Refractory Metastatic Squamous Cell Carcinoma Research Articles

セツキシマブ・パクリタキセル併用療法が有効であった難治性転移性有棘細胞癌の1例

46歳，男性。下口唇の慢性円板状エリテマトーデス（DLE）の瘢痕部に急激に増大する腫瘤が出現し，病理組織学的に有棘細胞癌と診断した。選択的シスプラチン動注と放射線治療を行い，腫瘤は著明に縮小したが，その後右頸部リンパ節転移を認め，頸部リンパ節郭清術を行った。しかしその後，両側頸部，正中下顎リンパ節転移が出現し，S－1＋シスプラチン投与，放射線治療を行うも両側腋窩リンパ節転移が出現した。腫瘍細胞が上皮成長因子受容体（epidermal growth factor receptor：EGFR）強陽性であり，セツキシマブおよびパクリタキセルの併用療法を行ったところ，転移性病変は著明に縮小した。

Abstract CT131: NCI#9673 phase II study of nivolumab in refractory metastatic squamous cell carcinoma of the anal canal: Immunologic correlates of response

Abstract Introduction: The incidence of squamous cell carcinoma of the anal canal (SCCA) continues to increase, with no standardized treatment options for patients with refractory metastatic disease. The development of SCCA is associated with human papillomavirus infection (HPV) and impaired immunity. Nivolumab is a monoclonal antibody targeting the programmed-death 1 (PD-1) ligand on T cells and may restore T-cell activity against tumor cells. The efficacy for nivolumab for metastatic SCCA has not been evaluated. Methods: Patients with at least one prior treatment for metastatic SCCA were treated with nivolumab (3 mg/kg) intravenously every 2 weeks in this single-arm, Simon two-stage phase 2 trial. PD-L1 expression was not an inclusion criterion. A total of 39 patients were enrolled through the ETCTN network. At our institution, an exploratory correlative analysis of paired tumor biopsies (pre-treatment and on-treatment) and of serial peripheral blood samples was conducted. All tissues samples were analyzed by immunohistochemistry (IHC) and flow cytometry by the MDACC immunotherapy platform to identify various immune cell subsets. Results from radiographic responders and non-responders were compared by Mann-Whitney test to identify biomarkers associated with treatment response. Results: In this subset analysis, 17 patients consented to tissue collection. Four patients had inadequate sample for analysis. Immune monitoring studies of pre-treatment tumor samples by IHC (n = 13) revealed a significantly higher percentage of CD3 T cells (p = 0.02), CD8 T cells (p = 0.01), granzyme-B (p = 0.005), PD-1 (p = 0.02), and PD-L1 on tumor epithelial cells (p = 0.005) in samples from patients who were scored as responders (n = 4) as compared to non-responders (n = 9). Five additional markers (CD20, CD45R0, CD68, FoxP3, OX40) measured by IHC did not show statistically significant differences. In addition, flow cytometry studies on available tumor samples (n = 12) indicated that patients who scored as responders had a significantly higher frequency of TIM-3+ CD8 T cells (p = 0.003) and PD-L1+ CD45+ immune cells (p = 0.03) in pre-treatment samples. Of note, responder patients had a trend towards a decrease in frequency of TIM-3+ CD8 T cells in post-treatment tumor samples. Conclusions: In the first prospective phase II trial ever for refractory metastatic SCCA, our exploratory analysis of pre- and on-treatment tissue specimens revealed potential correlations between immunologic biomarkers and clinical outcomes to nivolumab. Additional immune monitoring data will be provided. Citation Format: Van Morris, Armeen Mahvash, Luis Vence, Jorge Blando, Robert A. Wolff, Aki Ohinata, Chimela Ohaji, James Allison, Padmanee Sharma, Cathy Eng. NCI#9673 phase II study of nivolumab in refractory metastatic squamous cell carcinoma of the anal canal: Immunologic correlates of response. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT131.

NCI9673: A multi-institutional eETCTN phase II study of nivolumab in refractory metastatic squamous cell carcinoma of the anal canal (SCCA).

3503Background: The incidence of SCCA continues to rise annually in the US. 20% of patients (pts) will develop metastatic (met) disease which lacks a consensus approach to treatment. SCCA is largel...

Reovirus: A Targeted Therapeutic—Progress And Potential

Medical therapy of patients with malignancy requires a paradigm shift through development of new drugs with a good safety record and novel mechanisms of activity. While there is no dearth of such molecules, one particular agent, "reovirus" is promising by its ability to target cancer cells with aberrant signaling pathways. This double-stranded RNA virus has been therapeutically formulated and has rapidly progressed from preclinical validation of anticancer activity to a phase III registration study in platinum refractory metastatic squamous cell carcinoma of the head and neck. During this process, reovirus has shown safety both as a single agent when administered intratumorally and intravenously, as well as in combination therapy, with multiple chemotherapeutics such as gemcitabine, carboplatin/paclitaxel, and docetaxel; and similarly with radiation. The scientific rationale for its development as an anticancer agent stems from the fact that it preferentially replicates in and induces lyses of cells with an activated Kras pathway. As documented in many previous studies, the initial observation of greater tropism in Kras-compromised situation might certainly not be the sole and possibly not even the predominant reason for enhanced virulence. All the same, scientists have emphasized on Kras optimistically due to its high prevalence in various types of cancers. Incidence of Kras mutation has been found to be highest in pancreatic cancer (85%-90%) followed by colorectal (35-45%) and lung (25-30%). Reovirus, in fact has the potential not only as a therapy but also as a tool to unravel the aberrant cellular pathway leading to carcinogenicity.