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, Naoya Yamazaki

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Background: An anti-programmed cell death protein 1 monoclonal antibody, nivolumab, is one of the most effective drugs for advanced melanoma. Tumor cellderived 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.

Original languageEnglish
Pages (from-to)77404-77415
Number of pages12
JournalOncotarget
Volume7
Issue number47
DOIs
Publication statusPublished - 2016

Fingerprint

Melanoma
L-Lactate Dehydrogenase
Survival
Programmed Cell Death 1 Receptor
Neutrophils
Therapeutics
Cancer Care Facilities
Tokyo
Lymphocyte Count
Tumor Burden
C-Reactive Protein
Neoplasms
Japan
Multivariate Analysis
Biomarkers
Monoclonal Antibodies
nivolumab
Skin
Serum
Pharmaceutical Preparations

Keywords

  • Absolute lymphocyte count
  • Absolute neutrophil count
  • Early markers for outcome
  • Metastatic melanoma
  • Nivolumab

ASJC Scopus subject areas

  • Oncology

Cite this

Nakamura, Y., Kitano, S., Takahashi, A., Tsutsumida, A., Namikawa, K., Tanese, K., ... Yamazaki, N. (2016). Nivolumab for advanced melanoma: Pretreatment prognostic factors and early outcome markers during therapy. Oncotarget, 7(47), 77404-77415. https://doi.org/10.18632/oncotarget.12677

Nivolumab for advanced melanoma : Pretreatment prognostic factors and early outcome markers during therapy. / Nakamura, Yoshio; Kitano, Shigehisa; Takahashi, Akira; Tsutsumida, Arata; Namikawa, Kenjiro; Tanese, Keiji; Abe, Takayuki; Funakoshi, Takeru; Yamamoto, Noboru; Amagai, Masayuki; Yamazaki, Naoya.

In: Oncotarget, Vol. 7, No. 47, 2016, p. 77404-77415.

Research output: Contribution to journalArticle

Nakamura, Y, Kitano, S, Takahashi, A, Tsutsumida, A, Namikawa, K, Tanese, K, Abe, T, Funakoshi, T, Yamamoto, N, Amagai, M & Yamazaki, N 2016, 'Nivolumab for advanced melanoma: Pretreatment prognostic factors and early outcome markers during therapy', Oncotarget, vol. 7, no. 47, pp. 77404-77415. https://doi.org/10.18632/oncotarget.12677
Nakamura, Yoshio ; Kitano, Shigehisa ; Takahashi, Akira ; Tsutsumida, Arata ; Namikawa, Kenjiro ; Tanese, Keiji ; Abe, Takayuki ; Funakoshi, Takeru ; Yamamoto, Noboru ; Amagai, Masayuki ; Yamazaki, Naoya. / Nivolumab for advanced melanoma : Pretreatment prognostic factors and early outcome markers during therapy. In: Oncotarget. 2016 ; Vol. 7, No. 47. pp. 77404-77415.
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T2 - Pretreatment prognostic factors and early outcome markers during therapy

AU - Nakamura, Yoshio

AU - Kitano, Shigehisa

AU - Takahashi, Akira

AU - Tsutsumida, Arata

AU - Namikawa, Kenjiro

AU - Tanese, Keiji

AU - Abe, Takayuki

AU - Funakoshi, Takeru

AU - Yamamoto, Noboru

AU - Amagai, Masayuki

AU - Yamazaki, Naoya

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N2 - Background: An anti-programmed cell death protein 1 monoclonal antibody, nivolumab, is one of the most effective drugs for advanced melanoma. Tumor cellderived 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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