Oncotarget

Research Papers:

Nivolumab for advanced melanoma: pretreatment prognostic factors and early outcome markers during therapy

Yoshio Nakamura, Shigehisa Kitano _, Akira Takahashi, Arata Tsutsumida, Kenjiro Namikawa, Keiji Tanese, Takayuki Abe, Takeru Funakoshi, Noboru Yamamoto, Masayuki Amagai and Naoya Yamazaki

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Oncotarget. 2016; 7:77404-77415. https://doi.org/10.18632/oncotarget.12677

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Abstract

Yoshio Nakamura1,3, Shigehisa Kitano2,*, Akira Takahashi1, Arata Tsutsumida1, Kenjiro Namikawa1, Keiji Tanese3, Takayuki Abe4, Takeru Funakoshi3, Noboru Yamamoto2, Masayuki Amagai3, Naoya Yamazaki1,*

1Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan

2Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan

3Department of Dermatology, Keio University School of Medicine, Tokyo, Japan

4Department of Preventive Medicine and Public Health, Biostatistics Unit at Clinical Translational Research Center, Keio University School of Medicine, Tokyo, Japan

*These authors have contributed equally to this work

Correspondence to:

Shigehisa Kitano, email: skitano@ncc.go.jp

Keywords: nivolumab, metastatic melanoma, absolute lymphocyte count, absolute neutrophil count, early markers for outcome

Received: June 07, 2016    Accepted: September 28, 2016    Published: October 15, 2016

ABSTRACT

Background: An anti-programmed cell death protein 1 monoclonal antibody, nivolumab, is one of the most effective drugs for advanced melanoma. Tumor cell-derived or immune cell-derived markers and clinical predictors such as serum lactate dehydrogenase (LDH) and cutaneous adverse events, have already been described as prognostic factors for advanced melanoma treated with nivolumab. We sought to identify further clinical predictors that can be determined in routine clinical practice.

Methods: We retrospectively analyzed clinical findings of 98 consecutive patients with unresectable stage III or IV melanoma treated with nivolumab, at the National Cancer Center Hospital or at Keio University Hospital, in Tokyo, Japan, between July 2014 and July 2016. These patients had been administered nivolumab at a dose of 2mg/kg every 3 weeks.

Results: As for pretreatment prognostic factors, ECOG performance status (PS) ≥1, maximum tumor diameters of ≥30mm, elevated LDH and elevated C-reactive protein were significantly associated with poor overall survival (OS) (hazard ratio [HR] 0.29 [P<0.001], HR 0.40 [p=0.003], HR 0.29 [P<0.001], HR 0.42 [P=0.004], respectively) on univariate analysis. Among these factors, PS and LDH were identified as independent variables by multivariate analysis. As for early markers examined during therapy, patients with absolute lymphocyte count (ALC) ≥ 1000/μl (Week3: HR 0.40 [P=0.004], Week6: HR 0.33 [P=0.001]) and absolute neutrophil count (ANC) <4000/μl (Week3: HR 0.46 [P=0.014], Week6: HR 0.51 [P=0.046]) had significantly better OS.

Conclusion: ALC≥1000/μl and ANC<4000/μl during treatment appear to be early markers associated with OS. Nivolumab might have minimal efficacy in patients with a massive tumor burden.


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