Table 1.
Representative clinical trial results of targeted therapies in HNC
| Target | Treatment | Condition | Phase | Enrollment | Median follow-up | Local control or response rate | OS (months) | PFS (months) | NCT number |
|---|---|---|---|---|---|---|---|---|---|
| EGFR | a. RT + cetuximab; b. RT | LA-SCCHN | 3 | 424 | 54.0 months | 3-year local control: 47% vs. 34% | 49.0 vs. 29.3 | 17.1 vs. 12.4 | NCT0000422725 |
| EGFR | a. RT + cetuximab; b. RT + cisplatin | LA-SCCHN | 2 | 88 | 19.3 months | 2-year local control: 53% vs. 80% | 2-year: 68% vs. 78% | 2-year MFS: 97% vs. 90% | NCT01216020378 |
| EGFR | a. RT + cetuximab; b. RT + cisplatin | LA-SCCHN | 3 | 298 | 3.2 | 3-year LRF: 23% vs. 9% | 3-year: 78% vs. 88% | 3-year EFS: 67% vs. 85% | NCT01969877380 |
| EGFR | a. RT + cetuximab; b. RT + cisplatin | HPV (+) OPC | 3 | 334 | 25.9 months | Locoregional recurrences: 12% vs 3% | 2-year: 89·4% vs 97·5% | – | ISRCTN33522080381 |
| EGFR | a. RT + cetuximab; b. RT + cisplatin | HPV (+) OPC | 3 | 805 | 4.5 years | 5-year LRF: 17.3% vs. 9.9% | 5-year: 77.9% vs. 84.6% | 5-year: 67.3% vs. 78.4% | NCT01302834382 |
| EGFR | a. TPF/TP + cetuximab ICT; b. TPF/TP ICT | advanced laryngeal/hypopharyngeal cancer | 2 | 180 | 24 months | – | 24-month: 62% vs. 58% | 24-month LFS: 47.1.% vs. 46.6% | NCT00508664389 |
| EGFR | a. TPF ICT; b. TPC ICT | LA-SCCHN | 2 | 100 | 400 days | CR: 32.7% vs. 49.0% | 400-day: 78.5% vs. 86.1% | 400-day: 66.5% vs. 70.0% | EudraCT-No. 2011-005540-99390 |
| EGFR | a. Cisplatin + cetuximab; b. cisplatin + placebo | R/M-SCCHN | 3 | 117 | 31 months | ORR: 26% vs. 10% | 9.2 vs. 8.0 | 4.2 vs. 2.7 | 407 |
| EGFR | a. PF + cetuximab; b. PF | R/M-SCCHN | 3 | 442 | 18.2 vs. 19.1 months | ORR: 36% vs. 20% | 10.1 vs. 7.4 | 5.6 vs. 3.3 | NCT0012246026 |
| EGFR | Paclitaxel, carboplatin + cetuximab | R/M-SCCHN | 2 | 47 | 20 months | ORR: 40% | 14.7 | 5.2 | UMIN000010507412 |
| EGFR | a. PCF; b. Cetuximab + docetaxel + cisplatin | R/M-SCCHN | 2 | 541 | 30.2 vs. 34.4 months | ORR: 59% vs. 57% | 13.4 vs. 14.5 | 6.2 vs. 6.0 | NCT02268695414 |
| EGFR | a. RT + panitumumab; b. RT + cisplatin | LA-SCCHN | 2 | 152 | 107.5 vs. 123 weeks | 2-year local control: 51% vs. 61% | 2-year: 63% vs. 71% | 2-year: 41% vs. 62% | NCT00547157393 |
| EGFR | a. PF + panitumumab; b. PF | R/M-SCCHN | 3 | 657 | 44 vs. 35 months | Objective response: 36% vs. 25% | 11.1 vs. 9.0 | 5.8 vs. 4.6 | NCT00460265419 |
| EGFR | a. RT + cisplatin + nimotuzumab; b. RT + cisplatin | LA-SCCHN | 3 | 536 | 39.13 months | 2-year LRC: 67.5% vs. 57.6% | 2-year: 63.8% vs. 57.7% | 2-year: 61.8% vs. 50.1 | CTRI/2014/09/004980398 |
| EGFR | PF + nimotuzumab | R/M-NPC | 2 | 35 | 13.2 months | ORR: 71.4% | 16.3 | 7.0 | NCT01616849422 |
| EGFR | Gefitinib + fluorouracil + hydroxyurea +RT | LA-SCCHN | 3 | 69 | 3.5 years | CR: 90% | 4-year: 74% | 4-year: 72% | 402 |
| a. Afatinib; b. methotrexate | R/M-SCCHN | 3 | 483 | 6.7 months | ORR: 10% vs. 6% | 6.8 vs. 6.0 | 2.6 vs. 1.7 | NCT01345682429 | |
| VEGF(R) | a. Sorafenib; b. placebo | LA- or R/M-thyroid cancer | 3 | 417 | 16.2 months | ORR: 12.2% vs. 0.5% | NR | 10.8 vs. 5.8 | NCT00984282439 |
| VEGF(R) | sorafenib + PF | R/M-NPC | 2 | 54 | 19.0 months | ORR: 77.8% | 7.2 | 11.8 | 442 |
| VEGF(R) | a. Lenvatinib; b. placebo | Radioiodine-refractory thyroid cancer | 3 | 392 | 17.1 months | ORR: 64.8% vs. 1.5% | – | 18.3 vs. 3.6 | NCT01321554443 |
| VEGF(R) | a. Apatinib; b. placebo | LA- or R/M-thyroid cancer | 3 | 92 | 18.1 months | ORR: 54.3% | 29.9 | NR | NCT03048877456 |
| VEGF(R) | a. Chemotherapy + bevacizumab; b. chemotherapy | R/M-SCCHN | 3 | 403 | 40 months | ORR: 35.5% vs. 24.5% | 12.6 vs. 11.0 | 6.0 vs. 4.3 | NCT00588770465 |
| VEGF(R) | RT + PF + bevacizumab | LA-NPC | 2 | 46 | 2.5 years | – | 2-year: 90.9% | 2-year: 83.7% | NCT00408694467 |
| VEGF(R)+ EGFR | cetuximab + bevacizumab | R/M-SCCHN | 2 | 46 | 9.7 months | ORR: 16 | 7.5 | 2.8 | 416 |
| VEGF(R)+ EGFR | a. RT + cetuximab + pemetrexed + bevacizumab; b. RT + cetuximab + pemetrexed | LA-SCCHN | 2 | 78 | 32 months | – | 2-year: 88% | 2-year: 75% vs. 79% | NCT00703976472 |
| PI3K | a. Buparlisib; b. Buparlisib + cetuximab | R/M-SCCHN | 2 | 53 | – | Disease control rate: 49% vs. 91% | 143 vs. 206 days | 63 vs. 111 days | NCT01527877473 |
| PI3K | a. Buparlisib + paclitaxel; b. placebo + paclitaxel | R/M-SCCHN | 2 | 158 | 18.1 months | ORR: 39% vs. 11% | 10.4 vs. 6.5 | 4.6 vs. 3.5 | NCT01852292475 |
| mTOR | Temsirolimus + carboplatin + paclitaxel | R/M-SCCHN | 2 | 39 | – | ORR: 41.7% | 12.8 | 5.9 | 492 |
| c-MET | a. Cabozantinib; b. placebo | Progressive MTC | 3 | 330 | 13.9 months | ORR: 28% vs. 0% | 26.6 vs. 21.1 | 11.2 vs. 4.0 | NCT00704730496,497 |
| c-MET | a. Cabozantinib; b. placebo | Radioiodine-refractory DTC | 3 | 227 | 8.9 months | ORR: 15% vs. 0% | 6-month: 85% vs. 73% | 6-month: 57% vs. 17% | NCT03690388499 |
| RET | Selpercatinib | RET-altered thyroid cancers | 1–2 | 162 | 7.8 months | ORR: 69–79% | – | 1-year: 64–92% | NCT03157128503 |
| RET | a. Vandetanib; b. placebo | LA- or metastatic MTC | 3 | 331 | 24 months | ORR: 45% vs. 13% | – | 6-month: 83% vs. 63% | NCT00410761504 |
RT radiotherapy, MFS metastasis-free survival, HPV human papillomavirus, OPC oropharyngeal cancer, LRF locoregional failure and distant metastasis, EFS event-free survival, TPF taxanes, cisplatin, and 5-FU, ICT induction chemotherapy, LFS laryngectomy-free survival, TPC taxanes, cisplatin, and cetuximab, RTC radiotherapy + cetuximab, PF cisplatin and 5-FU, PCF platinum, cetuximab and 5-FU, LRC locoregional control, R/M-NPC recurrent/metastatic nasopharyngeal carcinoma, NR not reached, MTC medullary thyroid cancer, DTC differentiated thyroid cancer