Table 1 Clinical trials of PD-1/PD-L1 inhibitors
From: Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors
Agents | Tumors | PD-L1 IHC platforms | Cells scored by IHC | Cutoff | Efficacy of agent | Clinical trial | Ref. |
|---|---|---|---|---|---|---|---|
Pembrolizumab | Urothelial cancer | Dako 22C3 pharmDx Assay | Combined score of TC and IC | < 1%: | 11, 95%CI 4–24% (ORRa) | Keynote-052 | [30] |
1–9% | 20, 95%CI 14–28%(ORRa) | ||||||
≥10% | 39, 95% CI 28–50% (ORRa) | ||||||
Melanoma | Dako 22C3 pharmDx Assay | Combined score of TC and IC | < 1%: | 36.4, 95% CI 10.9–69.2% (ORRb) | Keynote-041 | [116] | |
≥1% | 16.7%, 95% CI 3.6–41.4% (ORRb) | ||||||
HNSCC | Dako 22C3 pharmDx Assay | Combined score of TC and IC | < 50%: | 13, 95%CI 7–20% (ORRb) | Keynote-055 | [117] | |
≥50% | 27, 95%CI 15–42% (ORRb) | ||||||
NSCLC | Dako 22C3 pharmDx Assay | TC | < 1% | 8.3, 95% CI 0.2–38.5%(ORRa) | Keynote-001 | [118] | |
1–49% | 17.3, 95% CI 8.2–30.3% (ORRa) | ||||||
≥50% | 51.9, 95% CI 31.9–71.3% (ORRa) | ||||||
Melanoma | Dako 22C3 pharmDx Assay | Combined score of TC and IC | < 1% | 2.8moths, 95% CI 2.7–2.8 months (PFS) 12.6 months, 95% CI 7.0–18.5 months (OS) | Keynote-001 | [119] | |
≥1% | 5.6 months, 95% CI 4.4–8.1 months (PFS) 29.9 months, 95% CI 24.6-NR months (OS) | ||||||
Nivolumab | Squamous NSCLC | Dako 28–8 pharmDx Assay | TC | < 1% | HR of 2 years OS between Nivolumab and Docetaxel HR:0.57, 95%CI 0.38–0.86 | Checkmate-017 | [120] |
≥1% | HR:0.75, 95%CI 0.50–1.10 | ||||||
≥5% | HR:0.57, 95%CI 0.36–0.92 | ||||||
≥10% | HR:0.56, 95%CI 0.33–0.94 | ||||||
≥50% | HR:0.63, 95%CI 0.25–1.57 | ||||||
Non-squamous NSCLC | Dako 28–8 pharmDx Assay | TC | < 1% | HR of 2 years OS between Nivolumab and Docetaxel HR:0.91, 95%CI 0.67–1.22 | Checkmate-057 | [120] | |
≥1% | HR:0.62, 95%CI 0.47–0.83 | ||||||
≥5% | HR:0.48, 95%CI 0.34–0.68 | ||||||
≥10% | HR:0.43, 95%CI 0.30–0.62 | ||||||
≥50% | HR:0.38, 95%CI 0.24–0.60 | ||||||
Urothelial cancer | Dako 28–8 pharmDx Assay | TC | < 1% | 16.1, 95% CI 10.5–23.1% (ORRa) | Checkmate-275 | [121] | |
≥1% | 23.8, 95% CI 16.5–32.3% (ORRa) | ||||||
≥5% | 28.4, 95% CI 18.9–39.5% (ORRa) | ||||||
Urothelial cancer | Dako 28–8 pharmDx Assay | TC | < 1% | 26.2%; 95% CI 13.9–42.0%(ORRa)9·9 months, 95% CI 7.0–not estimable (median OS) | Checkmate-032 | [31] | |
≥1% | 24.0%; 95% CI 9.4–45.1% (ORRa)16.2 months, 95% CI 7.6–NE (median OS) | ||||||
Renal cell cancer | Dako Assayc | TC | < 1% | HR of median OS between Nivolumab and everolimusHR: 0.76; 95% CI 0.60–0.97 | Checkmate-025 | [122] | |
≥1% | HR: 0.78; 95% CI 0.53–1.16 | ||||||
Squamous NSCLC | Dako Assayc | TC | < 5% | Best overall response 14% (PR),20% (SD),49% (PD) | Checkmate-063 | [123] | |
≥5% | Best overall response 24% (PR),24% (SD),44% (PD) | ||||||
Renal cell cancer | Dako 28–8 pharmDx Assay | TC | < 5% | 18% (ORRa)2.9 months (median PFS) | NCT01354431. | [124] | |
≥5% | 31% (ORRa)4.9 months (median PFS) | ||||||
Melanoma | Dako Assayc | TC | < 5% or undefined | ORRa: 33.1, 95% CI 25.2–41.7% vs. 15.7%, 95% CI 10.0–23.0% (nivolumab vs. dacarbazine) | Checkmate-066 | [125] | |
≥5% | ORRa: 52.7, 95% CI 40.8–64.3% vs. 10.8%, 95% CI 4.8–20.2% (nivolumab vs. dacarbazine) | ||||||
Multiple cancers | IHC staining with anti-PD-L1 mAb 5H1 | TC | < 5% | 0% (ORRa) | NCT00730639 | [126] | |
≥5% | 36% (ORRa) | ||||||
Atezolizumab | NSCLC | Ventana SP142 assay | TC or IC | TC and IC < 1% | HR of OS between atezolizumab and docetaxel HR:0.75, 95% CI 0.59–0.96 | OAK | [127] |
TC or IC ≥ 1% | HR:0.74, 95% CI 0.58–0.93 | ||||||
Urothelial cancer | Ventana SP142 assay | IC | < 1% | 21, 95%CI 9–37% (ORRa) | NCT02108652 | [128] | |
1–4% | 21, 95%CI 11–35%(ORRa) | ||||||
≥5% | 28, 95%CI 14–47% (ORRa) | ||||||
Renal cell cancer | Ventana SP142 assay | IC | < 1% | 9, 95%CI 1–29% (ORRa)51, 95%CI 27–74% (2-Years OS Rate) | NCT01375842 | [129] | |
≥1% | 18, 95%CI7–35% (ORRa)65, 95%CI45–86% (2-Years OS Rate) | ||||||
Multiple cancers | Ventana SP142 assay | IC | < 1% | 13%(ORRa), 24-weeks PFS:33.9% | NCT01375842 | [130] | |
1–4% | 21% (ORRa), 24-weeks PFS:40.9% | ||||||
5–9% | 17% (ORRa), 24-weeks PFS:43.0% | ||||||
≥10% | 46% (ORRa), 24-weeks PFS:60.0% | ||||||
NSCLC | Ventana SP142 assay | TC or IC | TC and IC < 1% | HR of OS between atezolizumab and docetaxel:1.04, 95%CI 0.62–1.75 | POPLAR | [131] | |
TC or IC ≥1% | HR of OS between atezolizumab and docetaxel: 0.59, 95%CI 0.40–0.85 | ||||||
TC or IC ≥5% | HR of OS between atezolizumab and docetaxel: 0.54, 95%CI 0.33–0.89 | ||||||
TC ≥50% or IC ≥10% | HR of OS between atezolizumab and docetaxel: 0.49, 95%CI 0.22–1.07 | ||||||
Durvalumab | Urothelial cancer | Ventana SP263 assay | TC or IC | TC and IC < 25% | 5.1, 95%CI 1.4–12.5%(ORRa) | NCT01693562 | [132] |
TC or IC ≥25% | 27.6,95%CI 19.0–37.5%(ORRa) | ||||||
Avelumab | Urothelial cancer | Dako assay | TC | < 5% | 4.2% (ORRb)12 months-OS rate: 56.3, 95%CI 33.7–73.9% | NCT01772004 | [133] |
≥5% | 53.8% (ORRb)12 months-OS rate: 75.5, 95%CI 41.6–91.4% |