Evidence for Efficacy of Treatment With the Anti-PD-1 Mab Nivolumab in Radiation and Multichemorefractory Advanced Penile Squamous Cell Carcinoma

Trafalis, Dimitrios T.; Alifieris, Constantinos; Kalantzis, Anastasios; Verigos, Kosmas; Vergadis, Chrysovalantis; Sauvage, Sébastien

doi:10.1097/cji.0000000000000221

Cited by 37 publications

(21 citation statements)

References 12 publications

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“…Furthermore, high-risk human papilloma virus-negative status (hrHPV) and diffuse PD-L1 expression in the tumor field demonstrated significant correlation with poor disease-specific survival with an HR of 9.73 ( p -value < 0.01), and HR of 2.81 ( p -value=0.03), respectively [ 23 ]. Moreover, in a recent case study, Trafalis et al reported a partial response to nivolumab, an anti-PD-1 monoclonal antibody, in a patient with advanced hrHPV negative penile SCC refractory to chemoradiation therapies [ 34 ]. The authors reported a >80% reduction in tumor volume after eight cycles of nivolumab.…”

Section: Pd-l1 Expressionmentioning

confidence: 99%

The Immune Microenvironment in Penile Cancer and Rationale for Immunotherapy

Ahmed

Falasiri

Hajiran

et al. 2020

JCM

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Penile cancer is an extremely rare malignancy that accounts for approximately 1% of cancer deaths in the United States every year. While primary penile cancer can be managed surgically, advanced and metastatic forms of the disease require more aggressive management plans with systemic chemotherapy and/or radiotherapy. Despite the meaningful response to systemic treatments, the 2-year progression-free survival and disease-specific survival have shown disappointing results. Therefore, there is a crucial need for alternative treatment options with more favorable outcomes and a lower toxicity profile. There are currently extensive studies of tumor molecular biology and clinical trials with targeted molecular therapies, such as PD-1, PD-L1, and CTLA-4. In this review, we will describe the penile cancer microenvironment, and summarize the rationale for immunotherapy in penile cancer patients.

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Section: Pd-l1 Expressionmentioning

confidence: 99%

The Immune Microenvironment in Penile Cancer and Rationale for Immunotherapy

Ahmed

Falasiri

Hajiran

et al. 2020

JCM

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“…3,9-11 It has been used with some success in metastatic penile cancers, although evidence so far has been restricted to clinical cases. 12,13 However, the rational for its use is sound, as studies have found expression of PD-L1 in 40% of penile SCC. 14 Several phase 2 trials are underway to evaluate the role of immunotherapy in advanced penile cancer.…”

Section: Discussionmentioning

confidence: 99%

Penile Lymphoepithelioma-Like Carcinoma: A Rare Case With PD-L1 Expression

et al. 2021

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Most malignant tumors of the penis are squamous cell carcinomas (SCC), being divided in 2 groups, one human papillomavirus (HPV)-related and another non-HPV-related, with lymphoepithelioma-like carcinoma (LELC) being one of the rarest HPV-related SCC. In this article, we report a case of a 50-year-old man who presented testicular swelling and pain for the past 3 months. A penile mass was identified, and the patient was submitted to a total penectomy. The penectomy specimen showed an ulcerated lesion at the glans reaching the cavernous bodies. Microscopic examination showed undifferentiated epithelial cells with syncytial growth pattern mix with a dense lymphoplasmacytic infiltrate, consistent with LELC. The tumor cells expressed p16 and all 3 different clones of PDL1 (22C3, SP263, and SP142). The patient is alive and well with a follow-up of 3 months. To our knowledge, this is the third LELC of the penis reported in literature and the first case reported with PDL1 expression.

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“…PD-L1 is detected in 40-60% of PSCC cases and is correlated with poor prognosis and the number of tumor-infiltrating lymphocytes 48 . In a case report, a patient with an HPV-negative PSCC treated with nivolumab experienced a partial response 67 . Currently, there are multiple ICB trials recruiting patients with PSCC (e.g.…”

Section: Discussionmentioning

confidence: 99%

Effective combinatorial immunotherapy for penile squamous cell carcinoma

et al. 2020

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Penile squamous cell carcinoma (PSCC) accounts for over 95% of penile malignancies and causes significant mortality and morbidity in developing countries. Molecular mechanisms and therapies of PSCC are understudied, owing to scarcity of laboratory models. Herein, we describe a genetically engineered mouse model of PSCC, by co-deletion of Smad4 and Apc in the androgen-responsive epithelium of the penis. Mouse PSCC fosters an immunosuppressive microenvironment with myeloid-derived suppressor cells (MDSCs) as a dominant population. Preclinical trials in the model demonstrate synergistic efficacy of immune checkpoint blockade with the MDSC-diminishing drugs cabozantinib or celecoxib. A critical clinical problem of PSCC is chemoresistance to cisplatin, which is induced by Pten deficiency on the backdrop of Smad4/Apc co-deletion. Drug screen studies informed by targeted proteomics identify a few potential therapeutic strategies for PSCC. Our studies have established what we believe to be essential resources for studying PSCC biology and developing therapeutic strategies.

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Evidence for Efficacy of Treatment With the Anti-PD-1 Mab Nivolumab in Radiation and Multichemorefractory Advanced Penile Squamous Cell Carcinoma

Cited by 37 publications

References 12 publications

The Immune Microenvironment in Penile Cancer and Rationale for Immunotherapy

The Immune Microenvironment in Penile Cancer and Rationale for Immunotherapy

Penile Lymphoepithelioma-Like Carcinoma: A Rare Case With PD-L1 Expression

Effective combinatorial immunotherapy for penile squamous cell carcinoma

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