Table 7.
Possible predictors to immune checkpoint inhibitors response in locally advanced and metastatic cutaneous squamous cell carcinoma and basal cell carcinoma.
| Potential Predictor and Its Assessment | Number of Patients and Type of Malignancy | Treatment | Value as Predictor | Ref. |
|---|---|---|---|---|
| Primary tumor location on the head/neck; clinical | 26 advanced cSCCs (5 la-cSCC; 21 m-cSCC) |
Cemiplimab (13 patients), pembrolizumab (7) and nivolumab (6) | Positive predictor (p-value = 0.04) |
In et al., 2020 [42] |
| Primary tumor location on the leg; clinical | 46 advanced cSCCs (25 la-cSCC; 21 m-cSCC) |
Cemiplimab (8), pembrolizumab (28), nivolumab (10) | Negative predictor (p-value = 0.014) | Salzmann et al., 2020 [178] |
| Primary tumor location on the head/neck (A); performance status <2 (B); clinical | 245 advanced cSCCs (85 la-cSCC; 159 m-cSCC, 1 unknown) |
Cemiplimab | Positive predictors: ([A] p-value = 0.0001; [B] p-value = 0.0025) | Hober et al., 2021 [44] |
| Age > 60 years; clinical | 18 advanced cSCCs (13 la-cSCC; 5 m-cSCC) |
Cemiplimab | Positive predictor (p-value = 0.002) | Guillaume et al., 2021 [43] |
| Head/neck tumor location (A); normal haemoglobin values (B); clinical and blood-based | 131 advanced cSCCs (91 la-cSCC; 40 m-cSCC) |
Cemiplimab | Positive predictors: ([A] p-value = 0.007; [B] p-value = 0.034) | Baggi et al., 2021 [45] |
| Tumor location on the genitalia (A), treatment with any systemic antibiotic within 1 month of cemiplimab initiation (B), performance status ≥ 1 (C), chronic corticosteroids therapy (D), previous radiation therapy to lymph nodes (E); previous chemotherapy (F); clinical | 131 advanced cSCCs (91 la-cSCC; 40 m-cSCC) |
Cemiplimab | Negative predictors: ([A] p-value = 0.041; [B] p-value = 0.012; [C] p-value = 0.012; [D] p-value = 0.038; [E] p-value = 0.052; [F] p-value = 0.002) | Baggi et al., 2021 [45] |
| Head/neck tumor location (A); haemoglobin > 12 g/dL (B); clinical and blood-based | 30 advanced cSCCs (25 la-cSCC; 5 m-cSCC) |
Cemiplimab | Positive predictors: ([A] p-value = 0.016; [B] p-value = 0.042) | Strippoli et al., 2021 [51] |
| Absolute lymphocyte count; blood-based | 61 advanced cSCCs (14 la-cSCCs; 47 m-cSCCs) |
Cemiplimab, pembrolizumab, nivolumab | Positive predictor (p-value < 0.01) |
Hanna et al., 2020 [179] |
| Elevated lactate dehydrogenase serum levels; blood-based | 46 advanced cSCCs (25 la-cSCC; 21 m-cSCC) |
Cemiplimab (8), pembrolizumab (28), nivolumab (10) | Negative predictor (p-value = 0.002) | Salzmann et al., 2020 [178] |
| Baseline low neuthophil/lymphocyte ratio + low platelet/lymphocyte ratio; blood-based | 30 advanced cSCCs (25 la-cSCC; 5 m-cSCC) |
Cemiplimab | Positive predictor | Strippoli et al., 2021 [51] |
| PD-L1 expression; immunohistochemical | 48 la-cSCCs | Cemiplimab | Potential positive predictor | Migden et al., 2019 [41] |
| PD-L1 expression; immunohistochemical | 16 advanced BCCs | Pembrolizumab monotherapy (9 patients), pembrolizumab + vismodegib (7) | Not confirmed as predictor | Chang et al., 2019 [75] |
| PD-L1 expression; immunohistochemical | 57 advanced cSCCs (43 locoregional cSCCs and 14 m-cSCCs) |
Pembrolizumab | Positive predictor (p-value = 0.02) |
Maubec et al., 2020 [65] |
| PD-L1 expression; immunohistochemical | 50 la-BCCs | Cemiplimab | Not confirmed as predictor | Stratigos et al., 2021 [12] |
| Low-level CNAs in the 3 q chromosomal arm; molecular biology techniques | 33 advanced cSCC | Anti-PD-1, not specified | Positive predictor (p-value < 0.01) | Kacew et al., 2019 [119] |
| High TMB; molecular biology techniques | 50 la-cSCCs | Cemiplimab | Potential positive predictor | Migden et al., 2019 [41] |
| High TMB; molecular biology techniques | 61 advanced cSCCs (14 la-cSCCs; 47 m-cSCCs) |
Cemiplimab, pembrolizumab, nivolumab | Positive predictor (p-value = 0.02) |
Hanna et al., 2020 [179] |
| High TMB; molecular biology techniques | 26 advanced cSCCs (5 la-cSCC; 21 m-cSCC) |
Cemiplimab (13 patients), pembrolizumab (7) and nivolumab (6) | Positive predictor (p-value = 0.04) |
In et al., 2020 [42] |
Note: Abbreviations: TMB (tumor mutational burden); CNAs (copy-number alterations); la-BCC (locally advanced basal cell carcinoma; la-cSCC (locally advanced cutaneous squamous cell carcinoma); m-cSCC (metastatic cutaneous squamous cell carcinoma).