Table 2.
Immune checkpoint inhibitors investigated for the management of recurrent/metastatic HNSCC.
| Drug (target) | Study name (Phase of the study) | Key findings | PD-L1 expression location and cut-off | ORR (%) | OS (HR) a | ||
|---|---|---|---|---|---|---|---|
| PD-L1+ | PD-L1- | PD-L1+ | PD-L1– | ||||
| Pembrolizumab (PD-1) | KEYNOTE-012 (Phase I) (45, 80) |
• PFS: 23% • OS: 59% • Greater ORR in PD-L1-positive patient versus PD-L1-negative patients (p = 0.021) |
TC + IC ≥ 1% | 22.00% | 4.00% | Not applicable | Not applicable |
| TC ≥ 1% | 17.00% | 7.00% | |||||
| KEYNOTE-040 (Phase III) (139, 140) |
• Pembrolizumab vs standard of care OS: 8·4 vs 6.9 months; HR, 0·80, 0·65–0·98; p=0·0161 |
TC+ IC (CPS ≥ 1) |
17.30% | Not available | 0.74 (p = 0.0049) |
Not available | |
| TC (TPS ≥ 50) |
26.60% | Not available | 0.53 (p = 0.0014) |
Not available | |||
| KEYNOTE-048 (Phase III) (18, 19) |
• Pembrolizumab alone improved OS compared to cetuximab with chemotherapy in patients with CPS ≥20 (14.9 vs 10.7 months; p=0·0007) and CPS ≥ 1 (12.3 vs 10.3 months; p=0·008) • Pembrolizumab with CT improved OS compared to cetuximab with chemotherapy in the total population (13·0 months vs 10·7 months, p=0·0034) |
TC + IC (CPS ≥ 1) |
19.10% | Not available | 0.78 (p = 0.0086) |
Not available | |
| TC + IC (CPS ≥ 20) |
23.30% | Not available | 0.61 (p= 0.0007) |
Not available | |||
| Nivolumab (PD-1) |
CheckMate-141 (Phase III) (141, 142) | • OS was significantly longer with nivolumab than with standard therapy (7.5 vs 5.1 months; HR, 0.70; 97.73% CI, 0.51 to 0.96; p=0.01) | TC ≥ 1% | 17.00% | 11.80% | 0.55 | 0.73 |
| Durvalumab (PD-L1) | MEDI4736-1108 (Phase II) (143) |
• 6 and 12-month OS was 62% (95% CI: 48-74) and 42% (95% CI: 27-55), respectively | TC ≥ 25% | 18.00% | 8.00% | Not applicable | Not applicable |
| HAWK (Phase II) (144) | • Median PFS and OS for treated patients were 2.1 months (95% CI: 1.9-3.7) and 7.1 months (95% CI: 4.9-9.9), respectively | TC ≥ 25% | 16.20% | Not available | |||
| CONDOR (Phase II) (145) |
• ORR was 7.8% (95% CI: 3.78%-13.79%) in durvalumab + tremelimumab arm, 9.2% (95% CI: 3.46%-19.02%) for durvalumab monotherapy, and 1.6% (95% CI: 0.04%-8.53%) for tremelimumab monotherapy | TC < 25% | Not available | 6.00% | |||
| Atezolizumab (PD-L1) | GO27831 (Phase I) (146) |
• ORR: 22% | IC 2/3: > 5% | 24.00% | Not available | Not applicable | Not applicable |
| IC 0/1: < 5% | 14.00% | ||||||
CI, confidence interval; CPS, combined positive score; CT, chemotherapy HR, hazard ratio; ICs, immune cells; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; TCs, tumor cells; TPS, tumor proportion score.
a
HR for OS resulting from: nivolumab and pembrolizumab versus investigator’s choice of chemotherapy (Docetaxel, Methotrexate and Cetuximab) in the CHECKMATE-141 and KEYNOTE-040 studies, respectively; pembrolizumab monotherapy versus EXTREME regimen in the KEYNOTE-048 study; durvalumab versus tremelimumab plus durvalumab in the CONDOR study.