Prognostic and Predictive Factors in Patients with Advanced Penile Cancer Receiving Salvage (2nd or Later Line) Systemic Treatment: A Retrospective, Multi-Center Study

Abstract

Introduction and objectives: Metastatic penile squamous cell carcinoma (PSCC) is associated with dismal outcomes with median overall survival (OS) of 6–12 months in the first-line and <6 months in the salvage setting. Given the rarity of this disease, randomized trials are difficult. Prognostic risk models may assist in rational drug development by comparing observed outcomes in nonrandomized phase II studies and retrospective data vs. predicted outcomes based on baseline prognostic factors in the context of historically used agents. In this retrospective study, we constructed a prognostic model in the salvage setting of PSCC patients receiving second or later line systemic treatment, and also explored differences in outcomes based on type of treatment.Materials and methods: We performed a chart review to identify patients with locally advanced unresectable or metastatic PSCC who received second or later line systemic treatment in centers from North America and Europe. The primary outcome was OS from initiation of treatment, with secondary outcomes being progression-free survival (PFS) and response rate (RR). OS was estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to identify prognostic factors for outcomes using univariable and multivariable models.Results: Sixty-five patients were eligible. Seventeen of 63 evaluable patients had a response (27.0%, 95% confidence interval [CI] = 16.6–39.7%) and median OS and PFS were 20 (95% CI = 20–21) and 12 (95% CI = 12, 16) weeks, respectively. Visceral metastasis (VM) and hemoglobin (Hb) ≤ 10 gm/dl were consistently significant poor prognostic factors for both OS and PFS, and Hb was also prognostic for response. The 28 patients with neither risk factor had a median OS (95% CI) of 24 (20–40) weeks and 1-year (95% CI) OS of 13.7% (4.4–42.7%), while the 37 patients with 1 or 2 risk factors had median OS (95% CI) of 20 (16–20) weeks and 1-year (95% CI) OS of 6.7% (1.8–24.9%). Cetuximab-including regimens were associated with a trend for improved RR compared to other agents (Odds ratio = 5.05, 95% CI = 0.84–30.37, p = 0.077). Taxanes vs. non-taxane, and combination vs. single agent therapy was not associated with improved outcomes. The study is limited by its modest sample size.Conclusion: This is the first prognostic classification proposed for patients receiving salvage systemic therapy for advanced PSCC. The presence of VM and Hb ≤ 10 gm/dl was associated with poor OS and PFS. Cetuximab appeared to be associated with better RR. This prognostic model may assist in salvage therapy drug development for this orphan disease by improving interpretation of outcomes seen in nonrandomized data.

Penile cancer: a Brazilian consensus statement for low- and middle-income countries

“…Currently, the role of anti-epidermal growth factor receptor (anti-EGFR) targeted therapy (cetuximab, panitumumab, and dacomitinib) in the treatment of advanced penile cancer is investigational (recommendation, LE: 1b-) as the available literature is still limited (Necchi et al 2018 ; Carthon et al 2014 ; Brown et al 2014 ; Buonerba et al 2016 ). Anti-EGFR is an option in unresectable, relapsed, and/or metastatic cancer as a second-line treatment, associated or not associated with chemotherapy, after TIP/TPF failure (recommendation, LE: 4), showing a trend to a higher response rate compared with other chemotherapy regimens (Buonerba et al 2016 ). …”

A phase II trial of cabazitaxel as second line chemotherapy in relapsed locally advanced and/or metastatic carcinoma of the penis

“…Taxanes have been shown to be efficacious as part of a multidrug regimen in the front-line setting. 11,12 Despite this proven efficacy, a retrospective chart review by Buonerba et al., 19 which included 65 patients across North America, Europe, and Japan, reported that 74% of the patients received taxanes as second-line chemotherapy. This is consistent with the fact taxanes are not universally used in a first-line setting.…”

“…Buonerba et al. 19 retrospectively analysed 65 patients who received second-line systemic therapy. The presence of visceral metastases and haemoglobin ≤10 g/dL were associated with poor outcomes.…”

Advances in Understanding of Penile Carcinogenesis: The Search for Actionable Targets

“…A meta-analysis of 28 patients in total demonstrated 50% response rate with a median progression free survival (PFS) of 3 months (1.5–5.78) [ 51 ]. Another review of 65 patients, of which 17 patients were treated with cetuximab-including regimens, showed a trend for improved response (OR = 5.05, p = 0.077) when compared to those who received taxane-based regimens alone [ 52 ]. These results seem to indicate that although EGFR pathway plays an initial role in penile carcinogenesis, those with advanced disease continue to benefit from standard chemotherapy regimens in addition to anti- EGFR therapy.…”