Table 2. . Chemo-immunotherapy in advanced non-small-cell lung cancer patients in frontline setting.
| Trial | Patient (n) | PD-L1 IHC | Agent | Primary end point (months) | Outcome by PD-L1 (months or HR) | Outcome by TMB (months) | US FDA approval |
|---|---|---|---|---|---|---|---|
| Chemo IO | |||||||
| KEYNOTE-189 (NCT02578680) |
n = 616, nonsquamous | PD-L1 by 22C3 by Agilent | Pemetrexed-platinum + pembrolizumab vs pemetrexed-platinum + placebo | OS: not reached vs 11.3 (95% CI: 8.7–15) PFS: 8.8 (95% CI: 7.6–9.2) vs 4.9 (95% CI: 4.7–5.5) |
OS: <1%: HR: 0.59 (95% CI: 0.38–0.92) ≥1–49%: HR: 0.55 (95% CI: 0.34–0.90) ≥50%: HR: 0.42 (95% CI: 0.26–0.68) |
OS: TMB ≥175: HR: 0.64 (95% CI: 0.38–1.07) TMB <175: 0.64 (95% CI: 0.42–0.97) |
August 2018 |
| KEYNOTE-407 (NCT02775435) |
n = 559, squamous |
PD-L1 by 22C3 by Agilent | Carboplatin + paclitaxel or nab-paclitaxel + pembrolizumab/placebo | OS: 15.9 (95% CI: 13.2, not reached) vs 11.3 (95% CI: 9.5–14.8) PFS: 6.4 (95% CI: 6.2–8.3) vs 4.8 (95% CI: 4.3–5.7) |
OS: <1%: HR: 0.61 (95% CI: 0.38–0.98) ≥1–49%: HR: 0.57 (95% CI: 0.36–0.9) ≥50%: HR: 0.64 (95% CI: 0.37–1.10) |
OS: TMB ≥175: HR: 0.74 (95% CI: 0.5–1.08) TMB <175: HR: 0.86 (95%: 0.57–1.28) |
October 2018 |
| IMpower-150 (NCT02366143) |
n = 1202 nonsquamous |
PD-L1 by SP142 by Ventana | ACP vs BCP vs ABCP | PFS: 8.3 ABCP vs 6.8 BCP, HR: 0.62 (95% CI: 0.52–0.74) OS: 19.2 ABCP vs 14.7 BCP, HR: 0.78 (95% CI: 0.64–0.96) |
PFS: TC3 or IC3: HR: 0.39 (95% CI: 0.25–0.60) TC 1/2/3 or IC 1/2/3: HR: 0.50 (95% CI: 0.39–0.64) TC0 and IC0: HR: 0.77 (95% CI: 0.61–0.99) |
NA | December 2018 |
| IMpower-130 (NCT02367781) |
n = 724 nonsquamous |
PD-L1 by VENTANA SP142 assay | Atezolizumab + carboplatin + nab-paclitaxel followed by atezolizumab vs carboplatin + nab-paclitaxel followed by pemetrexed | PFS: 7.0 vs 5.5, HR: 0.64 (95% CI: 0.54–0.77) OS: 18.6 vs 13.9, HR: 0.79 (95% CI: 0.64–0.98) |
OS: PD-L1 high: 17.3 vs 16.9, HR: 0.84 (95% CI: 0.51–1.39) PD-L1 low: 23.7 vs 15.9, HR: 0.70 (95% CI: 0.45–1.08) PD-L1 neg: 15.2 vs 12.0, HR: 0.81 (95%: 0.61–1.08) PFS: PD-L1 high: 6.4 vs 4.6, HR: 0.51 (0.34–0.77) PD-L1 low: 8.3 vs 6.0, HR: 0.61 (0.43–0.85) PD-L1 neg: 6.2 vs 4.7, HR: 0.72 (0.56–0.91) |
NA | December 2019 |
TC3 or IC3: PD-L1 ≥50% or ≥10% tumor-infiltrating immune cell; TC 1/2/3 or IC 1/2/3: PD-L1 expression ≥1% of tumor cell or tumor-infiltrating immune cell; TC0 and IC0: PD-L1 expression <1% of tumor cell and tumor-infiltrating immune cell.
ABCP: Atezolizumab/bevacizumab/carboplatin/paclitaxel; ACP: Aztezolizumab/carboplatin/paclitaxel; BCP: Bevacizumab/carboplatin/paclitaxel; HR: Hazard ratio; IO: Immunotherapy; NA: Not available; OS: Overall survival; PFS: Progression-free survival; TMB: Tumor mutational burden.