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Case Reports
. 2015 Dec 14:4:34.
doi: 10.1186/s40164-015-0029-7. eCollection 2015.

Near complete response after single dose of nivolumab in patient with advanced heavily pre-treated KRAS mutant pulmonary adenocarcinoma

Diwakar Davar  1 , Mark A Socinski  2 , Sanja Dacic  3 , Timothy F Burns  4
Affiliations
Case Reports

"V体育官网入口" Near complete response after single dose of nivolumab in patient with advanced heavily pre-treated KRAS mutant pulmonary adenocarcinoma

Diwakar Davar (V体育平台登录) et al. Exp Hematol Oncol. .

Abstract

The programmed death 1 (PD-1) receptor is expressed by activated T-cells and engaged by ligands PD-L1 and PD-L2 normally expressed by infiltrating immune cells in response to viral infection. The PD-1/PD-L1 axis is a negative inhibitory pathway that down-regulates T-cells but is also used by tumors to evade anti-tumor immunity. Antibodies targeting PD-1/PD-L1 axis are capable of restoring functional anti-tumor immunity and have demonstrated efficacy in a broad range of tumor types including non-small cell lung cancer in both squamous and adenocarcinoma histologies. Ongoing issues affecting clinical development of these agents include assessment of response, optimal duration of therapy in excellent responders, predictive biomarkers and mechanisms of resistance. In this report, we describe a patient with advanced KRAS mutant heavily pretreated pulmonary adenocarcinoma who developed an excellent response after a single-dose of nivolumab. Pre-treatment tumor was found to have moderate CD3 and PD-L1 positivity by immunohistochemical staining VSports手机版. Evaluation of exceptional responders and non-responders are critical to furthering our understanding of the mechanisms of action (and resistance) to these agents. .

Keywords: Adenocarcinoma; KRAS mutant; Lung cancer; Nivolumab; Programmed death receptor-1 (PD-1). V体育安卓版.

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V体育安卓版 - Figures

Fig. 1
Fig. 1
Changes in Bi-dimensional tumor measurements of target and non-target lesions. Computer tomography (CT) scans depict imaging studies done on 5/13/2015 (above) and 7/15/2015 (middle). Lower graph depicts changes in size of target and non-target lesions at both time-points. Tumors were evaluated using Response Evaluation Criteria In Solid Tumors (RECIST v1.1). Left axis depicts maximal bi-dimensional measurement for 4 (1 target and 3 non-target) lesions while right axis depicts sum of maximal bi-dimensional measurements for all 4 lesions. All measurements are in mm. Nivolumab 3 mg/kg was administered on 5/20/2015 but subsequent doses were missed given multiple admissions. Prior to resumption of therapy following multiple admissions, a restaging scan was repeated on 7/15/2015. Remarkably, all lesions had shrunk considerably with 2 non-target lesions (left pleural nodule and para esophageal lymph node) disappearing completely after a single dose of nivolumab. Patient received 3 doses of nivolumab between 7/8/2015 and 8/12/2015. Therapy is ongoing with continued response
Fig. 2
Fig. 2
Histopathological analysis of pre-treatment tumor tissue. Pre-treatment formalin-fixed paraffin-embedded tissue specimen was stained for CD3, CD8 and PD-L1 by immunohistochemistry. Sections indicate presence of CD3+ and CD8+ T-cells though CD3+ T-cells outnumbered CD8+ T-cells. PD-L1 staining was heterogenous, localized to tumor tissue and of moderate intensity (2+, using method previously described by Taube JM et al., Sci Transl Med 2012)
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"VSports" References

    1. Riely GJ, Marks J, Pao W. KRAS mutations in non-small cell lung cancer. Proc Am Thorac Soc. 2009;6(2):201–205. doi: 10.1513/pats.200809-107LC. - VSports手机版 - DOI - PubMed
    1. Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med. 2011; 3(75):75ra26. - PMC - PubMed
    1. Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med 2012; 4(120):120ra17. - PMC - PubMed
    1. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA. 2002;99(19):12293–12297. doi: 10.1073/pnas.192461099. - DOI - PMC - PubMed
    1. Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol. 2007;19(7):813–824. doi: 10.1093/intimm/dxm057. - DOI - PubMed

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