Table 1.
Clinical trials in perioperative RCC.
| Identifier, year | Phase | Adjuvant/neoadjuvant | N | Intervention arm | Control arm | Primary outcome | Efficacy/dose modifications | Treatment discontinuation rate |
|---|---|---|---|---|---|---|---|---|
| Neoadjuvant/adjuvant trials using single-agent ICI in RCC | ||||||||
| Gorin et al.
13
NCT02575222 |
I, Single arm | Neoadjuvant | 17 | Neoadjuvant nivolumab prior to nephrectomy | Single-arm study | Study met primary outcome of safety and tolerability | MFS: 85.1%; OS: 100% at 2 years | 0% |
| Carlo et al. 12 | II, Single arm | Neoadjuvant | 18 | Neoadjuvant nivolumab prior to nephrectomy | Single-arm study | Met primary outcome of safety and feasibility | — | 2 (11%) |
| Allaf et al.10,17
NCT03055013, 2017 |
III, RCT | Neoadjuvant and adjuvant | 766 | Neoadjuvant and adjuvant nivolumab with nephrectomy | Surgery alone | Did not meet primary outcome of improvement in EFS | No dose modifications to date | 48 (11%) patients in Nivo arm and 50 (12%) patients in surgery alone arm |
| Pal et al.
23
NCT03024996 |
III, RCT | Adjuvant | 778 | Adjuvant atezolizumab | Adjuvant placebo | Did not meet primary outcome of improvement in DFS | No improved clinical outcomes versus placebo | 135(34%) patients in Atezo group and 109 (28%) patients in placebo group |
| Powels et al.
27
NCT03142334 |
III, RCT | Adjuvant | 994 | Adjuvant pembrolizumab | Adjuvant Placebo | Met primary end point of improvement in DFS | Disease recurrence significantly (32%) lower compared to placebo | 190 (38%) patients in pembro group and 130 (26%) in placebo group |
| Neoadjuvant/adjuvant trials using ICI combinations in localized RCC | ||||||||
| Karam
18
NCT03680521 |
II, Single arm | Neoadjuvant | 25 | Neoadjuvant sitravatinib and nivolumab | Single-arm study | Met primary end point of point in time objective response | Dose decreased from 120 mg QD to 80 mg QD due to toxicities | 6 (30%) |
| Bex et al.
19
NCT03341845 |
II, Single arm | Neoadjuvant | 40 | Neoadjuvant axitinib and avelumab | Single-arm study | Met primary outcome of in number of patients with partial remission | Median DFS and OS are not reached | 0% |
| Ornstein et al.
33
NCT02762006 |
Ib, Single-arm study | Perioperative | 29 | Perioperative durvalumab + or − tremelimumab | Single-arm study | Met primary outcome of safety and feasibility | No dose modifications and it is a feasible combination | 1 (17%) in cohort 1, 0% in cohort 2, 3 (38%) in cohort 2a, and 5 (56%) in cohort 3 |
| Bex et al.
35
NCT03138512 |
III, RCT | Adjuvant | 1641 | Adjuvant nivolumab, plus ipilimumab | Nivolumab plus placebo | Did not meet primary end point of improvement in DFS | Disease-free survival was not met at 37 months of median follow-up | 173 (43%) patients in IPI + Nivo group and 46 (11%) patients in Nivo + placebo group |
DFS, disease-free survival; EFS, event-free survival; ICI, immune check point inhibitor; MFS, metastasis-free survival; N, number of patients; OS, overall survival; RCC, renal cell carcinoma; RCT, randomized control trial.