Guillermo Villacampa1, Pablo Tolosa2, Fernando Salvador3, Rodrigo Sánchez-Bayona4, Lorea Villanueva3, Rodrigo Dienstmann5, Eva Ciruelos6, Tomas Pascual7. 1. SOLTI Breast Cancer Research Group, Barcelona, Spain; The Institute of Cancer Research, London, United Kingdom; Oncology Data Science, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. 2. SOLTI Breast Cancer Research Group, Barcelona, Spain; Hospital Universitario 12 de Octubre, Madrid, Spain. 3. SOLTI Breast Cancer Research Group, Barcelona, Spain. 4. Hospital Universitario 12 de Octubre, Madrid, Spain. 5. Oncology Data Science, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. 6. SOLTI Breast Cancer Research Group, Barcelona, Spain; Hospital Universitario 12 de Octubre, Madrid, Spain; Centro Integral Oncológico Clara Campal HM (CIOCC), Madrid, Spain. 7. SOLTI Breast Cancer Research Group, Barcelona, Spain; Department of Medical Oncology, Hospital Clinic of Barcelona, Spain; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
Abstract
INTRODUCTION: The addition of immune checkpoint inhibitors (ICI) to chemotherapy (CT) has been one of the main clinical research endeavors over the last few years in patients with metastatic triple-negative breast cancer (TNBC). Recent randomized controlled trials (RCTs) have presented heterogeneous results that have elicited discussion in the oncology community. Here we conducted a systematic review and meta-analysis to evaluate this strategy. MATERIAL AND METHODS: A systematic literature review was conducted to identify RCTs that evaluated the combination of ICI plus CT versus CT alone in untreated metastatic TNBC. Random effects models were used to estimate pooled hazard ratios (HR) and odds ratios with 95% confidence intervals (95 %CI). RESULTS: A total of three RCTs including 2,400 patients with TNBC met the eligibility criteria. Patients with PD-L1-positive tumors had a significantly better PFS with the addition of ICI (HR = 0.67; 95 %CI: 0.58-0.79) and a trend towards better OS (HR = 0.79; 95 %CI: 0.60-1.03), while no benefit was observed in patients with PD-L1-negative tumors. In the PD-L1-positive subgroup, no relevant differences were found according to taxane agent used, ECOG performance status or number of metastatic sites. However, CT naïve patients obtained a larger benefit with ICI (PFS HR = 0.53) than patients previously treated with CT in neoadjuvant/adjuvant setting (PFS HR = 0.81). The most frequent immune-related adverse events in patients receiving ICI were hypothyroidism (16%) and hyperthyroidism (4.9%). CONCLUSIONS: ICI plus CT improves PFS and OS in PD-L1-positive population. A greater benefit in CT naïve patients was observed for the PD-L1-positive population while no difference was observed between taxane regimes used.
INTRODUCTION: The addition of immune checkpoint inhibitors (ICI) to chemotherapy (CT) has been one of the main clinical research endeavors over the last few years in patients with metastatic triple-negative breast cancer (TNBC). Recent randomized controlled trials (RCTs) have presented heterogeneous results that have elicited discussion in the oncology community. Here we conducted a systematic review and meta-analysis to evaluate this strategy. MATERIAL AND METHODS: A systematic literature review was conducted to identify RCTs that evaluated the combination of ICI plus CT versus CT alone in untreated metastatic TNBC. Random effects models were used to estimate pooled hazard ratios (HR) and odds ratios with 95% confidence intervals (95 %CI). RESULTS: A total of three RCTs including 2,400 patients with TNBC met the eligibility criteria. Patients with PD-L1-positive tumors had a significantly better PFS with the addition of ICI (HR = 0.67; 95 %CI: 0.58-0.79) and a trend towards better OS (HR = 0.79; 95 %CI: 0.60-1.03), while no benefit was observed in patients with PD-L1-negative tumors. In the PD-L1-positive subgroup, no relevant differences were found according to taxane agent used, ECOG performance status or number of metastatic sites. However, CT naïve patients obtained a larger benefit with ICI (PFS HR = 0.53) than patients previously treated with CT in neoadjuvant/adjuvant setting (PFS HR = 0.81). The most frequent immune-related adverse events in patients receiving ICI were hypothyroidism (16%) and hyperthyroidism (4.9%). CONCLUSIONS: ICI plus CT improves PFS and OS in PD-L1-positive population. A greater benefit in CT naïve patients was observed for the PD-L1-positive population while no difference was observed between taxane regimes used.
Authors: Emily M J Fennell; Lucas J Aponte-Collazo; Joshua D Wynn; Kristina Drizyte-Miller; Elisa Leung; Yoshimi Endo Greer; Paul R Graves; Andrew A Iwanowicz; Hani Ashamalla; Ekhson Holmuhamedov; Henk Lang; Donald S Karanewsky; Channing J Der; Walid A Houry; Stanley Lipkowitz; Edwin J Iwanowicz; Lee M Graves Journal: Pharmacol Res Perspect Date: 2022-08