TABLE 2.
Studies evaluating adjuvant therapy, immunotherapy, and/or targeted therapy for cSCC during the last 10 years
| Studya | Study type | Multi‐ or single‐site | No. of patients | Cohort characteristics | Findings |
|---|---|---|---|---|---|
| Improvement with ART | |||||
| Stevenson et al.62 | Retrospective | Single | 31 | cSCC with negative surgical margins and PNI | Patients receiving MMS plus ART did not develop nodal metastasis, while all patients who developed nodal metastasis had MMS without ART (p = 0.02). Five‐year DFS was significantly higher for patients having MMS plus ART vs. MMS alone (p = 0.01) |
| Miller et al.63 | Retrospective | Single | 32 | cSCC with negative surgical margins | Surgical resection plus ART for BWH T2b‐T3 tumors resulted in DFS for 91% of patients at last f/u or death |
| Harris et al.64 | Retrospective | Multi | 349 | Advanced HNcSCC | OS and DFS were improved with surgery plus ART compared to surgery alone in patients with HNcSCC with PNI and/or regional disease |
| Coombs et al.65 | Retrospective | Single | 63 | HNcSCC with metastasis to parotid gland | Patients receiving surgery plus ART had significantly higher 5‐year DFS compared with patients treated with surgery alone (84% vs. 48%, respectively, p = 0.008) |
| Sapir et al.66 | Retrospective | Single | 30 | HNcSCC with extensive PNI | Patients receiving surgery plus ART had significantly higher DFS compared with patients receiving surgery and observation only (73% vs. 40%, respectively, p = 0.05) |
| Kadakia et al.67 | Retrospective | Single | 53 | HNcSCC of scalp, immune compromised | Patients receiving surgery plus ART had higher 3‐year DFS and OS compared with patients receiving surgery alone (80% and 62% vs. 62.5% and 37.5%, respectively) |
| Wray et al.68 | Retrospective | Single | 71 | cSCC of face, ears, and scalp | Elective ART to sentinel LNs in high‐risk cSCC of the face, ears, and scalp provided regional control for 96% of patients at 5 years post‐treatment, with 0% developing grade 3+ toxicity (patients had no previous regional LN surgery or evidence of LN metastasis) |
| Wang et al.69 | Retrospective | Single | 122 | HNcSCC with cervical LN involvement | Surgery alone was compared with surgery plus ART; 55% compared with 23% of patients developed recurrence, respectively. DFS and OS were significantly improved with surgery plus ART (p = 0.001 and p = 0.003, respectively). Improved DFS was significantly associated with no ECE |
| Givi et al.70 | Retrospective | Single | 51 | HNcSCC with metastasis to LNs of head and neck | Surgery alone was compared with surgery plus ART; OS was significantly improved with ART (p = 0.002) |
| Strassen et al.73 | Retrospective | Single | 67 | Recurrent HNcSCC | Patients who received ART had significantly higher 5‐year RFS and OS rates compared with patients who did not receive ART (p = 0.02 and p < 0.05) |
| No improvement with ART or ACRT | |||||
| Ruiz et al.75 | Retrospective | Single | 62 | cSCC with negative surgical margins, LN‐negative | Surgery alone was compared to surgery plus ART; no significant differences were found in local recurrence, metastasis, or DSD rates |
| Trosman et al.76 | Retrospective | Single | 104 | Advanced HNcSCC | Surgery alone was compared to surgery plus ART or plus ACRT; no significant differences were found in 2‐year DFS |
| Amoils et al.77 | Retrospective | Single | 80 | HNcSCC with metastasis to LNs | Surgery alone was compared to surgery plus ART or plus ACRT; no significant differences were found in 3‐year OS. Decreased OS was significantly associated with primary tumor >2 cm and ECE (p = 0.03 and p = 0.01, respectively) |
| Improvement with ACRT versus ART | |||||
| Tanvetyanon et al.86 | Retrospective | Single | 61 | High‐risk HNcSCC with metastasis to LNs (≥2 LNs), ECE, or positive margins | ACRT was compared to ART alone (no comparisons to surgery alone were reported). Median RFS was higher for patients given ACRT versus patients given ART (40.3 versus 15.4 months, respectively); risk of recurrence was significantly reduced with ACRT (HR 0.31, p = 0.01) |
| No improvement with ACRT versus ART | |||||
| Porceddu et al.82 | Prospective, phase III | Multi | 321 | Advanced HNcSCC | When ART was compared to ACRT (no comparisons to surgery alone were reported), no significant differences were found in DFS or OS. 2‐ and 5‐year FFLRR rates were 88% and 83% for ART and 89% and 87% for ACRT, respectively. Carboplatin did not enhance ART toxicity |
| No improvement with adjuvant chemotherapy or targeted therapy plus ART versus ART | |||||
| Goyal et al.91 | Retrospective | Single | 32 | Locally advanced HNcSCC | Systemic therapy (chemotherapy or targeted therapy) given concurrently with ART was compared to ART alone (no comparisons to surgery alone were reported). No significant differences were found in LRC, DC, or PFS. Median OS was significantly lower and risk of death was significantly higher for patients treated with systemic therapy plus ART (p = 0.03 and p = 0.04, respectively) |
| Improvement with immunotherapy or targeted therapy | |||||
| Migden et al.98 | Prospective, phase II | Multi | 78 | Locally advanced cSCC without metastasis | Single‐arm study of cemiplimab (3 mg/kg every 2 weeks) demonstrated an objective (complete or partial) response in 44% of the cohort; 13% complete and 31% partial response. Hypertension (8%) and pneumonia (5%) were the most common AEs |
| Migden et al.94 | Prospective, phase II | Multi | 59 | Metastatic cSCC | Metastatic disease cohort to determine tumor response, clinical benefit (OS and PFS), and duration of response to cemiplimab (3 mg/kg every 2 weeks). Tumor response was 47% and durable DC was 61% of the cohort. Diarrhea (27%) and fatigue (24%) were the most common AEs in the cohort |
| Prospective, phase I | Multi | 26 | Locally advanced or metastatic cSCC | Expansion cohort to determine tumor response, safety, and side‐effect profile of cemiplimab (3 mg/kg every 2 weeks). Tumor response was 50%, durable DC was 65%, and fatigue was the most common AE in 27% of the cohort | |
| Rischin et al.110 | Prospective, phase II | Multi | 115 | Metastatic cSCC | Cemiplimab produced substantial antitumor activity and durable response with acceptable safety profiles in weight‐based (3 mg/kg every 2 weeks) and fixed (350 mg every 3 weeks) dosing cohorts with metastatic cSCC |
| Gross et al.111 | Prospective, phase II | Multi | 20 | Locally advanced or metastatic cSCC | Neoadjuvant cemiplimab was well tolerated in stage III/IV (M0) (AJCC8) HNcSCC, with ORR of 30% and pathologic complete response and major pathology response rates of 55% and 15%, respectively |
| Grob et al.112 | Prospective, phase II | Multi | 105 | Locally recurrent and/or metastatic cSCC | R/M cohort to determine efficacy and safety of pembrolizumab. ORR was 34%, DC was 52%, median PFS was 6.9 months, and median response duration (range, 2.7–13.1+) and median OS were not reached. Common AEs were fatigue, asthenia, pruritus, pain, diarrhea, nausea |
| Maubec et al.104 | Prospective, phase II | Multi | 36 | Locally advanced or metastatic cSCC | EGFR inhibitor (cetuximab) studied in unresectable cohort to evaluate efficacy and safety. DC was 69% at 6 weeks. AEs were acne‐like rash (grade 1–2) in 78% of patients, and grade 3–4 reactions in three patients; no AE‐related deaths. OS was 8.1 months, median PFS was 4.1 months |
| Lewis et al.105 | Prospective, phase II | Single | 22 | Aggressive or recurrent cSCC | EGFR inhibitor (gefitinib) studied in the neoadjuvant and adjuvant setting to determine response rate (45.5% overall to neoadjuvant induction); 2‐year OS (72.1%), DSS (72.1%), and PFS (63.6%; and toxicity (grade 1–3). Diarrhea, fatigue, rash, and nausea were the most common AEs. Study was terminated after first stage due to progressive disease rate (31.7%) |
Abbreviations: ACRT, adjuvant chemotherapy plus adjuvant radiation therapy (adjuvant chemoradiotherapy); AE, adverse event; AEs, adverse events; AJCC8, American Joint Committee on Cancer Staging Manual, Eighth Edition; ART, adjuvant radiation therapy; BWH, Brigham and Women's Hospital; cSCC, cutaneous squamous cell carcinoma; DC, disease control; DFS, disease‐free survival; DSD, disease‐specific death; DSS, disease‐specific survival; ECE, extracapsular extension (or spread, also known as extranodal extension [ENE]); EGFR, epidermal growth factor receptor; FFLRR, freedom from locoregional relapse; f/u, follow‐up; HNcSCC, cSCC of the head and neck; LN, lymph node; LNs, lymph nodes; LRC, local regional control; MMS, Mohs micrographic surgery; ORR, objective response rate; OS, overall survival; PFS, progression‐free survival; PNI, perineural invasion; RFS, recurrence‐free survival; R/M, recurrent and/or metastatic.
a
The studies are listed in order of mention in the text and by outcome findings per treatment modality.