Table 2.
Trials showing the use of the combined positivity score (CPS) in HER2 negative upper gastrointestinal malignancies.
| TRIAL ARM | PD-L1 CPS (No. of Patients Receiving Pembrolizumab or Nivolumab) | 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-061 (pre-treated gastric and GOJ cancer Taxol vs. Pembro) [39] | All patients (296) | 11 | 1.6 | 1.34 (1.12–1.60) | 6.7 (5.4–8.9) | 0.94 (0.79–1.12) | |
| KEYNOTE-061 | CPS ≥ 1 (196) | 16 | 1.5 | 1.27 1.03–1.57) | 9.1 | 0.82, 0.66–1.03; one-sided p = 0.0421 | FDA (gastric cancer 3rd line) |
| KEYNOTE-061 | CPS ≤ 1 (99) | 2 | |||||
| KEYNOTE-061 (post-hoc analysis) | CPS ≥ 10 (53) | 24.5 | FDA (gastric cancer of GOJ cancer 2nd line) | ||||
| KEYNOTE-062 (Pembro alone vs. Pembro + Chemo vs. Chemo alone first line gastric AC) [40] | Pembro Alone (256) | 14.8 | 10.6 (7.7–13.8) | 0.91 (99.2% CI 0.69–1.18) | |||
| Pembro Alone CPS > 1 |
2 (1.5–2.8) | 1.66 (1.37–2.01) | 0.91 (0.74–1.1) | ||||
| Pembro Alone CPS ≥ 10 |
23 | 2.9 (1.6–5.4) | 1.10 (0.79–1.51) | 17.4 (9.1–23.1) | 0.69 (0.49–0.97) | ||
| Pembro + Chemo (250) | 37.2 | 12.5 (10.8–13.9) | 0.85 (0.7–1.03) | ||||
| Pembro + Chemo CPS ≥ 1 | |||||||
| Pembro + Chemo CPS ≥ 10 | 6.9 (5.7–7.3) | 0.84 (0.7–1.02) | 12.3 (9.5–14.8) | 0.85 (0.62–1.17, 0.16) | |||
| KEYNOTE-180 (Pre-treated Oesophageal AC and SCC) [41] | 9.9 (5.2–16.7) | ||||||
| CPS < 10 (63) | 6 (2–16) | 2.0 (1.9–2.1) | 5.4 (3.9–6.3) | ||||
| CPS ≥ 10 (58) | 14 (6–25) | 2.0 (1.9–2.2) | 6.3 (4.4–9.3) | ||||
| SCC CPS ≥ 10 (35) | 20 | FDA | |||||
| KEYNOTE-181 (pre-treated AC and SCC Pembro vs. chemo) [37] | All Patients (314) | 13.1 (9.5–17.3) | 2.1 (2.1–2.2) | 1.11 (0.94–1.31) | 7.1 | 0.89 (0.75–1.05, 0.0560) | |
| CPS ≥ 10 | 21.5 (14.1–30.5) | 2.6 (2.1–4.1) | 0.73 (0.54 to 0.97) | 9.3 (6.6–12.5) | 0.69 (0.52–0.93, 0.0074) | FDA | |
| SCC | 16.7 (11.8–22.6) | 2.2 (2.1–3.2) | 0.92 (0.75–1.13) | 8.2 | 0.78 (0.63–0.96, 0.0095) | ||
| SCC CPS < 10 | 11.9 | 2.1 (2.1–2.4) | 7.3 (5.7–9.2) | ||||
| AC CPS < 10 | 3.3 | 2.1 (1.9–2.1) | 5.1 (4.1–7.1) | ||||
| ATTRACTION-2 (pretreated gastric or GOJ AC, Nivo vs. Placebo) [42] |
N/A (493 received Nivo) | 11.9 | 1.61 (1.54–2.30) | 0.60 (0.49–0.75, < 0.0001) | 5.26 (4.60–6.37) | 0.62 (0.51–0.76, p < 0.0001) | FDA |
| ATTRACTION-3 (pre-treated oesophageal SCC, Nivo vs. placebo) [43] | N/A (210 received Nivo) | 10.9 (9.2–13.3) | 0.77 (0.62–0.96, 0.019) | FDA, EMA | |||
| KEYNOTE -590 (Advanced first line oesophageal or GOJ cancer, chemo and Pembro, 73.5% SCC, 25.5% AC) [44] |
All patients (373) | 45.0 (39.9–50.2) | 6.3 (6.2–6.9) | 0.65 (0.55–0.76; p < 0.0001). | 12.4 (10.5, 14.0) | 0.73 (0.62–0.86, <0.0001) | FDA |
| SCC CPS ≥ 10 (143) | 7.3 (6.2–8.2) | 0.53 (0.40–0.69) | 13.9 (11.1–17.7) | 0.57 (0.43–0.75, <0.0001) | FDA, | ||
| All SCC (274) | 7.5 | 12.6 (10.2–14.3) | 0.72 (0.60–0.88, 0.0006) | FDA | |||
| All CPS ≥ 10 (186) | 7.5 (6.2–8.2) | 13.5 (11.1–15.6) | 0·62 (0.49–0.78, p < 0.0001) | FDA, | |||
| AC CPS ≥ 10 (43) | 8.0 (6.0–8.3) | 0.49 (0.30–0.81) | 12.1 (9.6–18.7) | 0.83 (0.52–1.34) | FDA, EMA | ||
| AC CPS < 10 (54) | 6.3 (5.6–8.3) | 0.76 (0.49–1.19) | 12.7 (8.1–16.1) | 0.66 (0.42–1.04) | |||
| CheckMate 649 (Nivo + chemo vs. chemo alone in first line gastric, GOJ, oesophageal AC) [45] | All patients (603) | 58 (54–62) | 7.7 (7.1–8.5) | 0.77 (0.68–0.87) | 13.8 (12.6–14.6) | 0.8 (0.68–0.94, <0.0002) | FDA |
| CPS ≥ 5 (473) | 60 (55–65) | 7.7 (7.0–9.1) | 0·68 (98% CI 0·56–0·81, <0·0001) | 14.4 (13.1–16.2) | 0.71 (98.4% CI 0·59–0·86, <0.0001) | FDA, EMA | |
| CPS ≥ 1 (641) | 60 | 7.5 (7.0–8.4) | 0.74 (0.65–0.85) | 14.1 (11.6–15) | 0.77 (99.3% CI 0.064–0.92, <0.0001) | FDA | |
| CPS < 5 | 55 | 7.5 | 0.93 (0.76–1.12) | 12.4 | 0.94 (0.78–1.13) | FDA | |
| CPS < 1 (140) | 51 | 8.7 | 0.93 (0.69–1.26) | 13.8 | 0.79 (0.7–0.89) | FDA |