Table 1 Clinical trials on immune checkpoint inhibitors in non–small cell lung cancer

CheckMate 017

III

SqNSCLC/ second

Nivolumab at 3 mg/kg vs. docetaxel at 75 mg/m²

Significant improvement in OS for patients receiving nivolumab compared with docetaxel (median, 9.2 vs. 6.0 mo; HR, 0.59; p < .001).

Response rate was 20% with nivolumab vs. 9% with docetaxel (P = 0.008)

PD-L1 expression was neither prognostic nor predictive for efficacy end points

CheckMate 057

III

Non-SqNSCLC/second

Nivolumab at 3 mg/kg vs. docetaxel at 75 mg/m²

Significant improvement in OS for patients receiving nivolumab compared with docetaxel (median 12.2 vs. 9.4 mo; HR, 0.73; p = .002).

Response rate was 19% with nivolumab vs. 12% with docetaxel (P = 0.02)

PD-L1 expression was associated with even greater efficacy at all expression levels (≥1%, ≥5%, and ≥ 10%).

KEYNOTE 010

II/III

NSCLC PD-L1-positive tumors (PS ≥ 1%)/second

Pembrolizumab at 2 mg/kg or 10 mg/kg vs. docetaxel 75 mg/m²

Significant improvement in OS for pembrolizumab at 2 mg/kg (median 10.4 vs. 8.5 mo; HR, 0.71; p = .0008) and pembrolizumab at 10 mg/kg (median, 12.7 vs. 8.5 mo; HR, 0.61; p < .001) compared with docetaxel

Response rate was 18% with pembrolizumab (2 mg and 10 mg vs. 9% with docetaxel (P = 0.0005 and 0.0002)

Pembrolizumab efficacy was greater in patients with tumor PS ≥50%

KEYNOTE 024

III

NSCLC, PD-L1-positive tumors (PS ≥50%), no sensitizing mutation of EGFR or translocation of ALK/first

Pembrolizumab at fixed dose of 200 mg or platinum-based chemotherapy

Significant improvement in PFS for patients receiving pembrolizumab compared with chemotherapy (median 10.3 vs. 6.0 mo; HR, 0.5; p < .00001).

Response rate was 44.8% with pembrolizumab vs. 27.8% with chemotherapy

All patients, PD-L1 expression on at least 50% of tumor cells

POPLAR

II

NSCLC/ second

Atezolizumab 1200 mg vs. docetaxel 75 mg/m²

Significant improvement in OS for patients receiving atezolizumab compared with docetaxel (median, 12.6 vs. 9.7 mo; HR, 0.73; P = .04)

Objective responses with atezolizumab were durable, with a median duration of 14·3 months (95% CI 11·6–non-estimable) compared with 7·2 months (5·6–12·5) for docetaxel

As with OS, PFS and ORR tended to show increased atezolizumab benefit with increasing PD-L1 expression.

OAK

III

NSCLC/ second

Atezolizumab at 1200 mg vs. docetaxelat 75 mg/m²

Significant improvement in OS for patients receiving atezolizumab compared with docetaxel (median 13.8 vs. 9.6 mo; HR, 0.73; P = .0003).

For ITT population, response rate was 14% with atezolizumab vs. 13% with docetaxel

Overall survival was improved regardless of PD-L1 expression levels. Patients with tumors expressing high levels of PD-L1 (TC3 or IC3) derived the greatest benefit from atezolizumab

PACIFIC

III

Stage III NSCLC with no disease progression after ≥2 cycles of chemoradiotherapy/second

Durvalumab at 10 mg/kg vs. placebo

Significant improvement in PFS and OS for patients with durvalumab vs. with placebo (PFS median 17.2 vs. 5.6 mo; HR, 0.51, P < 0.001; HR for OS =0.68, P = 0,0025);

Response rate was 28% with durvalumab vs. 16% with placebo

PFS and OS benefits with durvalumab were observed in all subgroups, including PD-L1 expression ≥25% or < 25%