TABLE 1.
Main studies of tumor PD‐L1 expression to predict immunotherapy in the last 5 years.
| Cancer type | Study design | Number of patients | Assay | Therapy | Key findings | References |
|---|---|---|---|---|---|---|
| Dependent of PD‐L1 expression | ||||||
| Treated/untreated NSCLC | KEYNOYE‐001, phase 1 | 550 | IHC, 22C3 | Pembrolizumab | PD‐L1 TPS ≥ 50% was associated with longer mOS vs. TPS 1−49% | Leighl et al. 5 |
| Untreated NSCLC | KEYNOTE‐042, phase 3 | 1274 | IHC, 22C3 | Pembrolizumab/platinum‐based chemotherapy | OS was better for pembrolizumab than chemotherapy in all PD‐L1 TPS groups (≥50, ≥20, and ≥1%). | Mok et al. 6 |
| Treated melanoma | KEYNOTE‐151, phase 1b | 103 | IHC, 22C3 | Pembrolizumab | Median OS was associated with PD‐L1‐positive (1 vs. <1%). | Si et al. 9 |
| 20 solid tumora | KEYNOTE‐028, phase Ib | 475 | IHC, 22C3 | Pembrolizumab | PD‐L1 CPS > 1% and TMB were correlated with higher ORR and PFS. | Ott et al. 21 |
| Treated NSCLC | KEYNOTE‐033, phase 3 | 425 | IHC, 22C3 | Pembrolizumab/docetaxel‐based chemotherapy | Longer OS was associated with increasing PD‐L1 TPS ≥ 1%. | Ren et al. 22 |
| Untreated NSCLC | KEYNOTE‐024, phase 3 | 305 | IHC, 22C3 | Pembrolizumab/platinum‐based chemotherapy | PD‐L1 TPS ≥ 50% was associated with superior OS and mPFS for pembrolizumab. | Reck et al. 23 |
| Treated NSCLC | POPLAR, phase 2, OAK phase 3 | 287, 1225 | IHC, 22C3 | Atezolizumab/docetaxel‐based chemotherapy | Longer OS was associated with increasing PD‐L1 TPS ≥ 1%. | Mazieres et al. 24 |
| Independent of PD‐L1 expression | ||||||
| Untreated nonsquamous NSCLC | KEYNOTE‐189, phase 3 | 410 | IHC, 22C3 | Pembrolizumab+pemetrexed/platinum‐based chemotherapy | OS, PFS, and ORR benefit was better in pembrolizumab + pemetrexed vs. chemotherapy group, regardless of PD‐L1 (TPS 1 vs. < 1%). | Rodriguez‐Abreu et al. 7 |
| Untreated HCC | KEYNOTE‐224, Phase 2 | 51 | N/A | Pembrolizumab | Durable responses were observed in PD‐L1+ expression (<1 vs. ≥1%) | Verset et al. 11 |
| Untreated NSCLC | CheckMate 227, 817, 568, and 012 | 1332 | IHC, 28‐8 | Nivolumab + ipilimumab | Durable survival benefit with nivolumab + ipilimumab were revealed regardless of tumor PD‐L1 (<1 vs. ≥1%) and histology. | Borghaei et al. 12 |
| Treated NSCLC | CheckMate 017, 057, phase 3 | 272, 582 | IHC, 28‐8 | Nivolumab/platinum‐based chemotherapy | Durable responses were observed with nivolumab independent of histology and PD‐L1 TPS (≥1, ≥5, and ≥10%). | Borghaei et al. 26 |
| Untreated PD‐L1(‐) NSCLC | KEYNOTE‐021, 189, 407 | 1328 | IHC, 22C3 | Pembrolizumab+chemotherapy/chemotherapy | Pembrolizumab plus chemotherapy improved OS and PFS over chemotherapy (PD‐L1 TPS < 1%). | Borghaei et al. 27 |
| HCC | GO30140, phase 1b | 223 | IHC, SP263 | Atezolizumab with or without bevacizumab | PFS benefit was observed in atezolizumab plus bevacizumab irrespective of PD‐L1 status (three different cutoff TPS ≥ 1, ≥5, and ≥10%). | Lee et al. 28 |
| Untreated NSCLC | CheckMate 227 | 1739 | IHC, 28‐8 | Nivolumab + ipilimumab/nivolumab/chemotherapy | Nivolumab plus ipilimumab increased 5‐year OS and DCB vs. chemotherapy, regardless of PD‐L1 expression (<1 vs. ≥1%). | Brahmer et al. 29 |
| Untreated NSCLC | CheckMate 9LA, phase 3 | 719 | IHC, 28‐8 | Nivolumab plus ipilimumab/chemotherapy | OS, PFS, and ORR was greater in nivolumab plus ipilimumab vs. chemotherapy, regardless of PD‐L1 TPS and histology (<1 vs. ≥1%). | Paz‐Ares et al. 30 |
ICIs, Immune checkpoint inhibitors; PD‐1, programmed cell death protein‐1; PD‐L1, programmed cell death‐ligand 1; CTLA‐4, cytotoxic T‐lymphocyte antigen‐4; NSCLC, non‐small cell lung cancer; mOS, median overall survival; HCC, hepatocellular carcinoma; PFS, progression‐free survival; TPS, tumor cell proportion score; CPS, combined positive score; IHC, immunohistochemistry; SP263, VENTANA PD‐L1; DCB, durable clinical benefit; ORR, objective response rate.
a20 solid tumor: anal canal squamous cell carcinoma, biliary tract adenocarcinoma, breast cancer, carcinoid tumors, cervical squamous cell carcinoma colon/rectal adenocarcinoma, endometrial, esophageal carcinoma, glioblastoma multiforme, leiomyosarcoma, mesothelioma, nasopharyngeal, neuroendocrine, ovarian epithelial cancer, pancreatic adenocarcinoma, prostate adenocarcinoma, salivary gland, small‐cell lung carcinoma, thyroid cancer, vulvar small‐cell lung carcinoma.