Srikala Sridhar, MD, Princess Margaret Cancer Centre, Toronto, Canada, discusses results from the phase 2 ALPACA study evaluating avelumab in patients with locally advanced or metastatic penile cancer who were unfit for or experienced disease progression after platinum-based chemotherapy.

Results demonstrated that avelumab was well tolerated and achieved durable responses in a subset of patients, despite modest overall response and survival outcomes. These findings underscore the safety of immune checkpoint blockade in this rare and aggressive cancer and highlight the need for further research and collaborative efforts to improve treatment options.

These results were presented at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.

Transcript:

My name is Dr Srikala Sridhar, I'm a medical oncologist at the Princess Margaret Cancer Centre in Toronto. At this year’s ESMO, I was very pleased to present our abstract entitled ALPACA. This study was essentially looking at avelumab in locally advanced or metastatic penile cancer in patients who were unfit for platinum-based chemotherapy or had progressed on or after platinum-based chemotherapy.

By way of background, we know that penile cancer is a rare and aggressive malignancy that will account for about 38,000 new cases per year worldwide. There is significant geographic variability, but it is found most commonly in Latin America, Africa, and India, and this is largely due to sociodemographic factors. Up to 50% are human papillomavirus (HPV)-related, and 30% to 60% express PD-L1. For patients with metastatic disease, median survival remains less than 1 year. The standard of care in the frontline setting is platinum-based chemotherapy, but this has limited efficacy with objective response rates of about 30% to 40%, low durability, and a progression-free survival of about 3 months or so, and it is poorly tolerated. There are no standard second-line options, which really highlights a significant unmet need in this disease. 

We know that immune checkpoint inhibitors have shown activity in other HPV-related cancers and are generally well tolerated so we embarked on this investigator-initiated, multicenter, single-arm, phase 2 study to determine the efficacy and tolerability of the PD-L1 inhibitor avelumab in patients with penile cancer refractory to or unfit for platinum-based chemotherapy.

This was a multicenter, single-arm phase 2 study, we accrued patients with locally advanced or metastatic penile cancer who were refractory to or unfit for platinum-based chemotherapy. They had to have an ECOG performance status of 0 to 2 and no prior exposure to immune checkpoint inhibitors. They went on to receive avelumab at 10 mg/kg IV every two weeks until toxicity or progression. Tumor assessments were performed every 8 weeks. The primary end point was objective response rate by the investigator using the RECIST criteria. Secondary end points included progression-free survival, overall survival, safety, and tolerability as well as a number of correlative end points. The accrual period was from August 2018 to January 2025, and during this period, we accrued a total of 25 patients however, 23 patients were evaluable, and those are the 23 on whom I reported at ESMO.

When we looked at the key demographic and baseline characteristics, we found the median age of this patient population was 58 years, with 30% having an ECOG performance status of 2, which means this patient population was quite unwell. The majority had visceral metastases, and all but 1 had prior platinum-based chemotherapy. We did check the HPV status, which was available on about half of the patients, and in those, about half were HPV positive. The primary end point was objective response rate by the investigator. Four patients showed a partial response out of a total of 23, giving us an objective response rate of 17%. One additional patient had stable disease, and the disease control rate was 21%. Notably, among patients who were responding, the median duration of response was 15.9 months, with a range of 14 to 16.2 months. 

When we look at the secondary outcomes, with a median follow-up of 15 months, we found the median progression-free survival was 1.7 months, and median overall survival was 3.9 months. On average, patients completed about 3 cycles of treatment. Three patients remain on treatment; 20 patients have come off, of which 19 came off due to disease progression or death.

We did look at a number of correlative studies, including the correlation between HPV status and outcomes. We did not find a correlation; however, it is notable that half the patients did not have a known HPV status. We also found that a high neutrophil-to-lymphocyte ratio may predict worse outcomes, but additional correlative studies are ongoing at this time. In terms of toxicity, we didn’t see any new safety signals and no treatment-related grade 5 events, which was reassuring.

To conclude, in patients with advanced penile cancer refractory to platinum-based chemotherapy, avelumab was generally well tolerated and achieved an objective response rate of 17% with a median duration of response of 15 months, suggesting a small subset of patients may benefit from this treatment approach. However, biomarkers are urgently needed to better understand who these patients are and to refine patient selection accordingly. Progression-free survival and overall survival were really short, suggesting that this data is not transformative. Future studies will need to consider whether these agents should be evaluated in earlier disease settings or in combination with novel therapeutic strategies. Ultimately, large-scale collaborations, innovative study designs, and increased funding will be essential to accelerate drug development to improve outcomes for patients with rare tumors, including penile cancers.

We’d like to thank the patients and their families who participated in this study, the research personnel at each of the 3 cancer centers, Pfizer, who supported and provided study drug, as well as doctors Jang, Ali, Muhammad, and Powles for their support in this presentation. 

Source:

S Sridhar, Stecca CE, Fernandes R, et al. A phase II study of avelumab in locally advanced or metastatic penile cancer patients unfit for platinum-based chemotherapy or progressed on or after platinum-based chemotherapy (ALPACA). Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA37