Combined atezolizumab and nab-paclitaxel in the treatment of triple negative breast cancer: a meta-analysis on their efficacy and safety

Abstract

Background Triple negative breast cancer (TNBC) is clinically aggressive breast cancer with a poor prognosis. Approximately 20% of TNBC has been found to express programmed death ligand 1 (PD-L1), making it a potential therapeutic target. As a PD-L1 inhibitor, atezolizumab is a recently approved immunotherapeutic drug for TNBC, this meta-analysis (MA) was aimed to review the randomized controlled trial studies (RCTs) of combined atezolizumab and nab-paclitaxel in the treatment of TNBC and synthesize the evidence-based results on its effectiveness and safety. Method We searched PubMed, Embase, EBSCOhost and ClinicalTrials.gov for the eligible RCTs which compared the efficacy and safety of combined atezolizumab and nab-paclitaxel with nab-paclitaxel alone. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse effects (AEs). Results A total of six RCTs were included in this MA. For efficacy, although OS was not significantly prolonged with combined atezolizumab and nab-paclitaxel (HR 0.90, 95% CI [0.79, 1.01], p=0.08), this combination therapy significantly improved PFS (HR 0.72, 95% CI [0.59, 0.87], p=0.0006) and ORR (RR 1.25, 95% CI [0.79, 1.01] p<0.00001). For safety, any AEs, haematological, gastrointestinal, and liver AEs showed no statistically significant differences between the atezolizumab and nab-paclitaxel combination group and nab-paclitaxel alone group. However, serious AEs, high grade, dermatological, pulmonary, endocrine, and neurological AEs were significantly lower with nab-paclitaxel alone compared to atezolizumab and nab-paclitaxel combined (p-value range from <0.00001 to 0,02). Conclusion Atezolizumab combined with nab-paclitaxel was associated with improved outcomes in the treatment of TNBC; however, this combination resulted in more toxicity compared to nab-paclitaxel alone. While nab-paclitaxel alone produced chemotherapy-related AEs, the combination of atezolizumab with nab-paclitaxel produced AEs, especially immune-related AEs such as haematological, pulmonary, endocrine, and neurological AEs. Trial registration This research work of systematic review has been registered on PROSPERO (Registration number: CRD42022297952).

Immunogenic cell death in cancer: concept and therapeutic implications

“…Third, in line with preclinical findings, a growing number of ICD inducers positively interact with ICIs or other immunotherapeutic approaches in patients with cancer [ 79 , 80 ]. Notable examples of such successful combinations include (1) nab-paclitaxel plus atezolizumab (an ICI specific for PD-L1), which is currently employed in the management of triple negative breast cancer (TNBC) [ 81 ], carboplatin/etoposide plus atezolizumab, which is approved for patients with extensive-stage small cell lung cancer (SCLC) [ 82 ], as well nab-paclitaxel/carboplatin plus the programmed cell death 1 (PDCD1, best known as PD-1) blocker pembrolizumab [ 83 ].…”

Exploration of the Use of Natural Compounds in Combination with Chemotherapy Drugs for Tumor Treatment

“…With the in-depth research on tumor therapeutic targets, chemotherapeutic drugs with different targets and pathways of action have started to adopt a combination therapy strategy to deal with the malignant development of tumors [ 8 , 9 ]. However, considering the more serious adverse effects of chemotherapeutic drugs, the combination of chemotherapeutic drugs with less toxic natural compounds that contribute to tumor management is gradually becoming one of the new strategies for tumor treatment.…”

Adverse effects in the management of breast cancer – recent studies

“…Other non-serious irAEs such as aspartate aminotransferase (AST) elevation, hypothyroidism, pruritus, rash and fever are noted more frequently in PD-(L)1 arm than chemotherapy. According to meta-analysis, atezolizumab combined with nab-paclitaxel was related with a higher incidence of serious adverse events, dermatological, endocrine, neurological adverse effects compared with chemotherapy alone [68].…”