Table 1.
Selected clinical studies on immune checkpoint inhibitors, which evaluated associations between clinical outcomes and the level of PD-L1 expression analysis.
| References | Brief description of the study | Survival | Predictive role of PD-L1 |
|---|---|---|---|
| Pembrolizumab (IHC: 22C3) | |||
| Herbst et al. (8) (KEYNOTE-010) | Assessment of long-term outcomes of pembrolizumab vs. docetaxel monotherapy in previously treated NSCLC with PD-L1 expression in >/=1% tumor cells | OS PD-L1 1-49%: pembrolizumab: 11.8 months; docetaxel: 8.4 months PD-L1 >/=50%: pembrolizumab: 16.9 months; docetaxel: 8.2 months |
Dramatic improvement of OS for pembrolizumab in patients with PD-L1 expression in >/=50% tumor cells; moderate improvement of OS in patients with PD-L1 expression score 1–49% |
| Gadgeel et al. (9) (KEYNOTE-189) | First-line therapy, non-squamous NSCLC: pembrolizumab or placebo plus pemetrexed and platinum | OS PD-L1 <1%: pembrolizumab plus chemotherapy: 17.2 months; pembrolizumab plus placebo: 10.2 months PD-L1 1-49%: pembrolizumab plus chemotherapy: 21.8 months; pembrolizumab plus placebo: 12.1 months PD-L1 >/=50%: pembrolizumab plus chemotherapy: not reached; pembrolizumab plus placebo: 10.1 months PFS PD-L1 <1%: pembrolizumab plus chemotherapy: 6.2 months; pembrolizumab plus placebo: 5.1 months PD-L1 1-49%: pembrolizumab plus chemotherapy: 9.2 months; pembrolizumab plus placebo: 4.9 months PD-L1 >/=50%: pembrolizumab plus chemotherapy: 11.1 months; pembrolizumab plus placebo: 4.8 months |
Pembrolizumab plus chemotherapy outperformed pembrolizumab plus placebo regardless of the PD-L1 status, however the magnitude of the effect was higher in tumors with high PD-L1 expression |
| Garon et al. (10) (KEYNOTE-001) | Assessment of long-term outcomes of pembrolizumab monotherapy in treatment-naïve and previously treated patients | OS in treatment-naïve patients: PD-L1 <1%: not evaluated (low number of patients) PD-L1 1–49%: 19.5 months PD-L1 >/=50%: 35.4 months OS in previously treated patients: PD-L1 <1%: 8.6 months PD-L1 1–49%: 8.5 months PD-L1 >/=50%: 15.4 months |
Pembrolizumab treatment was associated with improved OS in patients with PD-L1 expression in >/=50% tumor cells |
| Mok et al. (11) (KEYNOTE-042) | First-line therapy: pembrolizumab vs. chemotherapy for NSCLC with PD-L1 expression in >/=1% tumor cells | OS: PD-L1 >/=1%: pembrolizumab: 16.7 months; chemotherapy: 12.1 months PD-L1 >/=20%: pembrolizumab: 17.7 months; chemotherapy: 13.0 months PD-L1 >/=50%: pembrolizumab: 20.0 months; chemotherapy: 12.2 months PFS: PD-L1 >/=1%: pembrolizumab: 5.4 months; chemotherapy: 6.5 months PD-L1 >/=20%: pembrolizumab: 6.2 months; chemotherapy: 6.6 months PD-L1 >/=50%: pembrolizumab: 7.1 months; chemotherapy: 6.4 months |
Improvement of OS for pembrolizumab was observed both for PD-L1 >/=50% and >/=1% expression thresholds, however the magnitude of the effect was greater for the high expressors |
| Paz-Ares et al. (12) (KEYNOTE-407) | First-line therapy, squamous NSCLC: pembrolizumab or placebo plus chemotherapy | OS: PD-L1 <1%: pembrolizumab plus chemotherapy: 15.9 months; pembrolizumab plus placebo: 10.2 months PD-L1 1–49%: pembrolizumab plus chemotherapy: 14.0 months; pembrolizumab plus placebo: 11.6 months PD-L1 >/=50%: pembrolizumab plus chemotherapy: not reached; pembrolizumab plus placebo: not reached PFS: PD-L1 <1%: pembrolizumab plus chemotherapy: 6.3 months; pembrolizumab plus placebo: 5.3 months PD-L1 1–49%: pembrolizumab plus chemotherapy: 7.5 months; pembrolizumab plus placebo: 5.2 months PD-L1 >/=50%: pembrolizumab plus chemotherapy: 8.0 months; pembrolizumab plus placebo: 4.2 months |
Pembrolizumab plus chemotherapy outperformed pembrolizumab plus placebo regardless of the PD-L1 status |
| Nivolumab (IHC: 28-8) | |||
| Hellmann et al. (13) (CHECKMATE 227) | First-line therapy: nivolumab plus ipilimumab vs. nivolumab alone vs. chemotherapy for NSCLC with PD-L1 expression in >/=1% tumor cells; nivolumab plus ipilimumab vs. nivolumab plus chemotherapy vs. chemotherapy for NSCLC with PD-L1 expression in <1% tumor cells | OS: PD-L1 <1%: nivolumab plus ipilimumab: 17.2 months; nivolumab plus chemotherapy: 15.2 months; chemotherapy: 12.2 months PD-L1 >/=1%: nivolumab plus ipilimumab: 17.1 months; nivolumab alone: 15.7 months; chemotherapy: 14.9 months PD-L1 >/=50%: nivolumab plus ipilimumab: 21.2 months; nivolumab alone: 18.1 months; chemotherapy: 14.0 months PFS: PD-L1 <1%: nivolumab plus ipilimumab: 5.1 months; nivolumab alone: 5.6 months; chemotherapy: 4.7 months PD-L1 >/=1%: nivolumab plus ipilimumab: 5.1 months; nivolumab alone: 4.2 months; chemotherapy: 5.6 months PD-L1 >/=50%: nivolumab plus ipilimumab: 6.7 months; nivolumab alone: 5.6 months; chemotherapy: 5.6 months |
Nivolumab plus ipilimumab outperformed chemotherapy regardless of the PD-L1 status, however the difference was more pronounced in patients with PD-L1 expression in >/=50% tumor cells |
| Ready et al. (14) (CHECKMATE 568) | First-line therapy: nivolumab plus ipilimumab | PFS: PD-L1 <1%: 2.8 months PD-L1 >/=1%: 6.8 months PD-L1 >/=50%: 6.8 months |
PD-L1 expression was associated with higher rate of objective responses and longer PFS |
| Carbone et al. (15) (CHECKMATE 026) | First-line therapy: nivolumab vs. chemotherapy for NSCLC with PD-L1 expression in >/=1% tumor cells | OS: PD-L1 >/=1%: nivolumab: 13.7 months; chemotherapy: 13.8 months PD-L1 >/=5%: nivolumab: 14.4 months; chemotherapy: 13.2 months PD-L1 >/=50%: nivolumab: 15.9 months; chemotherapy: 13.9 months PFS: PD-L1 >/=1%: nivolumab: 4.2 months; chemotherapy: 5.8 months PD-L1 >/=5%: nivolumab: 4.2 months; chemotherapy: 5.9 months PD-L1 >/=50%: nivolumab: 5.4 months; chemotherapy: 5.8 months |
No predictive value for PD-L1 expression |
| Borghaei et al. (16) (CHECKMATE 057) | Nivolumab vs. docetaxel monotherapy in previously treated patients with non-squamous NSCLC | OS: PD-L1 <1%: nivolumab: 10.5 months; docetaxel: 10.1 months PD-L1 >/=1%: nivolumab: 17.7 months; docetaxel: 9.0 months PD-L1 >/=5%: nivolumab: 19.4 months; docetaxel: 8.1 months PD-L1 >/=10%: nivolumab: 19.9 months; docetaxel: 8.0 months PFS: PD-L1 <1%: nivolumab: 2.1 months; docetaxel: 3.6 months PD-L1 >/=1%: nivolumab: 4.2 months; docetaxel: 4.5 months PD-L1 >/=5%: nivolumab: 5.0 months; docetaxel: 3.8 months PD-L1 >/=10%: nivolumab: 5.0 months; docetaxel: 3.7 months |
Nivolumab outperformed docetaxel only in patients with PD-L1 expression in >/=1% tumor cells |
| Brahmer et al. (17) (CHECKMATE 017) | Nivolumab vs. docetaxel monotherapy in previously treated patients with squamous NSCLC | OS: PD-L1 <1%: nivolumab: 8.7 months; docetaxel: 5.9 months PD-L1 >/=1%: nivolumab: 9.3 months; docetaxel: 7.2 months PD-L1 >/=5%: nivolumab: 10.0 months; docetaxel: 6.4 months PD-L1 >/=10%: nivolumab: 11.0 months; docetaxel: 7.1 months |
No predictive role of the PD-L1 status |
| PFS: PD-L1 <1%: nivolumab: 3.1 months; docetaxel: 3.0 months PD-L1 >/=1%: nivolumab: 3.3 months; docetaxel: 2.8 months PD-L1 >/=5%: nivolumab: 4.8 months; docetaxel: 3.1 months PD-L1 >/=10%: nivolumab: 3.7 months; docetaxel: 3.3 months |
|||
| Atezolizumab (IHC: SP142) | |||
| Socinski et al. (18) (IMpower 150) | First-line therapy: atezolizumab plus carboplatin plus paclitaxel (ACP) vs. bevacizumab plus carboplatin plus paclitaxel (BCP) vs. atezolizumab plus BCP (ABCP) for non-squamous NSCLC | ABCP vs. BCP comparison, PFS: TC3 or IC3: 12.6 months vs. 6.8 months TC1/2/3 or IC1/2/3: 11.0 months vs. 6.8 months TC1/2 or IC1/2: 8.3 months vs. 6.6 months TC0/1/2 and IC0/1/2: 8.0 months vs. 6.8 months TC0 and IC0: 7.1 months vs. 6.9 months | Addition of atezolizumab to carboplatin, paclitaxel and bevacizumab improved PFS regardless of the PD-L1 status, however the magnitude of the effect was higher for tumors with high PD-L1 expression |
| Rittmeyer et al. (19) (OAK) | Atezolizumab vs. docetaxel monotherapy in previously treated NSCLC patients | OS: TC3 or IC3: 20.5 months vs. 8.9 months TC2/3 or IC2/3: 16.3 months vs. 10.8 months TC1/2/3 or IC1/2/3: 15.7 months vs. 10.3 months TC0 and IC0: 12.6 months vs. 8.9 months | Atezolizumab outperformed docetaxel regardless of the PD-L1 status, however the magnitude of the effect was higher for tumors with high PD-L1 expression |
| Fehrenbacher et al. (20) (POPLAR) | Atezolizumab vs. docetaxel monotherapy in previously treated NSCLC patients | OS: TC3 or IC3: 15.5 months vs. 11.1 months TC2/3 or IC2/3: 15.1 months vs. 7.4 months TC1/2/3 or IC1/2/3: 15.5 months vs. 9.2 months TC0 and IC0: 9.7 months vs. 9.7 months | Atezolizumab outperformed docetaxel only in patients with PD-L1 expression in >/=1% tumor cells or >/=1% tumor-infiltrating immune cells |
| Avelumab: (IHC: 73-10) | |||
| Barlesi et al. (21) (JAVELIN Lung 200) | Avelumab vs. docetaxel monotherapy in previously treated NSCLC patients | OS: PD-L1 >/=1%: avelumab: 11.4 months; docetaxel: 10.3 months PD-L1 >/=50%: avelumab: 13.6 months; docetaxel: 9.2 months PD-L1 >/=80%: avelumab: 17.1 months; docetaxel: 9.3 months |
Improved outcomes for avelumab were observed only in patients with high PD-L1 expression |
| Gulley et al. (22) (JAVELIN Solid Tumor) | Avelumab in previously treated NSCLC patients | OS: PD-L1 <1% tumor cells: 4.6 months PD-L1 >/=1% tumor cells: 8.9 months PD-L1 >/=5% tumor cells: 10.6 months PD-L1 >/=25% tumor cells: 8.4 months PD-L1 </=10% immune cells in hot-spots: 8.5 months PD-L1 >/=10% immune cells in hot-spots: 8.9 months PFS: PD-L1 <1% tumor cells: 5.9 weeks PD-L1 >/=1% tumor cells: 12.0 weeks PD-L1 >/=5% tumor cells: 11.9 weeks PD-L1 >/=25% tumor cells: 11.9 weeks PD-L1 </=10% immune cells in hot-spots: 11.3 weeks PD-L1 >/=10% immune cells in hot-spots: 8.4 weeks |
Improved outcomes for avelumab were observed when PD-L1 expression in >/=1% tumor cells was used as a threshold |
| Durvalumab (IHC: SP263) | |||
| Rizvi et al. (23) (MYSTIC) | First-line therapy: durvalumab with or without tremelimumab vs. standard chemotherapy | OS: PD-L1 <1%: durvalumab plus tremelimumab: 11.9 months; durvalumab alone: 10.1 months; chemotherapy: 10.3 months PD-L1 >/=1%: durvalumab plus tremelimumab: 10.9 months; durvalumab alone: 14.6 months; chemotherapy: 12.3 months PD-L1 25–49%: durvalumab plus tremelimumab: 10.5 months; durvalumab alone: 11.1 months; chemotherapy: 13.3 months PD-L1 >/=50%: durvalumab plus tremelimumab: 15.2 months; durvalumab alone: 18.3 months; chemotherapy: 12.7 months |
Improved outcomes for durvalumab were observed only in patients with high PD-L1 expression |
| Paz-Ares et al. (24) (PACIFIC) | Durvalumab vs. placebo after chemoradiotherapy in unresectable stage III NSCLC | OS: PD-L1 <1%: durvalumab 33.1 months; placebo: 45.6 months PD-L1 1–24%: durvalumab 43.3 months; placebo: 30.5 months PD-L1 >/=25%: durvalumab: not reached; placebo: 21.1 months PFS: PD-L1 <1%: durvalumab 10.7 months; placebo: 5.6 months PD-L1 1–24%: durvalumab: not reached; placebo: 9.0 months PD-L1 >/=25%: durvalumab 17.8 months; placebo: 3.7 months |
Improved PFS for durvalumab was observed across all subgroups; improved OS for durvalumab was seen for patients with PD-L1 expression in >/=1% tumor cells |
| Garassino et al. (25) (ATLANTIC) | Durvalumab as a third-line or later treatment in NSCLC patients | OS: Cohort EGFR+/ALK+: PD-L1 <25%: 9.9 months PD-L1 >/=25%: 13.3 months Cohort EGFR-/ALK-: PD-L1 <25%: 9.3 months PD-L1 >/=25%: 10.9 months Cohort PD-L1>/=90%: not reached PFS: Cohort EGFR+/ALK+: PD-L1 <25%: 1.9 months PD-L1 >/=25%: 1.9 months Cohort EGFR-/ALK-: PD-L1 <25%: 1.9 months PD-L1 >/=25%: 3.3 months Cohort PD-L1>/=90%: 2.4 months |
PD-L1 expression was associated with improved outcomes |
OS, overall survival; PFS, progression-free survival; IHC, immunohistochemistiry; TC, tumor cells; IC, immune cells; the details for TC and IC scoring are explained in (20).