McGahan, L. (2019): Atezolizumab (Tecentriq®) with nab-paclitaxel (Abraxane®) for the treatment of advanced triple-negative breast cancer (aTNBC). DSD: Horizon Scanning in Oncology 87.
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In patients with triple negative breast cancer (TNBC), overexpression of programmed death ligand 1 (PD-L1) on tumour-infiltrating immune cells (IC) increases the propensity for cancer cells to evade immune surveillance. Atezolizumab (Tecentriq®), a monoclonal antibody designed to inhibit PD-L1, enables both the activation of T-cells and restoring their ability to effectively detect and destroy tumour cells.
During the phase III, IMpassion130 trial, 902 treatment-naïve advanced TNBC patients were randomised 1:1 to 840 mg atezolizumab IV or placebo IV on days 1 and 15, plus 100 mg/m2 nab-paclitaxel (Abraxane®) IV on days 1, 8, and 15 of every 28-day cycle, until disease progression or toxicity. Adding atezolizumab increased the rate of progression-free survival (PFS) by 6%, prolonged median PFS by 1.7 months, and reduced the risk of progression or death by 20% compared to chemotherapy alone. In the PD-L1-positive subgroup, adding atezolizumab increased the rate of PFS by 13%, prolonged median PFS by 2.5 months, and reduced the risk of progression or death by 38% compared to nab-paclitaxel alone. No statistically significant differences in overall survival (OS) were noted between groups (21.3 months atezolizumab- versus 17.6 months placebo combination). Combination therapy with atezolizumab increased the objective response rate (ORR) and duration of response (DOR) in the intention-to-treat (ITT) and PD-L1-positive group compared to chemotherapy alone (10% versus 16%; 1.8 months versus 3.0 months, respectively. Atezolizumab was associated with neutropenia, decreased neutrophils, peripheral neuropathy, fatigue, anaemia and immune-mediated adverse events.
Overall, adding atezolizumab to nab-paclitaxel as first-line therapy for advanced TNBC prolongs PFS and reduces the risk of progression or death. The PFS benefit of atezolizumab combination therapy over chemotherapy alone was also consistent in the PD-L1-positive subgroup. These results are consistent with previous reports suggesting first-line atezolizumab, PD-L1 expression ≥1, and >10% tumour-infiltrating IC are independently associated with increased ORR and PFS. Mature OS data and quality of life measures are needed to ensure patients achieve a clinically relevant benefit over time despite manageable toxicity. Further studies are needed to identify predictive immune biomarkers selective of responders, combination strategies that enhance tumour immunogenicity, and to determine whether these findings extend to other chemoimmunotherapy combinations.
|Item Type:||DSD: Horizon Scanning in Oncology|
|Keywords:||Triple negative breast cancer (TNBC), atezolizumab (Tecentriq®), nab-paclitaxel (Abraxane®), first-line therapy, anti-PD-L1 antibody|
|Subjects:||WB Practice of medicine > WB 300-962 Therapeutics|
WP Gynaecology > WP 800-910 Breast
QZ Pathology > QZ 200-380 Neoplasms.Cysts
QV Pharmacology, toxicology, pharmacy > QV 60-370 Pharmacology
|Series Name:||DSD: Horizon Scanning in Oncology 87|
|Deposited on:||28 Mar 2019 18:31|
|Last Modified:||28 Mar 2019 18:31|
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