<b>EGFR mutational status in penile cancer</b>

Lorenzo, Giuseppe Di; Buonerba, Carlo; Gaudioso, Gabriella; Gigantino, Vincenzo; Quarto, Giuseppe; Domenico, Renato De; Caraglia, Michele; Trolio, Rossella Di; Ascierto, Paolo A.; Placido, Sabino De; Perdonà, Sisto; Franco, Renato

doi:10.1517/14728222.2013.783571

Cited by 18 publications

(11 citation statements)

References 20 publications

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“…EGFR overexpression appeared to be universal and correlated with the grade of penile SCCs, and the expression of phosphorylated EGFR was recently found to be strongly related to an increase in the risk of recurrence and shorter overall survival in patients with N0-1 disease [5][6][7].…”

Section: Discussionmentioning

confidence: 98%

A case of penile squamous cell carcinoma treated with a combination of antiepidermal growth factor receptor antibody and chemotherapy

Men

Gou²,

Qiu³

et al. 2014

Anti-Cancer Drugs

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Our previous study showed that the features of epidermal growth factor receptor (EGFR)-RAS signaling in penile squamous cell carcinoma (SCC) suggested potential benefits of anti-EGFR monoclonal antibodies (mAbs) for penile SCC. Here, we report, for the first time, a combination of nimotuzumab (an EGFR mAb) with chemotherapy that resulted in a partial response in a 44-year-old patient with penile SCC, who developed bilateral inguinal node metastasis after primary partial penile amputation. The literature of case reports of anti-EGFR mAbs in penile SCC was also reviewed.

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Section: Discussionmentioning

confidence: 98%

A case of penile squamous cell carcinoma treated with a combination of antiepidermal growth factor receptor antibody and chemotherapy

Men

Gou²,

Qiu³

et al. 2014

Anti-Cancer Drugs

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“…In a literature review of individual data of 28 patients with advanced penile cancer receiving anti-EGFR monoclonal antibodies (cetuximab, panitumumab, and nimotuzumab), a 50% radiological response rate was achieved, but a median PFS of only approximately 3 months (interquartile range, 1.5–5.78, Di Lorenzo et al, 2015). From a biological perspective, EGFR appears a promising target in penile cancer, as it is universally expressed and frequently phosphorylated (Di Lorenzo et al, 2013a), but infrequently amplified (Di Lorenzo et al, 2013a), or mutated (Di Lorenzo et al, 2013b), while mutations of downstream signaling proteins (such as KRAS/BRAF) are rare (Gou et al, 2013). Nevertheless, we failed to identify a signal of prolonged OS associated with the use of cetuximab in our study cohort.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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.

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“…Two studies found that the presence of LNMs is higher for patients with human papillomavirus DNA-negative; however, the P values are not significant 1819. P53, Ki-67, E-cadherin, and epidermal growth factor receptor (EGFR) are suggested molecular prognostic markers in PSCC by some studies 16202122. Di Lorenzo et al 21.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of the degree of extranodal extension in patients with penile carcinoma

Wang

Zhu²,

Tang³

et al. 2014

Asian J Androl

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This study sought to assess the prognostic significance of the degree of extranodal extension (ENE) and several other risk factors in pathological ENE penile carcinoma. We analyzed prospectively collected data on a consecutive series of 31 chemotherapy-naive patients with proven ENE who underwent therapeutic regional lymphadenectomy. Postoperative external radiotherapy was then performed. We studied the extent of ENE utilizing a novel grading system and correlated patient grades with their outcome measures. ENE was graded as 1 - if the capsule of the lymph node (LN) was ruptured less than one-third of its circumference or 2 - if the capsule was disrupted more than one-third of its circumference or the entire LN was disrupted. We estimated overall survival (OS) using the Kaplan-Meier method. Multivariate analysis was performed according to the Cox proportional hazards model using factors that were identified as statistically significant in univariate analysis. The incidence rate of ENE was 51.8% in patients with pathological node-positive carcinoma of the penis. The median OS and 5-year survival were 18 months (95% confidence interval (CI), 14.4–21.6) and 23%, respectively. Prognostic variables on univariate analysis were ENE grade 2, ≥3 LNs with ENE, maximal LN ≥ 35 mm, ≥5 positive LNs and pelvic LN involvement. On multivariate analysis, only ENE grade 2 remained associated with decreased OS (hazard ratio (HR): 6.50). In conclusion, patients with ENE have a poor outcome, and ENE grade 2 is an independent predictive factor of poor OS in patients with pathological ENE penile carcinoma.

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EGFR mutational status in penile cancer

Abstract: The most frequent activating EGFR mutations detected in non-small setting lung cancer are absent in penile cancer (PC). Sequencing of the entire EGFR gene in patients with PC may provide useful insights, as its mechanism of overexpression and activation in PC remains unknown.

Cited by 18 publications

References 20 publications

A case of penile squamous cell carcinoma treated with a combination of antiepidermal growth factor receptor antibody and chemotherapy

A case of penile squamous cell carcinoma treated with a combination of antiepidermal growth factor receptor antibody and chemotherapy

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

Prognostic significance of the degree of extranodal extension in patients with penile carcinoma

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