Table 1.
Characteristics of selected randomized trials evaluating chemoradiation with and without immune-checkpoint inhibition.
| Trial | Patient population | Standard of care (SOC) | Total RT dose | Immunotherapy intervention | Comparative arm | Outcome |
|---|---|---|---|---|---|---|
| PACIFIC (6, 7) | Locally advanced unresectable NSCLC (N = 709) | Platinum-based chemoradiation | 54–66 Gy | SOC + durvalumab (anti–PD-L1) 10 mg/kg every 2 weeks for up to 12 months, start 1–42 days after RT completion | SOC + placebo | mPFS 16.8 months (SOC-durva) vs. 5.6 months (SOC-placebo); HR 0.52; 95% CI, 0.42–0.65; P < 0.001—Response rate 28.4% (SOC-durva) vs. 16.0% (SOC-placebo); P < 0.001 |
| GORTEC-REACH (9) | Locally advanced unresectable HNSCC (N = 707) | Cisplatin- or cetuximab-based chemoradiation | 70 Gy | Cetuximab-based chemoradiation + avelumab (anti–PD-L1) 10 mg/kg at day −7 and every 2 weeks during RT followed by avelumab for up to 12 months | SOC | Cisplatin-unfit patients: 2-year PFS rate 44% (Cetux-RT-Ave) vs. 31% (Cetux-SOC); HR 0.85; P = 0.15); 2-year OS rate 58% (Cetux-RT-Ave) vs. 54% (Cetux-SOC); HR 1.08, P = 0.69)/cisplatin-fin patients: 1-year PFS rate 64% (Cetux-RT-Ave) vs. 73% (SOC-cisplatin); HR 1.27, 0.83–1.93 |
| PembroRad (8, 10) | Locally advanced unresectable HNSCC (N = 707) | Cetuximab-based chemoradiation | 70 Gy | Radiotherapy + pembrolizumab (anti–PD-1) every 3 weeks during RT | SOC | 2-year PFS rate 40% (Cetux-RT) vs. 42% (Pembro-RT); HR = 0.83, 95% CI, 0.53–1.29, P = 0.41/2-year OS rate 55% (Cetux-RT) vs. 62% (Pembro-RT); HR = 0.83; 95% CI, 0.49–1.40; P = 0.49 |
| KEYNOTE-412 (11) | Locally advanced unresectable HNSCC (N = 804) | Cisplatin-based chemoradiation | 70 Gy | SOC + pembrolizumab (anti–PD-1) every 3 weeks during RT followed by pembrolizumab every 3 weeks for up to 14 cycles | SOC + placebo | 2-Year EFS rate 63.2% (SOC-pembro) vs. 56.2% (SOC-placebo); HR 0.83; 95% CI, 0.68–1.03; P = 0.0429 (superiority threshold = 0.0242)/2-year OS rate 77.9% (SOC-pembro) vs. 76.8 (SOC-placebo); HR 0.90; 95% CI, 0.71–1.15; P = NS |
Note: Whether immunotherapy was administered sequentially or concomitantly to chemoradiation is underlined.
Abbreviations: EFS, event-free survival; HR, hazard ratio; HNSCC, head and neck squamous cell carcinoma; (m)PFS, (median) progression-free survival; NS, nonsignificant; NSCLC, non–small cell lung cancer; SOC, standard of care.