Table 2.
Atezolizumab in advanced non-small-cell lung cancer: trials with published or presented data
| Study | Study population | Treatment arm(s) | Primary outcome(s) |
|---|---|---|---|
| Phase I | |||
| Horn et al14 | Advanced pretreated NSCLC, regardless PD-L1 expression 88 pts evaluable for activity and safety | Atezolizumab ≥20 mg/kg q3w | • Overall population: ORR 21%, mDOR 67 weeks |
| Liu et al23 | Advanced NSCLC patients regardless PD-L1 expression, candidate to first-line treatment combination of atezolizumab and platinum-based chemotherapy 76 pts evaluable for safety and activity | Atezolizumab 15 mg/kg plus Arm C: carboplatin/paclitaxel Arm D: carboplatin/pemetrexed Arm E: carboplatin/nab-paclitaxel |
Acceptable safety profile • Arm C ORR: 36%, mPFS 7.1 mo, mOS 12.9 mo • Arm D ORR: 64%, mPFS 8.4, mOS 19.3 mo • Arm E ORR: 46%, mPFS 5.7, mOS 14.8 mo |
| Kim et al25 | Advanced NSCLC ALK-positive regardless PD-L1 status candidate to first-line therapy with ALK-TKI 21 pts evaluated for safety and tolerability | Alectinib 600 mg BID for 7 days followed by alectinib 600 mg BID and atezolizumab 1,200 mg q3w | No grade 4–5 adverse events ORR 81% Median PFS 21.7 mo, median DOR 20.3 mo |
| Phase II | |||
| Spigel et al, FIR trial15 | Stage IIIB/IV NSCLC PD-L1-positive patients. 3 cohorts: 1) chemo-naive patients; 2) ≥2 line patients without brain metastases; 3) ≥2 line patients with asymptomatic treated brain metastases 138 pts (137 evaluable for efficacy) | Atezolizumab 1,200 mg q3w | • Overall population: 1) cohort ORR 29%; 2) cohort ORR 19%; 3) cohort ORR 23% |
| Peters et al, BIRCH trial17 | Stage IIIB/IV NSCLC patients with PD-L1 positivity. 3 cohorts: 1) first-line (139 pts); 2) second-line (268 pts); 3) third-line (252 pts) | Atezolizumab 1,200 mg q3w | • Overall population: 1) cohort ORR 22%; 2) cohort ORR 19%; 3) cohort ORR 18% |
| Fehrenbacher et al, POPLAR trial19 | Stage IIIB/IV NSCLC patients progressed to one line of platinum-based chemotherapy, regardless PD-L1 expression (287 pts) | Atezolizumab 1,200 mg q3w or docetaxel 75 mg/m2 q3w | • Overall population: OS 12.6 vs 9.7 mo (P=0.040) |
| Phase III | |||
| Rittmeyer et al4 and Fehrenbacher et al19 | Stage IIIB/IV NSCLC patients progressed to one line of platinum-based chemotherapy, regardless PD-L1 expression (850 pts for primary efficacy analysis; 1,225 pts for final analysis) | Atezolizumab 1,200 mg q3w or docetaxel 75 mg/m2 q3w | • Overall population: OS 13.3 vs 9.8 mo (P=0.0012); ORR 13.7% vs 11.8%; median DOR 23.9 vs 6.3 mo; PFS 2.7 vs 3.9 mo (P=0.498) |
| Socinski et al, IMpower150 trial24 | Stage IV or recurrent NSCLC patients with non- squamous histology, chemotherapy-naïve, regardless PD-L1 expression (1,202 pts) | Carboplatin AUC 6 and paclitaxel 200 mg/m2 q3w plus Arm A: atezolizumab 1,200 mg Arm B: bevacizumab 15 mg/kg Arm C: atezolizumab and bevacizumab |
Results regarding Arm C vs Arm B in WT patients • WT-overall population: PFS 8.3 vs 6.8 mo (P<0.001), ORR 63.5% vs 48%, DOR 9 vs 5.7 mo, OS 19.2 vs 14.7 mo • WT high Teff patients: PFS 11.3 vs 6.8 mo (P<0.001), ORR 69.3% vs 53.5%, DOR 11.2 vs 5.7 mo |
| Jotte et al, IMpower131 trial27 | Advanced NSCLC patients with squamous histology, chemotherapy naïve regardless PD-L expression (1,021 pts) | Arm A: atezolizumab, carboplatin, paclitaxel Arm B: atezolizumab, carboplatin, nab-paclitaxel Arm C: carboplatin, nab-paclitaxel |
Results regarding Arm B vs Arm C in WT patients • Overall population: PFS 6.3 vs 5.6 mo (P=0.0001), ORR 49% vs 40%, OS 14 vs 13.9 (P=0.693) |
Abbreviations: BID, bis in die (twice daily); DOR, duration of response; m, median; mo, months; NSCLC, non-small-cell lung cancer; ORR, overall response rate; OS, overall survival; PD-L1, programed death ligand-1; pts, patients; Teff, T-effector gene signature; PFS, progression-free survival; WT, wild-type; q3w, every three weeks.