Table 2 Effect of PD-L1 cut-off on outcome in phase 3 trials of PD-1 pathway inhibitors.

 IMpower 131 [82]

SP142

Atezolizumab + carboplatin + nab-paclitaxel vs carboplatin + nab-paclitaxel

ITT: 14.2 vs 13.5 (0.88, 0.73–1.05)

TC3 or IC3: 23.4 vs 10.2 (0.48, 0.29–0.81)^a

ITT: 6.3 vs 5.6 (0.71, 0.60–0.85)^a

TC3 or IC3: 10.1 vs 5.1 (0.41, 0.25–0.68)^a

 IMpower150 [83]

SP142

Atezolizumab + carboplatin + paclitaxel vs bevacizumab + carboplatin + paclitaxel

ITT: 19.0 vs 14.7 (0.84, 0.71–1.00)

TC3 or IC3: 26.3 vs 15.0 (0.76, 0.49–1.17)

TC1/2/3 or IC1/2/3: 24.4 vs 16.0 (0.71, 0.55–0.91)^a

TC0 and IC0: 14.8 vs 14.1 (0.96, 0.76–1.22)

ITT: 6.3 vs 6.8 (0.82, 0.70–0.97)^a

TC3 or IC3: 8.3 vs 6.8 (0.57, 0.39–0.83)^a

TC1/2/3 or IC1/2/3: 7.1 vs 6.8 (0.67, 0.53–0.83)^a

TC0 and IC0: 5.4 vs 6.9 (0.98, 0.78–1.23)

Atezolizumab + bevacizumab + carboplatin + paclitaxel vs bevacizumab + carboplatin + paclitaxel

ITT: 19.5 vs 14.7 (0.80, 0.67–0.95)^a

TC3 or IC3: 30.0 vs 15.0 (0.70, 0.46–1.08)

TC1/2/3 or IC1/2/3: 22.5 vs 16.0 (0.73, 0.57–0.94)^a

TC0 and IC0: 16.9 vs 14.1 (0.90, 0.71–1.14)

ITT: 8.4 vs 6.8 (0.57, 0.48–0.67)^a

TC3 or IC3: 15.2 vs 6.8 (0.34, 0.23–0.50)^a

TC1/2/3 or IC1/2/3: 11.1 vs 6.8 (0.47, 0.38–0.60)^a

TC0 and IC0: 7.2 vs 6.9 (0.71, 0.57–0.89)^a

 KEYNOTE-189 [84]

22C3

Pembrolizumab + pemetrexed-platinum vs placebo + pemetrexed-platinum

ITT: 22.0 vs 10.7 (0.56, 0.45–0.70)^a

TPS ≥ 50%: not reached vs 10.1 (0.59, 0.39–0.88)^a

TPS 1-49%: 21.8 vs 12.1 (0.62, 0.42–0.92)^a

TPS < 1%: 17.2 vs 10.2 (0.52, 0.36–0.74)^a

ITT: 9.0 vs 4.9 (0.48, 0.40–0.58)^a

TPS ≥ 50%: 11.1 vs 4.8 (0.36, 0.26–0.51)^a

TPS 1%–49%: 9.2 vs 4.9 (0.51, 0.36–0.73)^a

TPS < 1%: 6.2 vs 5.1 (0.64, 0.47–0.89)^a

 IMpower133 [85]

SP263

Atezolizumab + carboplatin + etoposide vs placebo + carboplatin + etoposide

ITT: 12.3 vs 10.3 (0.76, 0.60–0.95)^a

≥5% TC or IC: 21.6 vs 9.2 (0.60, 0.25–1.46)

<5% TC or IC: 9.2 vs 8.9 (0.77, 0.51–1.17)

≥1% TC or IC: 9.7 vs 10.6 (0.87, 0.51–1.49)

<1% TC and IC: 10.2 vs 8.3 (0.51, 0.30–0.89)^a

ITT: 5.2 vs 4.3 (0.77, 0.62–0.96)^a

≥1% TC or IC: 5.1 vs 5.5 (0.86, 0.51–1.46)

<1% TC or IC: 5.4 vs 4.2 (0.52, 0.31–0.88)^a

 IMpower132 [86]

SP142

Atezolizumab + carboplatin or cisplatin + pemetrexed vs carboplatin or cisplatin + permetrexed

ITT: 17.5 vs 13.6 (0.86, 0.71–1.06)

TC3 or IC3: not reached vs 26.9 (0.73, 0.31–1.73)

TC1/2 or IC1/2: 12.7 vs 16.2 (1.18, 0.80–1.76)

TC0 and IC0: 15.9 vs 10.5 (0.67, 0.46–0.96)^a

ITT: 7.7 vs 5.2 (0.56, 0.47–0.67)^a

TC3 or IC3: 10.8 vs 6.5 (0.46, 0.22–0.96)^a

TC1/2 or IC1/2: 6.2 vs 5.7 (0.80, 0.56–1.16)

TC0 and IC0: 8.5 vs 4.9 (0.45, 0.31–0.64)^a

 IMpower110 [87]

SP142

Atezolizumab vs chemotherapy

TC3 or IC3: 20.2 vs 13.1 (0.59, 0.40–0.89)^a

TC2/3 or IC2/3: 18.2 vs 14.9 (0.72, 0.52–0.99)^a

TC1/2/3 or IC1/2/3: 17.5 vs 14.1 (0.83, 0.65–1.07)

TC3 or IC3: 8.1 vs 5.0 (0.63, 0.45–0.88)^a

TC2/3 or IC2/3: 7.2 vs 5.5 (0.67, 0.52–0.88)^a

TC1/2/3 or IC1/2/3: 5.7 vs 5.5 (0.77, 0.63–0.94)^a

 IMpower130 [88]

SP142

Atezolizumab + carboplatin + nab-paclitaxel vs carboplatin + nab-paclitaxel

ITT: 18.6 vs 13.9 (0.79, 0.64–0.98)^a

TC3 or IC3: 17.3 vs 16.9 (0.84, 0.51–1.39)

TC1/2 or IC1/2: 23.7 vs 15.9 (0.70, 0.45–1.08)

TC0 and IC0: 15.2 vs 12.0 (0.81, 0.61–1.08)

ITT: 7.0 vs 5.5 (0.64, 0.54–0.77)^a

TC3 or IC3: 6.4 vs 4.6 (0.51, 0.34–0.77)^a

TC1/2 or IC1/2: 8.3 vs 6.0 (0.61, 0.43–0.85)^a

TC0 and IC0: 6.2 vs 4.7 (0.72, 0.56–0.91)^a

 KEYNOTE-010 [89]

22C3

Pembrolizumab 2 mg/kg vs docetaxel

ITT: 10.4 vs 8.5 (0.71, 0.58–0.88)^a

≥50% TC: 14.9 vs 8.2 (0.54, 0.38–0.77)^a

ITT: 3.9 vs 4.0 (0.88, 0.74–1.05)

≥50% TC: 5.0 vs 4.1 (0.59, 0.44–0.78)^a

Pembrolizumab 10 mg/kg vs docetaxel

ITT: 12.7 vs 8.5 (0.61, 0.49–0.75)^a

≥50% TC: 17.3 vs 8.2 (0.50, 0.36–0.70)^a

ITT: 4.0 vs 4.0 (0.79, 0.66–0.94)^a

≥50% TC: 5.2 vs 4.1 (0.59, 0.45–0.78)^a

 KEYNOTE-042 [90]

22C3

Pembrolizumab vs investigator’s choice of platinum-based chemotherapy

TPS ≥ 50%: 20.0 vs 12.2 (0.69, 0.56–0.85)^a

TPS ≥ 20%: 17.7 vs 13.0 (0.77, 0.64–0.92)^a

TPS ≥ 1%: 16.7 vs 12.1 (0.81, 0.71–0.93)^a

TPS ≥ 50%: 7.1 vs 6.4 (0.81, 0.67–0.99)^a

TPS ≥ 20%: 6.2 vs 6.6 (0.94, 0.80–1.11)

TPS ≥ 1%: 5.4 vs 6.5 (1.07, 0.94–1.21)

 KEYNOTE-407 [91]

22C3

Pembrolizumab + carboplatin + paclitaxel or nab-paclitaxel vs placebo + carboplatin + paclitaxel or nab-paclitaxel

ITT: 15.9 vs 11.3 (0.64, 0.49–0.85)^a

TPS ≥ 50%: not reached in either arm (0.64, 0.37–1.10)

TPS 1–49%: 14.0 vs 11.6 (0.57, 0.36–0.90)^a

TPS < 1%: 15.9 vs 10.2 (0.61, 0.38–0.98)^a

ITT: 6.4 vs 4.8 (0.56, 0.45–0.70)^a

TPS ≥ 50%: 8.0 vs 4.2 (0.37, 0.24–0.58)^a

TPS 1–49%: 7.2 vs 5.2 months (0.56, 0.39–0.80)^a

TPS < 1%: 6.3 vs 5.3 (0.68, 0.47–0.98)^a

 OAK [92]

SP142

Atezolizumab vs docetaxel

ITT: 13.8 vs 9.6 (0.73, 0.62–0.87)^a

TC3 or IC3: 20.5 vs 8.9 (0.41, 0.27–0.64)^a

TC2/3 or IC2/3: 16.3 vs 10.8 (0.67, 0.49–0.90)^a

TC1/2/3 or IC1/2/3: 15.7 vs 10.3 (0.74, 0.58–0.93)^a

TC0 and IC0: 12.6 vs 8.9 (0.75, 0.59–0.96)^a

ITT: 2.8 vs 4.0 (0.95, 0.82–1.10)

TC3 or IC3: 4.2 vs 3.3 (0.63, 0.43–0.91)^a

TC2/3 or IC2/3: 4.1 vs 3.6 (0.76, 0.58–0.99)^a

TC1/2/3 or IC1/2/3: 2.8 vs 4.1 (0.91, 0.74–1.12)

TC0 and IC0: 2.6 vs 4.0 (1.00, 0.80–1.25)

 ONO-4538-52/TASUKI-52 [93]

28-8

Nivolumab + carboplatin + paclitaxel + bevacizumab vs placebo + carboplatin + paclitaxel + bevacizumab

ITT: 25.4 vs 24.7 (0.85, 0.63–1.14)

ITT: 12.1 vs 8.1 (0.56, 0.43–0.71)^a

≥50% TC: 9.9 vs 6.9 (0.55, 0.36–0.83)^a

1–49% TC: 11.0 vs 8.4 (0.63, 0.42–0.96)^a

<1% TC or indeterminate: 13.6 vs 8.4 (0.55, 0.38–0.78)^a

 CheckMate 238 [94]

28-8

Nivolumab vs ipilimumab

4-year recurrence-free survival rate

ITT: 51.7 vs 41.2 (0.71, 0.60–0.86)^a

≥5% TC: 64.0% vs 52.3% (0.67, 0.47–0.96)^a

<5% TC: 44.2% vs 35.7% (0.75, 0.60–0.93)^a

≥1% TC: 56.4% vs 45.2% (0.68, 0.54–0.86)^a

<1% TC: 40.6% vs 33.2% (0.79, 0.58–1.08)

 JAVELIN Bladder 100 [95]

SP263

Avelumab + best supportive care vs best supportive care

ITT: 21.4 vs 14.3 (0.69, 0.56–0.86)^a

PD-L1 positive (≥25% TC, or ≥25% IC if >1% tumour area contains IC, or 100% IC if <1% tumour area contains IC): not reached vs 17.1 (0.56, 0.40–0.79)^a

PD-L1 negative (criteria for PD-L1 positivity not met): 18.8 vs 13.7 (0.85, 0.62–1.18)

ITT: 3.7 vs 2.0 (0.62, 0.52–0.75)^a

PD-L1 positive: 5.7 vs 2.1 (0.56, 0.43–0.73)^a

PD-L1 negative: 3.0 vs 1.9 (0.63, 0.47–0.85)^a

 IMvigor010 [96]

SP142

Atezolizumab vs observation

Median disease-free survival

ITT: 19.4 vs 16.6 (0.89, 0.74–1.08)

IC0/1: 16.4 vs 11.1 (0.85, 0.66–1.10)

IC2/3: 24.8 vs 41.4 (1.01, 0.76–1.35)

 CheckMate 274 [97]

28-8

Nivolumab vs placebo

6-month disease-free survival

ITT: 74.9% vs 60.3% (0.70, 0.55–0.90)^a

≥1% TC: 74.5% vs 55.7% (0.55, 0.35–0.85)^a

6-month recurrence-free survival

ITT: 77.0% vs 62.7% (0.72, 0.59–0.89)^a

≥1% TC: 75.3% vs 56.7% (0.55, 0.39–0.79)^a

 KEYNOTE-361 [98]

22C3

Pembrolizumab vs gemcitabine + investigator’s choice of cisplatin or carboplatin

ITT: 15.6 vs 14.3 (0.92, 0.77–1.11)

CPS ≥ 10: 16.1 vs 15.2 (1.01, 0.77–1.32)