TKI based therapies of RCC and their clinical trials
| Drug | Trial | Findings of the trial | Reference |
|---|---|---|---|
| Pazopanib | Double blind, randomized, placebo-controlled phase III trial (sample size: 435) | Treatment with pazopanib significantly prolonged median PFS in comparison to placebo (9.2 months vs. 4.2 months; HR = 0.46, P < 0.001) in patients with locally advanced or metastasised RCC | [97] |
| Cabozantinib | The Alliance A031203 CABOSUN trial | Monotherapy with 60 mg of daily cabozantinib compared to sunitinib standard therapy (50 mg once per day; 4 weeks on, 2 weeks off) resulted in an increased ORR (33% vs. 12%) and a remarkable PFS benefit (8.2 months vs. 5.6 months) | [99] |
| Sorafenib | TARGET trial (sample size: 903) | Sorafenib displayed superiority as indicated by the median PFS (5.5 months vs. 2.8 months) in the placebo group with an HR of 0.44 (P < 0.01) | [100, 101] |
| Tivo-1 trial | Compared to tivozanib, sorafenib therapy displayed worse PFS but similar OS | ||
| Axitinib | Phase-3 AXIS trial (sample size: 723) | In comparison to sorafenib, median PFS was significantly longer in metastasised RCC patients treated with axitinib (8.3 months vs. 5.7 months, HR = 0.66, P < 0.0001) As evident with fewer AE-related treatment discontinuation, axitinib was unique due to less severe side effects | [102] |
| Phase II AXIPAP trial | The overall median PFS, median PFS for type 1 pRCC, and median PFS for type 2 pRCC were 6.6 months, 6.7 months, and 6.2 months, respectively The median overall OS was 18.9 months Type 2 pRCC showed a rather high 36% ORR | [103] | |
| Cabozantinib vs. Sunitinib | SWOG PAPMET trial | Cabozantinib displayed a PFS benefit (9.0 months vs. 5.6 months; HR = 0.60) and higher ORR (23% vs. 4%) over sunitinib | [104] |
| Pembrolizumab + lenvatinib vs. sunitinib | CLEAR trial | Pembrolizumab + lenvatinb demonstrated a longer median PFS (23.9 months vs. 9.2 months; HR = 0.39) over sunitinib Pembrolizumab + lenvatinib-treated patients had improved OS and higher ORR (71.0% vs. 36.1%) over sunitinib-treated patients The risk of death observed was 34% lower in patients treated with pembrolizumab + lenvatinib | [101] |
| Lenvatinib/everolimus vs. lenvatinib + everolimus | Phase-II trial | A longer PFS was observed for longer PFS for lenvatinib and everolimus in combination and single agent lenvatinib when compared to everolimus, respectively The longest median PFS of 14.6 months was obtained with combinational therapy of lenvatinib and everolimus Lenvatinib monotherapy displayed a PFS of 7.4 months and a hazard ratio of 0.66 Severe AE was observed in 71% and 79% of those receiving lenvatinib combination- and single-agent-therapy, respectively | [105] |
| Atezolizumab + bevacizumab vs. sunitinib | Phase III IMmotion151 trial | Patients receiving atezolizumab + bevacizumab, reported greater symptom improvements vs. sunitinib with an objective response of 49% vs. 14%, including complete responses of 10% vs. 3% | [102] |
| Cabozantinib and nivolumab vs. sunitinib | CheckMate 9ER trial | A better OS rate, PFS, and a more likely response than sunitinib monotherapy was demonstrated with a combination of cabozantinib and nivolumab | [106] |
PFS: progression free survival; HR: hazard ratio; ORR: objective response rate; AE: adverse events
