Genomic profiling of penile squamous cell carcinoma reveals major biomarkers for efficacy of immunotherapy

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Published: 23 Feb 2023
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Prof Andrea Necchi - The Vita-Salute San Raffaele University, Milan, Italy

Prof Andrea Necchi speaks to ecancer about the evaluation of penile squamous cell carcinoma (PSCC) by comprehensive genomic profiling based on tumour mutational burden (TMB) levels that can reveal major biomarkers for the efficacy of immune checkpoint inhibitor (ICPI) therapies.

Tumour mutational burden has emerged as a major biomarker of efficacy in immune checkpoint inhibitor therapies in the neoadjuvant, adjuvant and metastatic disease setting in a wide variety of malignancies, but not in penile squamous cell carcinoma.

Prof Necchi explores the evaluation of PSCC by comprehensive genomic profiling based on tumour mutational burden levels which shows significant differences in biomarkers for the near 15% of cases that have TMB >10 muts/Mb.

The second abstract was about the genomic landscape study for penile squamous cell carcinoma. We looked at the Foundation Medicine database, genomic database, in particular looking at the genomic profile and the mutations and fusions and the gene alterations in general in patients with TMB high level in their tumour.  We know that about less than one third of the patients with penile cancer reveal a high value of TMB and, in fact, these findings were confirmed because about 10% of the patients revealed a TMB between 10-19 muts/Mb and about 4.5%, a bit less than 5%, revealed a high level of TMB, meaning levels equal or higher than 20 muts/Mb.

There were significant differences in the genomic landscape and biology in general between the patient A category and B category in patients. In particular, in cases endowed with high levels of TMB there was a strong association with HPV positivity, so infection by human papilloma virus, and in particular mutations of two genes, the PIK3CA and the KMT2D mutations.

So maybe in the near future we should look at the TMB high, HPV positive, PIK3CA and KMT2D mutated tumours as a distinct category of penile cancer patients towards which design the next generation trials are due in the newer therapies or maybe immune therapy. We do have a well-established label for TMB high tumours by the FDA with pembrolizumab and we do have initial evidence with immunotherapy also in chemorefractory advanced penile cancer patients. So maybe this data may be helpful for the design of the next studies incorporating combinations of immunotherapies.