At the ESMO Virtual Congress 2020, very promising efficacy was reported for the use of PD-1 inhibitors in some difficult-to-treat advanced non-melanoma skin cancers (NMSCs), suggesting that immunotherapy may represent a new option for malignancies where there is no approved systemic therapy.
In the KAPKEY trial, pembrolizumab showed a best overall response rate of >30% in patients requiring systemic treatment for extensive ‘classic’ or ‘endemic’ Kaposi Sarcoma (KS)—subtypes of KS that have poorly-defined systemic treatment options (Abstract 1077MO). Of 17 patients enrolled in this first prospective trial, 12 achieved either a complete response (n=2) or partial response (n=10). In the study, 65% and 18% of patients had previously received chemotherapy or interferon-alpha, respectively.
“These data are very important as there is currently no approved systemic therapy for classic/endemic KS,” says Dr Alona Zer from Tel Aviv University, Israel. “Patients with advanced tumours are commonly treated with interferon or chemotherapy. However, response durations tend to be short, and chemotherapy is associated with significant toxicity.”
NMSCs comprise a wide range of cutaneous tumours, whose overall prevalence and incidence—and consequently healthcare burden—are increasing worldwide. KS is a rare NMSC causatively associated with human herpes virus 8 infection, more frequently afflicting individuals with immunodeficiencies. Classic KS typically occurs in people of Mediterranean or Jewish descent, while endemic KS is associated with individuals from sub-Saharan Africa. “Given the viral nature of KS and that it is likely to be driven by the immunogenicity of virus-associated antigens, it is perhaps unsurprising that checkpoint inhibitors are effective,” comments Zer. PD-1 inhibitors have been shown to be effective in Merkel cell carcinoma, another viral-induced NMSC in previous studies. “However, due to the rarity of the disease, there have been only a few prospective trials of immunotherapy agents in classic/endemic KS and more data are needed in this area. KAPKEY provides additional information supporting PD-1 blockade following preliminary promising results last year from a phase II trial of the PD-1 inhibitor, nivolumab, in combination with ipilimumab in classic KS.”
In addition to the biological rationale for efficacy, pembrolizumab also presents an attractive therapeutic consideration due to its relatively better toxicity profile compared with chemotherapy. In KAPKEY, pembrolizumab showed acceptable toxicity, with 71% of patients experiencing a treatment-related side effect and only one grade 3 event. “Classic KS tends to affect elderly men who may find it difficult to tolerate chemotherapy, and less toxic treatment options are needed,” says Zer. “If the promising efficacy and acceptable safety profile are confirmed in further studies, pembrolizumab could become a new standard of care in this setting.”
In order for that to become a reality in clinical practice, Zer feels it is important to have prognostic biomarkers to inform patient selection. In KAPKEY, patients without PD-L1 expression or those with lower germline HLA-1 evolutionary divergence for HLA-B had poorer response to pembrolizumab. Further studies are needed to confirm whether these markers are truly prognostic, cautions Zer, particularly as PD-1 and PD-L1 expression appear to vary according to tumour stage in KS.
PD-1 blockade may also prove an effective treatment option for some patients with advanced basal cell carcinoma (BCC)—which accounts for the majority of NMSCs—according to Late-Breaking data from a phase II trial presented at ESMO Virtual Congress 2020 (Abstract LBA47). Cemiplimab—a PD-1 inhibitor that is already approved for the treatment of advanced cutaneous squamous cell carcinomas—demonstrated clinically meaningful anti-tumour activity, with an overall response rate of 31% and estimated 12-month duration of response among responders of 85%, in patients with locally advanced BCC who had progressed on, or were intolerant to, standard therapy with hedgehog inhibitors.
Abstracts and sessions details
- Stratigos AJ, et al. Primary analysis of Phase 2 results for cemiplimab in patients (pts) with locally advanced basal cell carcinoma (laBCC) who progress on or are intolerant to hedgehog inhibitors (HHIs). ESMO Virtual Congress 2020, Abstract LBA47
Mini Oral – Melanoma and other skin tumours, 18.09.20-20 - Delyon J, et al. PD1 blockade with pembrolizumab in classic and endemic Kaposi sarcoma: A multicenter phase II study. ESMO Virtual Congress 2020, Abstract 1077MO
Mini Oral – Melanoma and other skin tumours, 18.09.20-20
