Early depth of tumor shrinkage and treatment outcomes in non-small cell lung cancer treated using Nivolumab

  • Hayato Kawachi
  • Daichi FujimotoEmail author
  • Takeshi Morimoto
  • Kazutaka Hosoya
  • Yuki Sato
  • Mariko Kogo
  • Kazuma Nagata
  • Atsushi Nakagawa
  • Ryo Tachikawa
  • Keisuke Tomii


Background It would be useful to have criteria for predicting long-term treatment responses to immune checkpoint inhibitors (ICIs). Maximum depth of response correlates with treatment outcomes among patients receiving programmed death protein 1 axis inhibitors for non-small cell lung cancer (NSCLC). We investigated associations between early depth of response and survival outcomes among patients receiving nivolumab for NSCLC. Methods Using records from prospective observational cohorts, we identified 83 previously treated advanced patients with NSCLC who received nivolumab during 2016–2017. Thirty-one patients who achieved disease control were analyzed. Tumor assessments followed the Response Evaluation Criteria in Solid Tumors (RECIST). Using Kaplan-Meier and receiver operating characteristic (ROC) curve analyses, treatment outcomes were compared with percent tumor reductions from baseline to the first evaluation (8–12 weeks after starting nivolumab). Results Early depth of response was predictive of 6-month progression-free survival (area under the ROC curve, 0.848). Based on ROC results, early tumor shrinkage was defined as a > 10% reduction by the first evaluation. Early tumor shrinkage was associated with significantly longer median progression-free survival (early tumor shrinkage: 16.6 months, 95% confidence interval [CI] 8.5 months–not reached; no early shrinkage: 5.1 months, 95% CI 3.9–6.8 months; P < 0.001) and significantly longer median overall survival (P = 0.046). Conclusions Early depth of tumor shrinkage was associated with outcomes after ICI treatment. Because of its simplicity and predictive ability, early tumor shrinkage may be a promising factor for use in clinical settings. However, confirmation of our results is needed.


Immune checkpoint inhibitor Non-small cell lung cancer Depth of response Treatment outcome Retrospective study 



Non-small cell lung cancer


Immune checkpoint inhibitor


Programmed death protein 1


Programmed death ligand 1


overall survival


Response Evaluation Criteria in Solid Tumors


Progression-free survival


Epidermal growth factor receptor gene


Tyrosine kinase inhibitor


Computed tomography


Receiver operating characteristic


Confidence interval


Progression-free survival



The authors thank Keiko Sakuragawa for her administrative assistance.


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Disclosure of potential conflicts of interest

Dr. Kawachi has received lecture fees from Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical, Merck Sharp and Dohme, and Taiho Pharmaceutical. Dr. Fujimoto has received lecture fees from Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., Chugai Pharmaceutical, AstraZeneca, Merck Sharp and Dohme, and Taiho Pharmaceutical. Dr. Hosoya has received lecture fees from Chugai Pharmaceutical, Merck Sharp and Dohme, and Taiho Pharmaceutical. Dr. Sato has received lecture fees from Ono Pharmaceutical Co., Ltd. Dr. Tomii has received lecture fees from Chugai Pharmaceutical, AstraZeneca, and Taiho Pharmaceutical. The remaining authors have declared that they have no conflicts of interest.

Ethical approval

All study procedures complied with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.

Supplementary material

10637_2019_770_MOESM1_ESM.pdf (110 kb)
Online Resource 1 Supplementary Figure Kaplan-Meier curves for progression-free survival among patients with stable disease at the first evaluation (N = 19). The survival analysis is stratified by early tumor shrinkage (present vs. absent). Each curve is labelled with the median survival time, the total number events, and the total number of patients (PDF 109 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hayato Kawachi
    • 1
  • Daichi Fujimoto
    • 1
    Email author
  • Takeshi Morimoto
    • 2
    • 3
  • Kazutaka Hosoya
    • 1
  • Yuki Sato
    • 1
  • Mariko Kogo
    • 1
  • Kazuma Nagata
    • 1
  • Atsushi Nakagawa
    • 1
  • Ryo Tachikawa
    • 1
  • Keisuke Tomii
    • 1
  1. 1.Department of Respiratory MedicineKobe City Medical Center General HospitalKobeJapan
  2. 2.Clinical Research CenterKobe City Medical Center General HospitalKobeJapan
  3. 3.Department of Clinical EpidemiologyHyogo College of MedicineNishinomiyaJapan

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