Immunotherapy related patient-reported outcomes from five randomized controlled trials in patients with triple negative breast cancer: A systematic review.

Abstract

e23167 Background: Immunotherapy (IO) has improved clinical outcomes in patients with early-stage Triple Negative Breast Cancer (TNBC) receiving neoadjuvant therapy and certain patient subsets in the metastatic setting. This study aims to evaluate IO-related Patient-Reported Outcomes (PRO) in patients older than 65 years. Methods: We searched Medline ALL (Ovid), Embase (Elsevier), Cochrane Central (Wiley), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. The searches combined terms reflecting (1) the immune checkpoint inhibitors atezolizumab, durvalumab, and pembrolizumab; (2) breast cancer; and (3) randomized controlled trials. Results were limited to items published in English from 2013 through September 2023. We excluded review articles and clinical trial records without results. Two independent reviewers (C.S. and M.L.) screened the studies using the systematic review management tool Covidence, and conflicts were resolved by a third reviewer (W.I.Z.). We included studies that reported on PRO in adults with TNBC receiving any of the three immunotherapies of interest. Results: Five publications composed of two peer-reviewed papers and three abstracts were identified, including 3878 total patients and 3184 with PRO. Three pembrolizumab studies had 2643 total patients (2056 with PRO) and two atezolizumab studies (IMPASSION 130, IMPASSION 031) had 1235 total patients (1128 with PRO). The PRO analysis in KEYNOTE 522 included 1145 patients in the neoadjuvant phase and 847 in the adjuvant phase. The PRO analysis in KEYNOTE 355 included total 847 patients and 317 with Combined Positive Score (CPS) ≥10. No study specified PRO data for patients older than 65 years. Baseline completion rates for all studies were > 80%. All studies used standardized PRO instruments, including the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC- QLQ C30) and its Breast Cancer Module (QLQ-BR23), the Functional Assessment of Cancer-Therapy-General (FACT-G GP5), and the EuroQol-5 Dimension (EQ-D5). All studies showed no statistical difference, or clinical meaningful decline in PRO endpoints between patients who received chemo with IO versus chemo with placebo, during and post treatment follow up. The PRO analysis from KEYNOTE 119, which included total 594 patients of which 187 had CPS ≥10, demonstrated that patients receiving single agent chemotherapy had worse PROs related to systemic therapy side effects and hair loss while the pembrolizumab group had decreased worry about future health. None included subgroup analysis by age, including patients older than 65 years. Conclusions: Our systematic review demonstrates that in both early and advanced TNBC, IO did not worsen PRO. Prospective and retrospective data in IO-related PRO in older patient population are needed.