ICIs Demonstrate Clinical Activity in Metastatic Penile Cancer

"The findings of this international Global Society of Rare Genitourinary Tumors (GSRGT) cohort study of patients with advanced [penile squamous cell carcinoma] suggest that ICI-based therapy is safe and associated with clinical benefit in a small subset of patients," according to the study authors.

Immune checkpoint inhibitors (ICIs) demonstrated clinical benefit in a subset of patients with locally advanced or metastatic penile squamous cell carcinoma, according to findings from an international cohort study published in Journal of the National Cancer Institute.

Among 92 evaluable patients in the overall population who received treatment with ICIs, the median overall survival (OS) was 9.8 months (95% CI, 7.7-12.9), and the 12-month OS rate was 33%. Additionally, the median progression-free survival (PFS) was 3.2 months (95% CI, 2.5-4.2), and the PFS rate at 6 months was 25%. Among 74 patients who received ICIs in the second line and beyond, the median OS was 8.3 months (95% CI, 7.5-12.8), and the median PFS was 3.3 months (95% CI, 2.2-4.7). The corresponding values for patients who received ICI monotherapy (n = 65) were 9.5 months (95% CI, 7.7-13.0) months and 2.8 months (95% CI, 2.1-3.4).

Of 85 patients who were evaluable for response in the overall population, the overall response rate (ORR) was 13%, which included complete responses (CRs) in 2 patients and partial responses (PRs) in 9 patients. The median duration of response (DOR) was 8.1 months (interquartile range [IQR], 4.7-23.6). Among 68 patients who began treatment in the second line or later, the ORR was 13%. Among those who received ICI monotherapy, the ORR was 8.5% (95% CI, 2.8%-18.7%), and the median DOR was 8.1 months (IQR, 4.7-19.0).

In patients with lymph node–only disease and those with visceral/bone metastatic disease, respectively, the median OS was 11.4 months (95% CI, 7.9-not reached [NR]) compared with 7.7 months (95% CI, 6.4-12.5; P = .023). Additionally, the median PFS in each group was 2.8 months (95% CI, 1.9-NR) vs 3.3 months (95% CI, 2.3-4.2; P = .056), and the ORR was 35% vs 7% (odds ratio, 6.77; 95% CI, 1.47-36.6; P = .056). Investigators reported no significant differences in OS, PFS, or ORR between patients with bone metastases (n = 21) vs those without (n = 55).

“The findings of this international Global Society of Rare Genitourinary Tumors (GSRGT) cohort study of patients with advanced [penile squamous cell carcinoma] suggest that ICI-based therapy is safe and associated with clinical benefit in a small subset of patients,” the study authors wrote. “Given that [penile squamous cell carcinoma] is an orphan disease with suboptimal systemic therapy options and formidable challenges in trial accrual, a paradigm of high-quality, real-world studies to investigate the activity of new agents may be considered to make therapeutic advances.”

Investigators of this retrospective study analyzed data from patients who received ICI-based treatment for advanced or metastatic penile squamous cell carcinoma across 24 institutions in the GSRGT consortium from the United States, Europe, and Asia. Estimating OS and PFS involved use of the Kaplan-Meier method, and investigators determined ORR per RECIST v1.1 criteria. Treatment-related adverse effects (TRAEs) were assessed based on CTCAE v5.0 guidelines.

Patients with biopsy-proven advanced penile squamous cell carcinoma who received any anti–PD-L1 agent alone or in combination with anti–ÇTLA-4 agents, chemotherapy, or tyrosine kinase inhibitors between 2015 and 2022 were eligible for inclusion in the study.

The median patient age was 62 years (IQR, 53-70), and 37% of patients were current or former smokers. Additionally, most patients were White (74%), non-Hispanic (71%), and had metastatic disease (90%). The most common regimens included pembrolizumab (Keytruda) monotherapy (28%) followed by nivolumab (Opdivo) monotherapy (17%) and cemiplimab (Libtayo) monotherapy (16%).

An ECOG performance status of at least 1 (HR, 2.86; 95% CI, 1.54-5.31; P = .0009), neutrophil/lymphocyte ratio (NLR; HR, 1.04; 95% CI, 1.01-1.06; P = .011), and presence of visceral metastases (HR, 2.09; 95% CI, 1.16-3.75; P = .014) correlated with worse OS based on multivariate analyses. Additionally, higher age correlated with better OS (HR, 0.97; 95% CI, 0.95-0.99; P = .013). Investigators also observed an association between age (HR, 0.97; 95% CI, 0.95-0.99; P = .01), NLR (HR, 1.04; 95% CI, 1.00-1.08; P = .03), an ECOG performance status of at least 1 (HR, 2.76; 95% CI, 1.59-4.79; P = .0003), and visceral metastases (HR, 1.63; 95% CI, 0.96-2.76; P = .07) and PFS, according to a multivariable analysis.

Overall, any-grade TRAEs occurred in 29% of patients, and 10% experienced grade 3/4 TRAEs. The most common TRAEs included hepatitis (10%), diarrhea/colitis (8.7%), and skin and thyroid events (7.6%).

Reference

Zarif TE, Nassar AH, Pond GR, et al. Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors. J Natl Cancer Inst. Published online, August 11, 2023. doi:10.1093/jnci/djad155