Combination therapy improves PFS in NSCLC
Combining the monoclonal antibody atezolizumab with a carboplatin-paclitaxel chemotherapy regimen and the biologic antiangiogenic agent bevacizumab led to a significant progression-free survival (PFS) benefit in chemotherapy-naïve patients with non-squamous metastatic non-small-cell lung cancer (mNSCLC), according to the IMpower150* trial presented at ELCC 2018.
A total of 1,202 patients received chemotherapy (6AUC** carboplatin and paclitaxel 200 mg/m2) either with atezolizumab 1,200 mg (group 1), atezolizumab and bevacizumab 15 mg/kg (group 2), or bevacizumab (group 3). The ITT*** wild-type (WT) sample included EGFR- or ALK-negative participants from groups 2 and 3 (median age 63 years, n=356 and 336, respectively), while the T-effector (TEFF) WT population included those with expression of a tumour TEFF gene signature (n=155 and 129, respectively). [ELCC 2018, abstract 134PD]
The study drugs were administered intravenously every three weeks for four or six cycles depending on investigator’s discretion. Maintenance regimen included atezolizumab or bevacizumab for groups 1 and 3, respectively, and both for group 2.
Median PFS was superior in group 2 vs group 3 in both the ITT-WT and the TEFF-WT populations (8.3 vs 6.8 months, hazard ratio [HR], 0.62, 95 percent confidence interval [CI], 0.52–0.74; p<0.0001 and 11.3 vs 6.8 months, HR, 0.51, 95 percent CI, 0.38–0.68; p<0.0001, respectively).
PFS benefit remained consistent regardless of PD-L1 immunohistochemistry status, including PD-L1-negative patients (TC0/IC0#, HR, 0.77, 95 percent CI, 0.61–0.99).
Higher objective response rates were observed in group 2 vs group 3 (64.0 percent vs 48.0 percent and 69.0 percent vs 54.0 percent in the ITT-WT and TEFF-WT populations, respectively).
Safety profile was comparable between groups 2 and 3 (25 percent vs 19 percent treatment-related serious adverse events, respectively).
The clinically relevant survival benefit and lack of toxicity issues highlight the potential of targeting multiple pathways, favouring the addition of atezolizumab to bevacizumab and chemotherapy for first-line mNSCLC treatment, noted the researchers.
Atezolizumab restores anticancer immunity through PD-L1 inhibition, bevacizumab inhibits vascular endothelial growth factor-related immunosuppression and promotes T-cell tumour infiltration, while chemotherapy may induce immune responses, they added.
The association between groups 1 and 3 has not been established due to prespecified statistical testing hierarchy, noted the researchers.