Table 1.
A brief update on various approvals granted by FDA for immune checkpoint inhibitors linked to PD-L1 detection in the past 3 years.
| Trial | Tumor type | Drug | Year of approval | Line of therapy | PD-L1 threshold | Companion diagnostic | Number of patients | Endpoint | Results |
|---|---|---|---|---|---|---|---|---|---|
| KEYNOTE-355 | TNBC | Pembrolizumab + chemotherapy VS Placebo + chemotherapy | 2020 | 1st | CPSc ≥ 10 | IHC 22C3 | 566 | PFS, OS | Median PFS: 9.7 vs. 5.6 m |
| IMpower110 | adult patients with NSCLC | Atezolizumab VS Platinum-based chemotherapy | 2020 | 1st | TC ≥ 50% or IC ≥ 10% | SP142 | 277 | OS | Median OS: 20.2 vs 13.1 m Median PFS: 8.1 vs. 5.0 m |
| CHECKMATE-227 (Part 1a) | NSCLC | Nivolumab+ ipilimumab VS Platinum-doublet chemotherapy | 2020 | 1st | TC ≥ 1% | IHC 28-8 | 396 | OS | Median OS: 17.1 vs. 14.9 m |
| KEYNOTE-181 | ESCCa | Pembrolizumab VS Chemotherapy | 2019 | 2nd | CPS ≥10 | IHC 22C3 | 85 | OS | Median OS: 10.3 vs. 6.7 m |
| KEYNOTE-180 | Pembrolizumab | 3rd | 121 | ORR, response duration | ORR: 20% | ||||
| KEYNOTE-042 | NSCLC | Pembrolizumab V.S Carboplatin-containing chemotherapy | 2019 | 1st | TPSd ≥ 1% | IHC 22C3 | 637 | OS | Median OS: TPS ≥ 1%: 16.7 vs. 12.1 m TPS ≥ 20%: 17.7 vs. 13.0 m TPS ≥ 50%: 20 vs. 12.2 m |
| IMpassion130 | TNBC | Atezolizumab + nab-paclitaxel VS Placebo + nab-paclitaxel | 2019 | 1st | IC ≥ 1% | SP142 | 451 | PFS, OS | Median OS: 7.4 vs. 4.8 m |
| KEYNOTE-048 subgroups | HNSCC | Pembrolizumab VS Cetuximab plus chemotherapy | 2019 | CPS ≥ 1 | IHC 22C3 | 301 | OS | Median OS: CPS ≥1: 12.3 vs. 10.3 m CPS ≥ 20: 14.9 vs. 10.7 m | |
| KEYNOTE-158 | Cervical cancer | Pembrolizumab | 2018 | 2nd | CPS ≥ 1 | IHC 22C3 | 98 | ORR | ORR:14.3%b |
| KEYNOTE-059 | Gastric/GEJ | Pembrolizumab | 2017 | 3rd | CPS ≥ 1 | IHC 22C3 | 259 | ORR | Overall ORR: 11.6% PD-L1+:15.5% PD-L1-: 6.4% |
| NCT01693562 | Urothelial carcinoma | Durvalumab | 2017 | 2nd | TC or IC≥ 25% | SP263 | 191 | ORR | Overall ORR: 17.8% PD-L1+:27.6% PD-L1-: 5.1% |
Efficacy of pembrolizumab was investigated in two clinical trials, KEYNOTE-181 and KEYNOTE-180.
ORR was 14.3% with a median follow-up time of 11.7 months in 77 patients with PD-L1–positive tumors. No responses were observed in patients whose tumors did not have PD-L1 expression.
TPS is calculated as the ratio between the number of PD-L1+ tumor cells and the total number of tumor cells.
CPS is calculated as the ratio between the number of all PD-L1+ cells and the total number of cells.
TNBC, triple-negative breast cancer; CPS, combined positive score; NSCLC, non-small cell lung cancer; GEJ, gastroesophageal junction; IC, immune cells; TC, tumor cells; TPS, tumor proportion score; HNSCC, head and neck squamous cell carcinoma; ESCC, squamous cell carcinoma of the esophagus.