Table 2.
The predictive value of PD-L1 for PD-1/PD-L1 inhibitors in TNBC.
| Application | Agents | Study | Combined Drug | N | Scoring Criteria | Group | Results |
|---|---|---|---|---|---|---|---|
| Early TNBC | Pembro | KEYNOTE-522 (29) | Pembro/placebo +chemotherapyg |
602 | CPS:1 | •PD-L1+ | • pCR: 68.9% vs 54.9% |
| •PD-L1- | • pCR: 45.3% vs 30.3% | ||||||
| Atezo | Impassion031 (23) | Atezo/placebo +chemotherapyh |
333 | PD-L1 in IC: 1% | • PD-L1 + | • pCR: 69% (95% CI, 57-79) vs 49% (95% CI, 38-61) | |
| • PD-L1 - | • pCR: 48% vs 34% | ||||||
| Advanced TNBC | Atezo | Impassion130 (18, 37) | Atezo/placebo + nab-paclitaxel |
902 | PD-L1 in IC: 1% | • PD-L1 + | • ORR: 58.9% (51.5-66.1) vs 42.6% (35.4-50.1) HR=1.96 (1.29-2.98) |
| • m PFS: 7.5 (95%CI, 6.7-9.2) mo vs 5.0 (95%CI, 3.8-5.6) mo HR=0.64 (0.51-0.80) | |||||||
| • m OS: 25.4 (95% CI, 19.6-30.7)mo vs 17.9 (95%CI, 13.6-20.3)mo HR=0.67 (0.53-0.86) | |||||||
| • PD-L1 - | • m PFS: 5.6 mo vs 5.6 mo HR=0.95 (0.79-1.15) |
||||||
| • m OS: 19.7 mo vs 19.7 mo HR=1.05 (0.87-1.28) | |||||||
| Atezo | Impassion131 (21) | Atezo/ placebo +paclitaxel |
651 | PD-L1 in IC: 1% | • PD-L1 + | • m PFS: 6.0 (95% CI 5.6-7.4) mo vs 5.7 (95% CI 5.4-7.2) mo HR=0.82 (0.60-1.12) |
|
| • Final OS: 22.1 (95% CI 19.2-30.5) mo vs 28.3 (95% CI 19.1-NE) mo HR=1.11(0.76-1.64) | |||||||
| Advanced TNBC | Pembro | KEYNOTE-012 (30) | single-agent pembro | 111 | PD-L1 in IC: 1% | • PD-L1+ | • ORR: 18.5% (95% CI, 6.3-38.1) |
| • m PFS: 1.9 (95% CI, 1.7-5.5) mo | |||||||
| • m OS: 11.2 (95% CI, 5.3- (not reached)) mo | |||||||
| Pembro | KEYNOTE-086 (31, 32) | single-agent pembro | Cohort A:170 B:84 |
CPS: 1 | • Cohort A (PD-L1+) |
• ORR: 5.7% (95%CI, 2.4-12.2) | |
| • m PFS: 2.0 (95%CI, 1.9-2.1) mo | |||||||
| • m OS: 8.8 (95%CI, 7.1-11.2) mo | |||||||
| • Cohort A (PD-L1-) |
• ORR: 4.7% (95%CI, 1.1-13.4) | ||||||
| • m PFS: 1.9 (95%CI, 1.7-2.0) mo | |||||||
| • m OS: 9.7 (95%CI, 6.2-12.6) mo | |||||||
| • Cohort B (PD-L1+) |
• ORR: 21.4% (95%CI, 13.9-31.4) | ||||||
| • m PFS: 2.1 (95%CI, 2.0-2.2) mo | |||||||
| • m OS: 18.0 (95%CI, 12.9, 23.0) mo | |||||||
| Pembro | KEYNOTE-150 (34) | Eribulin +pembro | 107 | CPS: 1 | •PD-L1+ | •ORR: 25.7% (95%, 12.9-40.8) | |
| •m PFS: 4.1 (95%CI, 2.1-4.8) mo | |||||||
| •PD-L1- | •ORR: 25.0% (95%, 12.5-39.8) | ||||||
| •m PFS: 4.1 (95%CI, 2.3-6.3)mo | |||||||
| Advanced TNBC | Pembro | KEYNOTE-119 (20) | Pembro/ chemotherapyi | 1098 | CPS: 1, 10, 20 | •CPS ≥1 | •ORR: 12.3% (95%CI, 8.1-17.6) vs9.4% (95%CI, 5.8-14.3) |
| •m OS: 10.7 (95% CI, 9.3-12.5) mo vs 10.2 (95% CI, 7.9-12.6) mo HR=0.86(0.69-1.06) | |||||||
| •CPS ≥10 | •ORR: 17.7% (95%CI, 10.7-26.8) vs9.2% (95%CI, 4.3-16.7) | ||||||
| •m OS: 12.7(95% CI, 9.9-16.3) mo vs 11.6 (95% CI, 8.3-13.7) mo HR=0.78(0.57-1.06) | |||||||
| •CPS ≥20 | •ORR: 26.0% vs12.0% | ||||||
| •m OS: 14.9 mo vs 12.5 mo HR=0.58(0.38-0.88) | |||||||
| Pembro | KEYNOTE-355 (19, 33) | Pembro/placebo + chemotherapyj |
847 | CPS: 1 and 10 | •CPS ≥1 | •ORR: 44.9% (95% CI, 40.1-49.8) vs 38.9% (95% CI, 32.2-45.8) | |
| •m PFS: 7.6 (95% CI, 6.6-8.0) mo vs 5.6 (95% CI, 5.4-7.4) mo HR=0.75 (0.62-0.91) | |||||||
| •m OS: 17.6(95% CI, 15.5-19.5) mo vs 16.0 (95% CI, 12.8-17.4) mo HR=0.86 (0.72-1.04) | |||||||
| •CPS ≥10 | •ORR: 52.7% (95% CI, 45.9-59.5) vs 40.8% (95% CI, 31.2-50.9) | ||||||
| •m PFS: 9.7 (95% CI, 7.6-11.3) mo vs 5.6 (95% CI, 5.3-7.5) mo HR=0.66 (0.50-0.88) | |||||||
| •m OS: 23.0(95% CI, 19.0-26.3) mo vs 16.1 (95% CI, 12.6-18.8) mo HR=0.73(0.55-0.95) | |||||||
| Advanced Breast cancer | Avelumab | JAVELIN (22) | single-agent avelumab | 168 (58 was TNBC) |
•PD-L1 in TCa: 1, 5 and 25% •PD-L1 in ICb: 10% |
• TNBCc
(PD-L1+ vs PD-L1-) |
•ORR: 22.2% vs. 2.6% |
| • ≥1% TCd
(PD-L1+ vsPD-L1-) |
•ORR: 3.4% (95% CI, 0.3-8.2) vs 3.9% (95% CI, 0.5-13.5) | ||||||
| •m PFS:5.9 (95% CI, 5.7-6.0) weeks vs 6.0 (95% CI, 5.9-6.0) weeks HR=1.183 (0.815-1.716) | |||||||
| •m OS: 6.5 (95% CI, 3.7-9.2) mo vs 8.3 (95% CI 6.3, ne) mo HR=1.331 (0.815-2.174) | |||||||
| • ≥5% TCe
(PD-L1+ vsPD-L1-) |
•ORR: 4.3% (95% CI, 0.1, 21.9) vs 2.7% (95% CI, 0.6-7.6) | ||||||
| •m PFS:6.0 (95% CI, 5.7-7.1) weeks vs 5.9 (95% CI, 5.9-6.0) weeks HR=0.782 (0.473-1.290) | |||||||
| •m OS: 6.5 (95% CI, 2.2-ne) mo vs 7.1 (95% CI, 5.1-11.3) mo HR=1.057 (0.556-2.010) | |||||||
| • ≥25% TC f
(PD-L1+ vsPD-L1-) |
•ORR: 0 (95% CI, 0-70.8) vs 3 (95% CI, 0.8-7.5) | ||||||
| •m PFS:6.0 (95% CI 5.4- ne) weeks vs 5.9 (95% CI 5.9- 6.0) weeks HR=0.695 (0.172-2.813) | |||||||
| •m OS: 9.2 (95% CI, ne-ne) mo vs 6.8 (95% CI, 4.9-10.8) mo HR=0.441 (0.061-3.177) | |||||||
| • ≥10% IC c
(PD-L1+ vsPD-L1-) |
•ORR: 16.7 (95% CI, 2.1-48.4) vs 1.6 (95% CI, 0.2-5.7) | ||||||
| •m PFS:6.1 (95% CI, 2.3-24,1) weeks vs 5.9 (95% CI, 5.9-6.0) weeks HR=0.656 (0.341-1.263) | |||||||
| •m OS: 11.3 (95% CI, 1.4-ne) mo vs 6.8 (95% CI, 4.7-9.2) mo HR=0.620 (0.250-1.541) |
N, number of patients; TC, tumor cells; IC, immune Cells; m PFS, median PFS; mo, months; m OS, median OS; HR, hazard ratio, HR (95%CI); Pembro, Pembrolizumab; Atezo, Atezolizumab.
a: the percentages of tumor cells expressing PD-L1: 1 and 5% thresholds with any staining intensity and a 25% threshold with moderate to high staining; b: 10% of immune cells expressing PD-L1 at any staining intensity in tumor tissue; c: ITT population, PD-L1+: PD-L1 expression≥10% immune cells; d: ITT population, PD-L1+: PD-L1 expression≥1% tumor cells; e: ITT population, PD-L1+: PD-L1 expression≥5% tumor cells; f: ITT population, PD-L1+:PD-L1 expression≥25% tumor cells; g: paclitaxel+carboplatin; h: nab-paclitaxel + doxorubicin+ cyclophosphamide; i: received investigator-choice (capecitabine, eribulin, gemcitabine, or vinorelbine); j: nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin.