nektar Therapeutics. Dr. Cortes has disclosed that he receives consultant fees from Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp & Dohme, GlaxoSmithKline, and Leuko; honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, and Daiichi Sankyo; grant/research support from Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffman-La Roche, Guardant Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma Biotechnology, Queen Mary University of London, and Seagen; and stock, patents, and intellectual property from MedSIR. Dr. Ramsey has disclosed that he receives consultant fees from Merck & Co., Inc. Dr. Briggs has disclosed that he receives consultant fees from Bayer, Janssen, Novartis, Sword Health, Amgen, Merck & Co., Inc., and Daiichi Sankyo. Ms. Qi, Dr. Gu, Dr. Xie, and Mr. Yuan have disclosed that they are employed by Analysis Group, Inc., which received consultancy fees from Merck & Co., Inc. to conduct this study. Dr. Cook has disclosed that he received grant/research support from Merck & Co., Inc. Dr. Untch has disclosed that he receives consultant fees and grant/research support from AbbVie, Amgen GmbH, AstraZeneca, Celgene GmbH, Daiichi Sankyo, Eisai GmbH, Lilly, Merck Sharp & Dohme, Mundipharma, Myriad Genetics, Odonate, Pfizer GmbH, Puma Biotechnology, Roche Pharma AG, Sanofi Aventis Deutschland GmbH, TEVA Pharmaceuticals Ind Ltd, and Novartis; and honoraria from Bristol-Myers Squibb, Lilly Deutschland, and Pierre Fabre. Dr. Schmid has disclosed that he receives consultant fees from Pfizer, AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim, Bayer, Eisai, Celgene, and Puma Biotechnology; and grant/research support from AstraZeneca, Genentech, Oncogenex, Novartis, and Astellas. Dr. Fasching has disclosed that he receives grant/research support from Novartis, Biontech, and Cepheid; and honoraria from Novartis, Roche, Pfizer, Celgene, Daiichi Sankyo, TEVA, AstraZeneca, Merck Sharp & Dohme, Myelo Therapeutics, Macrogenics, Eisai, and Puma Biotechnology.
Funding: This work was supported by funding from Merck (ID0E4JAG3421).