Table 1. . Summary of completed neoadjuvant immunotherapy and targeted therapy studies.
| Study (Year) | Treatment | Disease stage (n) | Sample size (n) | pPR (%) | pCR (%) | Median follow-up (months) | RFS | OS | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| Immunotherapy | |||||||||
| Tarhini et al. (2014) | Ipilimumab 10 mg/kg | IIIB (3) IIIC (30) IV (2) |
35 | Not reported | 0 | 18 | 10.8 months | Not reported | [18] |
| Blank et al. (2018)† | Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg | III (10) | 10§ | 1 (10%) | 3 (30%) 3 (30%) near pCR |
25.6 | Not reached | Not reached | [20] |
| Amaria et al. (2018) † | Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg | IIIB (3) IIIC (5) IV (3) |
11 | Not reported | 5 (45%) | 15.6 | 82% at 17.2 months | 100% at 24.4 months | [21] |
| Nivolumab 3 mg/kg | IIIB (6) IIIC (5) IV (1) |
12 | Not reported | 3 (25%) | 15 | 58% at 22.6 months | 76% at 22.6 months | ||
| Tarhini et al. (2018 | Ipilimumab 3 or 10 mg/kg High-dose interferon |
IIIB (3) IIIC (25) |
28 | 0‡ | 9 (32%) | 32 | Not reached | Not reported | [19] |
| Tarhini et al. (2018) | Pembrolizumab 200 mg High-dose interferon |
IIIB (5) IIIC (11) IV (4) |
20 | Not reported | 7 (35%) | 11 | Not reported | Not reported | [22] |
| Targeted Therapy | |||||||||
| Sloot et al. (2016) | Vemurafenib 960 mg BID or Dabrafenib 150 mg QD ± Trametinib¶ |
III (15) | 6†† | 2 (33%) | 2 (33%) | 25.4 | Not reported | Not reached | [27] |
| Zippel et al. (2017) | Vemurafenib 960 mg BID or Dabrafenib 150 mg QD ± Trametinib 2 mg QD |
III (13) | 13 | 8 (62%) | 4 (31%) | 20 | Not reported | Not reached | [28] |
| Eroglu et al. (2017) | Vemurafenib¶ Dabrafenib + Trametinib¶ Encorafenib + Binimetinib¶ |
IIIC (9) IV (11) |
20 | Not reported | 7 (35%) | 25 | Not reported | Not reported | [29] |
| Amaria et al. (2018)† | Dabrafenib 150 mg BID Trametinib 2 mg QD |
IIIB (2)‡‡ IIIC (10)‡‡ IV (2)‡‡ |
12‡‡ | 2 (17%) | 7 (58%) | 18.6 | 19.7 months# | Not reached | [31] |
†
Terminated early.
‡
Two patients with minimal residual disease (single cancer cell or minute clumps of cancer cells).
§
Neoadjuvant arm. Of 10 patients, 9 were evaluable for pathologic response
¶
Dose not reported.
#
Median event-free survival.
††
Of 15 patients, only 6 underwent surgery.
‡‡
Of 14 patients, only 12 underwent surgery. One patient withdrew consent prior to initiation of protocol, stage of disease not specified.
OS: Overall survival; pPR: Pathologic partial response; pCR: Pathologic complete response; RFS: Recurrence free survival.