Avelumab demonstrates activity in refractory penile cancer

Treatment of advanced penile cancer in patients who are refractory to or unfit for platinum-based chemotherapy using avelumab (Bavencio) may benefit some patients with the disease, but further study is needed, according to a presentation at the 2025 European Society for Medical Oncology Congress in Berlin, Germany.¹

At the beginning of her presentation, Srikala S. Sridhar, MD, MSc, FRCPC, a clinician investigator at Princess Margaret Cancer Center Cancer Clinical Research Unit in Toronto, Canada, noted that prior research has established that up 50% of penile cancer cases are human papillomavirus (HPV) related, and that approximately 30% to 60% of cancers express PD-L1.^2,3 She also noted that currently, no second-line treatment options exist, “highlighting a significant unmet need.”

Since immune checkpoint inhibitors have demonstrated activity and tolerability in other HPV-related cancers,⁴ Sridhar and her colleagues conducted the phase 2 ALPACA trial (NCT03391479) to evaluate the PD-L1 inhibitor avelumab in patients with penile cancer refractory to or unfit for platinum-based chemotherapy.

The multicenter, single-arm study included patients with locally advanced inoperable or metastatic penile cancer that is refractory or unfit for platinum, who have an ECOG performance status of 0-2, and who had no prior immune checkpoint inhibitor treatment. A total of 24 patients (of whom 23 were evaluable) received avelumab 10 mg/kg intravenously every 2 weeks until toxicity or progression. The primary end point was objective response rate (ORR) by investigator (iRECIST criteria), and secondary end points included progression-free survival (PFS), overall survival (OS), safety and tolerability, and correlative studies.

In terms of baseline characteristics, the median age was 58 years (range, 41-72). Seven (30%) patients had an ECOG performance status of 2, 19 (83%) had visceral metastases (lung, liver, bone, soft tissue), and 22 (96%) had received 1 prior line of platinum-based chemotherapy.

Regarding the primary end point, “4 patients showed a partial response, leading to a response rate of 17%. Disease control rate was 21%, and the median duration of response among the responders was 15.9 months,” Sridhar said.

At a median follow-up of 15 months (range, 4.3-7.1 months), median PFS was 1.7 months (95% CI: 1.5-1.8), and median OS was 3.9 months (95% CI: 2.6-9.9). The median number of treatment cycles completed was 3 (range, 1-72 cycles). Treatment was ongoing in 3 (13%) patients. Of the patients no longer on treatment, for 19 (83%) patients the reason was disease progression or death, and for 1 (4%) patient the reason was an adverse event (AE).

“In terms of correlative studies, we saw no clear correlation between HPV status and outcomes; however, many patients did not have their HPV status known. We also found a high neutrophil-to-lymphocyte ratio may predict worse outcomes, but additional correlative studies are ongoing at this time,” Sridhar said.

The investigators did not observe any new safety signals, and no patient experienced a treatment-related grade 5 AE.

“In conclusion, in patients with advanced penile cancer refractory to platinum-based chemotherapy, avelumab was well tolerated and achieved an objective response rate of 17%, with a median duration of response of about 15 months, suggesting a small subset of patients may benefit. But biomarkers are urgently needed to understand who these patients are and to refine patient selection,” Sridhar said.

“However,” she added, “PFS and OS were very short, suggesting this data is not transformative. Future studies will need to consider if these agents should be evaluated in earlier disease settings, or in combination with novel therapeutic strategies.”

DISCLOSURES: Sridhar noted consulting disclosures with AstraZeneca, Bayer, Bicycle Therapeutics, BMS, Daichi Sankyo, EMD Serono, Gilead, Janssen, Merck, and Pfizer, as well as institutional research funding from Pfizer, Bayer, and EMD Serono.

REFERENCES

1. Sridhar SS, 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: European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. LBA37. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2025_abstracts/LBA37.html.pdf

2. Christodoulidou M, Sahdev V, Houssein S, Muneer A. Epidemiology of penile cancer. Curr Probl Cancer. 2015;39(3):126-36. doi:10.1016/j.currproblcancer.2015.03.010

3. Udager AM, Liu T-Y, Skala SL, et al. Frequent PD-L1 expression in primary and metastatic penile squamous cell carcinoma: potential opportunities for immunotherapeutic approaches. Ann Oncol. 2016;27(9):1706-1712. doi:10.1093/annonc/mdw216

4. Taghizadeh H, Fajkovic H. Immunotherapy in the management of penile cancer-A systematic review. Cancers (Basel). 2025;17(5):883. doi:10.3390/cancers17050883