Dr Sridhar on the Importance of Patient Selection for Benefit With Avelumab in PSCC

"[It is vital to] think about where in the treatment [course] and [in which] patient population [avelumab is best utilized]. Do we want to focus on those with node-only disease, or those with disease localized to the penile area? That might be the other thing to think about."

Srikala Sridhar, MD, MSc, FRCPC, a clinician investigator at Princess Margaret Cancer Center Cancer Clinical Research Unit, discussed how modest efficacy outcomes from the phase 2 ALPACA study (NCT03391479) reinforce the importance of patient selection when considering immune checkpoint inhibition in penile squamous cell carcinoma (PSCC).

As presented during the 2025 ESMO Congress, findings from ALPACA showed a confirmed objective response rate (ORR) of 17% for avelumab (Bavencio) in this patient population (n = 23), with 4 patients (17%) achieving a partial response. One patient (4%) achieved stable disease, yielding a disease control rate for 24 weeks or more of 21%. Although responses were infrequent, they proved durable among responders, with the median duration of response reaching 15.9 months. Despite the durability observed in responders, Sridhar noted that the overall survival metrics indicated that the data were "non transformative".

The median progression-free survival (PFS) was short at 1.7 months (95% CI 1.5-1.8), and the median overall survival (OS) was also limited at 3.9 months (95% CI 2.6-9.9).

Sridhar attributed these relatively short outcomes partially to the patient characteristics, noting that participants generally had an ECOG performance status of 1 or 2 and were heavily pretreated. Correlative analyses from the trial offered additional insight, revealing that although there was no clear association between human papillomavirus status and outcomes, a high neutrophil-to-lymphocyte ratio appeared to predict worse outcomes.

Sridhar emphasized the importance of optimizing outcomes by rethinking where these treatments are placed and who receives them. She suggested that moving treatments like immune checkpoint inhibitors earlier in the disease course—such as the first-line or neoadjuvant settings—might yield greater benefits. Furthermore, Sridhar stated that she was unsure if single-agent immune checkpoint inhibition was optimal, proposing that combining avelumab with another agent may be more important than continuing single-agent studies. Optimizing patient selection requires careful consideration of the disease setting, potentially focusing on patients with localized disease or those with node-only disease, she concluded.

Disclosures: Sridhar reports financial and personal interests and a role on the advisory board for Astellas, AstraZeneca, Bayer, BMS, EMD Serono, Pfizer, Seagen, Gilead, Bicycle Therapeutics; financial Interests, and receipt of institutional and unrestricted research grants to institution for developing a database from Seagen; financial Interests with receipt of institutional research grants from Pfizer.

Reference

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: 2025 European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. LBA37