Table 1.
Tumour proportion score (TPS) using Dako 22C3 immunohistochemistry as a biomarker of Pembrolizumab efficacy in first-line metastatic EGFR and ALK wild type NSCLC compared to cytotoxic chemotherapy alone. Trials were selected to show the evolution of pembrolizumab from salvage to first line therapy and the limitations of TPS.
| TRIAL ARM | PD-L1 TPS (Number of Patients Receiving Pembrolizumab) | Overall Response Rate (95% CI) (%) | Median PFS in Months (95% CI) | PFS HR Compared to Chemo Alone (95% CI, p-Value) | Median OS in Months (95% CI) | OS HR Compared to Chemo Alone (95% CI, p-Value) | Approval |
|---|---|---|---|---|---|---|---|
| KEYNOTE-024 Single Agent Pembrolizumab (Pre-treated AC and SCC [25,30,31,32] | ≥50% (154) |
44.8 | 10.3 | 0.5 (0.37–0.68, <0.001) | 26.3 (95% CI 18.3–40.4) | 0.62 (0.48–0.81, 0.002) | Ireland, EMA [33], FDA |
| KEYNOTE-042 Single Agent Pembrolizumab (First Line AC and SCC) [26] | All Patients (636) | 16.7 | 0.81 (0.71–0.93, 0.0036) | FDA | |||
| KEYNOTE 042 [26] | ≥50% (298) |
39 (34–45) | 7.1 (5.9–9) | 0.81 (0.67–0.99, 0.017) | 20 (15–24.9) | 0.69 (0.56–0.85, 0.003) | Ireland, EMA, FDA |
| KEYNOTE 042 [26] | ≥20% (412) |
33 (29–38) | 6.2 (5.1–7.8) | 0.94 (0.8–1.11,) | 17.7 (15.3–22.1) | 0.77 (0.64–0.92, 0.002) | FDA |
| KEYNOTE 042 [26] | ≥1% (636) |
27 (24 -31) | 5.4 (4.3–6.2) | 1.07 (0.94–1.21) | 16.7 (13.9–19.7) | 0.81 (0.71–0.93, 0.0018) | FDA |
| KEYNOTE 042 [26] | 1–49% (338) |
13.4 (10.7–18.2) | 0.92 (0.77–1.11,) | FDA | |||
| Pembrolizumab and Chemotherapy (First Line AC) KEYNOTE 189 [34,35] | All Patients (410) |
48 (43.1–53) | 9 (8.1–9.9) | 0.48 (0.4–0.58) | 22 (19.5–25.2) | 0.56 (0.45–0.70) | Ireland, EMA, FDA |
| KEYNOTE 189 [34,35] | ≥50% (132) |
62.1 (53.3–70.4) | 11.1 (9.1–14.4) | 0.36 (0.26 -0.51) | NR (20.4–NR) | 0.59 (0.39–0.86) | |
| KEYNOTE 189 [34,35] | 1–49% (128) |
49.2 (40.3–58.2) | 9.2 (7.8–13.1) | 0.51 (0.36–0.73) | 21.8 (17.7–25.9) | 0.62 (0.42–0.92) | |
| KEYNOTE 189 [34,35] | <1% (127) |
32.3 (24.3–41.2) | 6.2 (4.9–8.1) | 0.64 (0.47–0.89) | 17.2 (13.8–22.8) | 0.52 (0.36–0.74) | |
| Pembrolizumab and Chemotherapy (First Line SCC) KEYNOTE-407 [36] | All Patients (278) |
57.9% (51.9–63.8) | 6.4 (6.2–8.3) | 0.56 (0.45–0.70; <0.001) | 15.9 (13.2–NE) | 0.64; (0.49–0.85; <0.001) | Ireland, EMA, FDA |
| ≥50% (73) |
60.3 (48.1–71.5) | 8.0 (6.1–10.3) | 0.37 (0.24–0.58) | NR (11.3–NE) | 0.64 (0.37–1.10) | ||
| 1–49% (103) |
49.5 (39.5–59.5) | 7.2 (6.0–11.4) | 0.56 (0.39–0.8) | 14.0 (12.8–NE) | 0.57 (0.36–0.90) | ||
| ≥1% (183) |
0.49 (0.38–0.65) | ||||||
| <1% (95) |
63.2 (52.6–72.8) | 6.3 (6.1–6.5) | 0.68 (0.47–0.98) | 15.9 (13.1–NE) | 0.61 (0.38–0.98) |
Table 1 Legend; immunohistochemistry (IHC) progression-free survival (PFS), hazard ratio (HR), overall survival (OS), confidence interval (CI), tumour proportion score (TPS), p-value only listed if significant, not reached (NR), not estimable (NE). Most recent publication used where applicable. Note that the populations in KEYNOTE 042 overlap and that most of the benefit is in the group with TPS ≥ 50%. European Medicines Agency, Food and Drug Administration (USA). Ireland—funded by National Cancer Control Program in this indication. Not estimable (NE). Adenocarcinoma (AC), squamous cell carcinoma (SCC).