Nivolumab for locally advanced and metastatic cutaneous squamous cell carcinoma (NIVOSQUACS study) - phase II data covering impact of concomitant hematological malignancies

BACKGROUND: Monoclonal antibodies against the programmed death receptor (PD)-1 such as cemiplimab and pembrolizumab have become the current standard of care and first line treatment of advanced cSCC, proving remarkable clinical benefit and acceptable safety.

OBJECTIVES: To assess efficacy and safety of the anti-PD-1 antibody nivolumab in patients with locally advanced and metastatic cSCC.

METHODS: Patients received open-label nivolumab 240 mg intravenously every 2 weeks for up to 24 months. Patients with concomitant hematological malignancies (CHM), either non-progressing or stable under active therapy, were eligible for inclusion.

RESULTS: Of 31 patients with a median age of 80 years, 22.6% of patients achieved an investigator assessed complete response, resulting in an objective response rate (ORR) of 61.3% and a disease control rate (DCR) of 54.4%. Progression free survival (PFS) was 11.1 months, and the median overall survival (OS) was not reached after 24 weeks of therapy. Median follow-up was 23.82 months. Subgroup analysis of the CHM cohort (n = 11; 35%) revealed an ORR of 45.5%, a DCR of 64.5%, a median PFS of 10.9 months, and median OS of 20.7 months. Treatment related adverse events were reported in 58.1% of all patients (19.4% grade 3, the remaining grade 1 or 2). PD-L1 expression and CD-8+ T-cell infiltration did not significantly correlate with clinical response, although a trend towards a shorter PFS of 5.6 months was observed with PD-L1 negativity and low CD8+ intratumoral infiltration.

CONCLUSION: This study demonstrated robust clinical efficacy of nivolumab in patients with locally advanced and metastatic cSCCs and a tolerability comparable to data of other anti-PD-1 antibodies. Favourable outcomes were obtained despite involving the oldest hitherto reported study cohort for anti-PD-1 antibodies and a significant proportion of CHM patients prone to high risk tumors and an aggressive course otherwise typically excluded from clinical trials.