First line combination therapy improves progression-free survival in advanced lung cancer

A new combination therapy for the first-line treatment of advanced non-squamous non-small-cell lung cancer (NSCLC) improves progression-free survival (PFS), according to results of the phase III IMpower150 trial presented at the ESMO Immuno Oncology Congress 2017.
“This is the first phase III trial to report on the combination of chemotherapy, antiangiogenic treatment and immunotherapy as first-line treatment for advanced non-squamous NSCLC,” said lead author Professor Martin Reck, chief oncology physician, Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Germany. “The trial met its co-primary endpoint of PFS and the preliminary results of the co-primary endpoint of overall survival (OS), although immature, look encouraging.”
There is a scientific rationale to support the combinations that have been explored in the trial. Bevacizumab may enhance the ability of atezolizumab to restore anti-cancer immunity by inhibiting vascular endothelial growth factor (VEGF)-related immunosuppression and other mechanisms while chemotherapy may induce immune responses. The chemotherapy used in the trial was carboplatin plus paclitaxel. Atezolizumab is a monoclonal antibody that inhibits programmed death-ligand 1 (PD-L1), while bevacizumab is a biologic antiangiogenic drug.
IMpower150 enrolled 1,202 patients who were randomized to one of three arms: A) chemotherapy plus atezolizumab; B) chemotherapy plus atezolizumab plus bevacizumab; or C) chemotherapy plus bevacizumab.
The PFS survival comparison was made between arms B and C and showed that the combination of atezolizumab, bevacizumab and chemotherapy was superior to bevacizumab and chemotherapy alone with a median PFS of 8.3 versus 6.8 months (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.52, 0.74; P < 0.0001) in the intention-to-treat (ITT) wild type (WT) population, which excluded patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.
The corresponding median PFS in the Teff-WT population, which included patients with defined expression of a T-effector gene signature in the tumour tissue, was 11.3 versus 6.8 months (HR 0.51; 95% CI 0.38, 0.68; P < 0.0001). PFS benefit was seen regardless of PD-L1 immunohistochemistry status, including PD-L1–negative pts (TC0/IC0: HR 0.77; 95% CI 0.61, 0.99).
There were no new safety signals with the combination therapy. Due to prespecified testing hierachy, Arm A versus C has not been formally tested yet.
Reck said: “There was a significant and clinically relevant improvement in progression-free survival favouring the addition of atezolizumab to bevacizumab and chemotherapy. The results show that there is a way to improve the efficacy of platinum-based chemotherapy in patients with advanced non-squamous NSCLC. There were no new safety signals or toxicity issues with this combination so it appears to be a feasible  approach for this group of patients.”

ESMO
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