Penile cancer is a rare GU tumour in developed countries, although in developing countries it makes up 10% of male cancers. Recently immune checkpoint inhibitors have been approved for different cancer types and we’re really interested in knowing how do immune checkpoint inhibitors work in patients with penile cancer. That’s how we started our study regarding penile cancer.
The reason we wanted to investigate immune checkpoint inhibitors in penile cancer is because we know that tumours of penile cancers, the tumour cells would have PD-L1 expression. We know that the tumours are infiltrated with lymphocytes and we know that there is a high percentage of HPV infection as well – 30-50% in this case – and we know that immune checkpoint inhibitors work in HPV infected tumours. Thus, really we are interested in the outcomes of patients with penile cancer. So what we did is we reached out to 24 institutions as part of the Global Society of Rare GU Tumours and we collected data, baseline data, on the patients and we looked at the overall survival, the progression free survival and the overall response rate.
Key findings – we had 92 patients in our cohort, 90% of the patients had metastatic disease meaning it was metastatic to distant organs or distant lymph nodes. 80% of the patients received immune checkpoint inhibitors in the second line setting or beyond. Looking at the clinical outcomes, the median overall survival was 9.8 months in the overall cohort; the median progression free survival was 3.2 months in the overall cohort and the overall response rate was 13%. Examining different potential biomarkers we looked at HPV status, we looked at neutrophil-to-lymphocyte ratio and presence of visceral metastases. We did not see differences in outcomes for patients with HPV or without HPV infection in the tumour. What we saw is that patients who had a high neutrophil-to-lymphocyte ratio and presence of visceral metastases, those patients tended to do worse than patients who had a lower neutrophil-to-lymphocyte ratio and did not have visceral metastases.
As for the safety outcomes, 29% of the patients in our cohort developed treatment related adverse events and when we broke down the treatment related adverse events by type of therapy the patients who received single immune checkpoint inhibitor had 21% treatment related adverse events versus 31% in patients who received dual immune checkpoint inhibitor – anti-PD-1 plus anti-CTLA-4. That number went up to 75% in patients who received anti-PD-1 and anti-CTLA-4 plus a targeted therapy with a TKI. Thus, we saw minimal activity across all three groups but that was a clear message to us that combination therapies, although might be promising, we should be careful for the toxicities that they may have on the patients.
The direct impact of this study is at least when a patient with penile cancer walks to the clinic and presents and there is a discussion about immune checkpoint inhibitors, the patient and the oncologist now know what to expect in terms of outcomes. That would guide the treatment selection in the clinic, that’s the direct impact. Another impact would be our study is generating hypotheses for scientists and physician scientists to explore more a translational component and to understand why certain patients respond to therapy and why certain patients do not so that we can guide treatment selection.
The overall message is that penile cancer is a very rare GU tumour, at least in developed countries, and the key in understanding rare GU tumours like penile cancer is collaborations with other centres. In this study we leveraged the Global Society of Rare GU Tumours consortium and we invited other centres to participate in this consortium so that we can generate as much as possible meaningful information for the patients with penile cancer.
Just to close, the key finding is that there are a few patients who respond to immune checkpoint inhibitors. We should be careful in treatment selection and combination therapies, although active, we should be careful with the safety profiles that might be generated.