Higher serum PD‐L1 level predicts increased overall survival with lapatinib versus trastuzumab in the CCTG MA.31 phase 3 trial
Autor: | Dora Nomikos, Liting Zhu, Karen A. Gelmon, Prashanth Reddy Moku, E. Scott Halstead, Samuel Aparicio, Joyson Poulose, Ashok Maddukuri, Kim Leitzel, Allan Lipton, Shakeel Virk, Vinod Nagabhairu, Todd Umstead, Howard Spiegel, Dan Mckeone, Bingshu E. Chen, Wendy R. Parulekar, Leah Cream, Lois E. Shepherd, Hyma Polimera, Suhail M. Ali, Neha Pancholy, Joseph J. Drabick, Aamnah Ali |
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Rok vydání: | 2020 |
Předmět: |
Oncology
Cancer Research medicine.medical_specialty Receptor ErbB-2 Population Breast Neoplasms Lapatinib B7-H1 Antigen 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine Breast cancer Trastuzumab Internal medicine Biomarkers Tumor Humans Medicine 030212 general & internal medicine Neoplasm Metastasis skin and connective tissue diseases education Randomized Controlled Trials as Topic Retrospective Studies education.field_of_study business.industry Hazard ratio Cancer medicine.disease Metastatic breast cancer Progression-Free Survival Clinical Trials Phase III as Topic 030220 oncology & carcinogenesis Biomarker (medicine) Female business medicine.drug |
Zdroj: | Cancer. 126:4859-4866 |
ISSN: | 1097-0142 0008-543X |
Popis: | Background The purpose of this retrospective biomarker study of the Canadian Cancer Trials Group (CCTG) MA.31 randomized phase 3 trial (lapatinib vs trastuzumab) of HER2-positive metastatic breast cancer (MBC) was to evaluate the prognostic and predictive biomarker utility of pretreatment serum programmed death ligand 1 (PD-L1) levels. Methods CCTG MA.31 accrued 652 HER2-positive patients; 387 had serum available (185 in the trastuzumab arm and 202 in the lapatinib arm). The Ella immunoassay platform (ProteinSimple, San Jose, California) was used to quantitate serum PD-L1 levels. Stepwise forward Cox multivariable analyses were performed for progression-free survival and overall survival (OS). Results In the whole trial population, continuous pretreatment serum PD-L1 levels were not associated with OS. However, within the trastuzumab arm, a higher continuous pretreatment serum PD-L1 level was significant for shorter OS (hazard ratio [HR], 3.85; P = .04), but within the lapatinib arm, pretreatment serum PD-L1 was not associated with OS (P = .37). In the whole trial, in a multivariable analysis for OS, serum PD-L1 (median cut point) remained a significant independent covariate (HR, 2.38; P = .001). There was a significant interaction between treatment arm and continuous serum PD-L1 (bootstrap method; P = .0025): at or above 214.2 pg/mL (the 89th percentile), serum PD-L1 was associated with significantly shorter OS with trastuzumab treatment versus lapatinib treatment. Conclusions In the CCTG MA.31 trial, serum PD-L1 was a significant predictive factor: a higher pretreatment serum PD-L1 level was associated with shorter OS with trastuzumab treatment but with longer OS with lapatinib treatment. Immune evasion may decrease the effectiveness of trastuzumab therapy. Further evaluation of elevated serum PD-L1 in advanced breast cancer is warranted to identify patients with HER2-positive MBC who may benefit from novel immune-targeted therapies in addition to trastuzumab. |
Databáze: | OpenAIRE |
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