1437PD - Pooled analysis of treatment-related hypothyroidism with anti-PD-1/PD-L1 therapies in cancer patients

Abstract

BackgroundBlockade of programmed death 1 (PD-1), or its ligand, PD-L1, could restore T-cell immunity. Anti-PD-1/ or anti-PD-L1 antibodies have demonstrated promising efficacy in the treatment of cancer patients. The toxicity spectrum of PD-1/PD-L1 blockers is distinct from chemotherapy or other target agents. This study aims to investigate the overall incidence of treatment-related hypothyroidism with anti-PD-1/PD-L1 therapies in cancer patients.MethodsA systematic search of literature up to January 2016 was performed in EDLINE, EMBASE, and Cochrane databases to identify relevant clinical trials. Paired reviewers independently selected articles for inclusion and extracted data. Pooled incidence was calculated using Comprehensive Meta-analysis using fixed or random effects model depending the heterogeneity of the included studies.ResultsA total of 23 clinical trials with 5290 patients were included. The overall incidence of all- and high-grade hypothyroidism in cancer patients receiving anti-PD-1/PD-L1 therapies were 7.3% (95% CI, 5.9% to 9.1%) and 0.4% (95% CI, 0.2% to 0.7%), respectively. Adding anti-CTLA-4 antibodies to PD-1/PD-L1 blockers led to increased incidence of all-grade fatigue (16.4% vs. 6.4%, p < 0.001), but not high-grade fatigue (0.3% vs. 0.4%). When stratified by cancer type, trial phase, drug category or drug dosage, no notably differences in the incidence of hypothyroidism were seen.ConclusionsHypothyroidism is commonly seen with anti-PD-1/PD-L1 therapies in cancer patients. Early and appropriate management is required to avoid unnecessary dose reductions and transitory or definitive treatment discontinuations.Legal entity responsible for the study: Sun Yat-sen University Cancer CenterFundingNational Natural Science Funds of China (Grant No: 81372502)DisclosureAll authors have declared no conflicts of interest. BackgroundBlockade of programmed death 1 (PD-1), or its ligand, PD-L1, could restore T-cell immunity. Anti-PD-1/ or anti-PD-L1 antibodies have demonstrated promising efficacy in the treatment of cancer patients. The toxicity spectrum of PD-1/PD-L1 blockers is distinct from chemotherapy or other target agents. This study aims to investigate the overall incidence of treatment-related hypothyroidism with anti-PD-1/PD-L1 therapies in cancer patients. Blockade of programmed death 1 (PD-1), or its ligand, PD-L1, could restore T-cell immunity. Anti-PD-1/ or anti-PD-L1 antibodies have demonstrated promising efficacy in the treatment of cancer patients. The toxicity spectrum of PD-1/PD-L1 blockers is distinct from chemotherapy or other target agents. This study aims to investigate the overall incidence of treatment-related hypothyroidism with anti-PD-1/PD-L1 therapies in cancer patients. MethodsA systematic search of literature up to January 2016 was performed in EDLINE, EMBASE, and Cochrane databases to identify relevant clinical trials. Paired reviewers independently selected articles for inclusion and extracted data. Pooled incidence was calculated using Comprehensive Meta-analysis using fixed or random effects model depending the heterogeneity of the included studies. A systematic search of literature up to January 2016 was performed in EDLINE, EMBASE, and Cochrane databases to identify relevant clinical trials. Paired reviewers independently selected articles for inclusion and extracted data. Pooled incidence was calculated using Comprehensive Meta-analysis using fixed or random effects model depending the heterogeneity of the included studies. ResultsA total of 23 clinical trials with 5290 patients were included. The overall incidence of all- and high-grade hypothyroidism in cancer patients receiving anti-PD-1/PD-L1 therapies were 7.3% (95% CI, 5.9% to 9.1%) and 0.4% (95% CI, 0.2% to 0.7%), respectively. Adding anti-CTLA-4 antibodies to PD-1/PD-L1 blockers led to increased incidence of all-grade fatigue (16.4% vs. 6.4%, p < 0.001), but not high-grade fatigue (0.3% vs. 0.4%). When stratified by cancer type, trial phase, drug category or drug dosage, no notably differences in the incidence of hypothyroidism were seen. A total of 23 clinical trials with 5290 patients were included. The overall incidence of all- and high-grade hypothyroidism in cancer patients receiving anti-PD-1/PD-L1 therapies were 7.3% (95% CI, 5.9% to 9.1%) and 0.4% (95% CI, 0.2% to 0.7%), respectively. Adding anti-CTLA-4 antibodies to PD-1/PD-L1 blockers led to increased incidence of all-grade fatigue (16.4% vs. 6.4%, p < 0.001), but not high-grade fatigue (0.3% vs. 0.4%). When stratified by cancer type, trial phase, drug category or drug dosage, no notably differences in the incidence of hypothyroidism were seen. ConclusionsHypothyroidism is commonly seen with anti-PD-1/PD-L1 therapies in cancer patients. Early and appropriate management is required to avoid unnecessary dose reductions and transitory or definitive treatment discontinuations.Legal entity responsible for the study: Sun Yat-sen University Cancer Center Hypothyroidism is commonly seen with anti-PD-1/PD-L1 therapies in cancer patients. Early and appropriate management is required to avoid unnecessary dose reductions and transitory or definitive treatment discontinuations.