Table 4.
Summary of the other tyrosine kinase anti-angiogenesis inhibitors clinical trials for head and neck squamous cell carcinoma.
| Reference, clinical trial | Intervention | Phase | Completion year, Country | Treatment line | No. of patients | Follow-up | Evaluation criteria | CR | PR | ORR | SD | PD | DCR | OS | PFS | Conclusion |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 12 | Lenvatinib in combination with pembrolizumab | N/A | NA, Taiwan | Second or more | n = 14 | Median 2.8 months | RECIST 1.1 | 0.0% (n = 0) | 28.6% (n = 4) | 28.6% (n = 4) | 14.3% (n = 2) | 57.1% (n = 8) | 42.9% (n = 6) | Median 6.2 months | Median 4.6 months | “Our study provided up-to-date evidence that pembrolizumab/lenvatinib combination therapy achieved objective responses in both heavily pretreated and anti-PD-1 refractory R/M HNSCC patients. This study supported the use of pembrolizumab/lenvatinib combination therapy in R/M HNSCC patients without standard of care.” |
| (95% CI 5.0-52.2) | (95% CI 17.0-68.8) | (95% CI 2.9-9.6) | (95% CI 0.05-9.2) | |||||||||||||
| 13 | Lenvatinib in combination with pembrolizumab | Ib/II | 2018, USA | First, second or more | n = 22 | N/A | RECIST | 5% (n = 1) | 41% (n = 9) | 46% | 46% (n = 10) | 0% (n = 0) | N/A | N/A | Median 4.7 months | “Lenvatinib plus pembrolizumab demonstrated a manageable safety profile and promising antitumor activity in patients with selected solid tumor types.” |
| NCT02501096 | 95% CI 24.4-67.8) | (95% CI 4.0-9.8) | ||||||||||||||
| 47 | I | 2009, USA | First | Total: n = 33 | Median 19.8 months | RECIST 1.0 | N/A | N/A | N/A | 1-year OS | 1-year OS | “Vandetanib with CRT was feasible.” | ||||
| NCT00450138 | Evaluated pateints: n = 30 | 96.9% (95% CI 91-100) | 96.9% (95% CI 91-100) | |||||||||||||
| Regimen 1: Vandetanib with radiotherapy | Regimen 1: n = 12 | Regimen 1: 92% | Regimen 1: Vandetanib 100mg: 100.0% | Regimen 1: Vandetanib 100mg: 100.0% | ||||||||||||
| Vandetanib 200mg: 100.0% | Vandetanib 200mg: 100.0% | |||||||||||||||
| Regimen 2: Vandetanib with radiotherapy and cisplatin | Regimen 2: n = 18 | Regimen 2: 100% | Regimen 2: Vandetanib 100mg: 86.7% | Regimen 2: Vandetanib 100mg: 86.7% | ||||||||||||
| Vandetanib 200mg: 66.7% | Vandetanib 200mg: 66.7% | |||||||||||||||
| 48 | Control group: Docetaxel | II | 2009, USA | Second | Total: n = 29 | N/A | RECIST | Control group: 0% | Control group: 7% (n = 1) | Control group: 7% (n = 1) | Control group: 21% (n = 3) | Control group: 50% (n = 7) | Control group: 28.6% (n = 4) | Median weeks | Median weeks | “Although an initial benefit in response was noted and statistical criteria met there was only a minor trend towards improved PFS for the combined arm. The study was designed with low threshold for activity in each arm and results were deemed not to be of enough clinical significance in this group of patients to continue accrual.” |
| Control group: n = 14 | Control group: 26.8 | Control group: 3.21 | ||||||||||||||
| (95% CI 0.2-33.8%) | (95% CI 17.7-100.7) | (95% CI 3.0–22.0) | ||||||||||||||
| Vandetanib group: Vandetanib with docetaxel | Vandetanib group: n = 15 | Vandeta-nib group: 0% | Vandeta-nib group: 13% (n = 2) | Vandeta-nib group: 13% (n = 2) | Vandeta-nib group: 47% (n = 7) | Vandeta-nib group: 33% (n = 5) | Vandeta-nib group: 60% (n = 9) | Vandeta-nib group: 24.1 | Vandeta-nib group: 9 | |||||||
| (95% CI 1.6-40.4%) | (95% CI 16.4-171.1) | (95% CI (5.86–18.1) | ||||||||||||||
| 49 | Axitinib monotherapy | II | 2015, China | Second or more | Total: n = 40 | Median 28.3 months | RECIST 1.0 | N/A | n = 1 | N/A | n = 22 | N/A | N/A | Median 10.4 months | Median 5.0 months | “Axitinib achieved durable disease control with a favorable safety profile in heavily pretreated NPC patients.” |
| Evaluated patients: n = 37 | (95% CI 6.8-19.0) | (95% CI 3.9-5.7) | ||||||||||||||
| 1-year OS | ||||||||||||||||
| 46.3% | ||||||||||||||||
| 50 | Axitinib monotherapy | II | N/A, USA | Second or more | n = 30 | N/A | RECIST 1.0 | 0% | 7% (n = 2) | 7% (n = 2) | 70% (n = 21) | 23.3% (n = 7) | 76.7% (n = 23) | Median 10.9 months | Median 3.7 months | “Treatment with single agent axitinib should be considered due to acceptable toxicity profile and favorable median overall survival compared to standard therapies.” |
| (95% CI 6.4-17.8) | (95% CI 3.5-5.7) | |||||||||||||||
| 51 | Pazopanib daily with cetuximab weekly | I | 2017, USA | Second | n = 31 | Median 9.5 months | RECIST 1.1 | 6% (n = 2) | 29% (n = 9) | 35% (n = 11) | 45% (n = 14) | 19% (n = 6) | N/A | Median 9.5 months (95% CI 8.1-13.9) | N/A | “Pazopanib oral suspension at a dose of 800 mg/day was feasible to administer in combination with standard weekly cetuximab for patients with recurrent or metastatic HNSCC. Encouraging preliminary antitumour activity was observed with this combination therapy and warrants further validation in randomised trials.” |
| 52 | Pazopanib monotherapy | II | 2009, Singa-pore | Second or more | n = 33 | N/A | RECIST | 0% | 6.1% (n = 2) | N/A | 48.5% (n = 16) | 33.3% (n = 11) | N/A | Median 10.8 months | 1-year PFS | “Pazopanib showed encouraging activity in heavily pretreated nasopharyngeal carcinoma with an acceptable toxicity profile.” |
| (95% CI 8.6-21.8) | 13% | |||||||||||||||
| 1-year OS | ||||||||||||||||
| 44.4% | ||||||||||||||||
| 53, NCT01462474 | Famitinib with concurrent chemoradio-therapy (cisplatin) | I | 2016, China | First | n = 20 | Median 44 months | RECIST 1.1 | CR after comple-tion of CCRT: 65.0% (n = 13) | PR in famitinib mono-therapy: 15% (n = 3) | N/A | SD in famitinib mono-therapy: 80% (n = 16) | PD in famitinib mono-therapy: 5% (n = 1) | N/A | N/A | 1-year | “The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC. Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy.” |
| PFS 85% | ||||||||||||||||
| 2-year | ||||||||||||||||
| PFS 70% | ||||||||||||||||
| 3-year PFS | ||||||||||||||||
| 70% | ||||||||||||||||
| PR after completion of CCRT: 35.0% (n = 7) | ||||||||||||||||
| 54 | Foretinib montherapy | II | 2009, USA | Second | n = 14 | Patients were contact-ed for follow-up at 90 and 180 days after the last dose. | RECIST 1.0 | 0% | 0% | 0% | n = 7 | n = 3 | n = 7 | Median 5.59 months | Median 3,65 months | “The efficacy results, prolonged disease stabilization and tolerable side-effect profile, support further investigation, possibly in combination with other targeted agents or cytotoxic chemotherapy for SCCHN.” |
| (95% CI 0-23.2) | 50% | 24.1% | 50% | |||||||||||||
| (95% CI 23.0–77.0) | (95% CI 3.71 - NA) | (95% CI 3.4-5.3) | ||||||||||||||
| 55 | m-510 with gemcitabine and cisplatin | I | 2003, Nether-lands | Third or more | n = 13 | N/A | N/A | N/A | n = 3 | N/A | n = 8 | N/A | N/A | N/A | N/A | “Combining ABT-510 at doses of 50 mg and 100 mg with gemcitabine–cisplatin is feasible.” |
CCRT, concurrent chemoradiotherapy; CDR, disease control rate; CI, confidence interval; CR, complete response rate; CRT, chemoradiation; HNSCC, head and neck squamous cell carcinoma; HR, hazard ratio; N/A, not available; NPC, nasopharyngeal carcinoma; ORR, overall response rate; OS, overall survival; PD, progressive disease; PD-1, programmed cell death protein; 1 PFS, progression free survival; PR. partial response rate; RECIST, Response Evaluation Criteria in Solid Tumours; SD, stable disease; WHO, World Health Organization criteria.