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Impact of Prior Ramucirumab Use on Treatment Outcomes of Checkpoint Inhibitors in Advanced Gastric Cancer Patients

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Abstract

Background

A taxane plus ramucirumab as second-line therapy followed by a checkpoint inhibitor (CPI) in third line has become a standard treatment strategy for advanced gastric cancer.

Objective

Herein, we investigated the impact of prior ramucirumab use on the efficacy of third-line immunotherapy and performed an exploratory analysis to identify potential biomarkers for the success of immunotherapy.

Patients and Methods

We retrospectively analyzed patients receiving CPI as a third-line treatment for advanced gastric cancer between January 2015 and March 2019. Clinicopathologic data, including patient characteristics, histopathologic reports, and treatment types and outcomes, were reviewed.

Results

Of the 74 patients included in this study, 45 (61%) received nivolumab and 29 (39%) received pembrolizumab as a third-line CPI. For second-line therapy, 41 patients (55%) were treated with ramucirumab plus a taxane, and 33 (45%) received a chemotherapy regimen without ramucirumab. The disease control rates of CPIs were not statistically different according to prior use of ramucirumab. The overall survival (OS) with CPI was higher in patients receiving second-line therapy without ramucirumab compared with those receiving ramucirumab and taxane (5.6 vs 4.8 months, HR 0.56, 95% confidence interval [CI] 0.33–0.96; p = 0.03); however, this was not significant in a multivariate analysis. Patients achieving a response to second-line ramucirumab and a taxane showed greater benefit from subsequent CPI treatment compared with those not achieving a response (median OS 9.9 vs 2.3 months, HR 0.20, 95% CI 0.07–0.54; p < 0.001) as found in an exploratory analysis. Multivariate analysis also showed that prior response to ramucirumab and a taxane was an independent prognostic factor of OS with third-line CPI.

Conclusions

Response to ramucirumab and a taxane as a second-line treatment is an important prognostic marker for OS with subsequent third-line CPI. This data might provide useful information when applying CPIs as third-line therapies in advanced gastric cancer patients.

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea

    Jinchul Kim, Seonggyu Byeon, Hyera Kim, Ja Hyun Yeo, Jung Yong Hong, Jeeyun Lee, Ho Yeong Lim, Won Ki Kang & Seung Tae Kim

  2. Department of Hematology‑Oncology, Inha University College of Medicine and Hospital, Inchon, Korea

    Jinchul Kim

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  1. Jinchul Kim
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  2. Seonggyu Byeon
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  3. Hyera Kim
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  4. Ja Hyun Yeo
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  5. Jung Yong Hong
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  7. Ho Yeong Lim
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  8. Won Ki Kang
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  9. Seung Tae Kim
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Correspondence to Seung Tae Kim.

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No external funding was used in the preparation of this manuscript.

Conflicts of interest

Jinchul Kim, Seonggyu Byeon, Hyera Kim, Ja Hyun Yeo, Jung Yong Hong, Jeeyun Lee, Ho Yeong Lim, Won Ki Kang, and Seung Tae Kim declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Kim, J., Byeon, S., Kim, H. et al. Impact of Prior Ramucirumab Use on Treatment Outcomes of Checkpoint Inhibitors in Advanced Gastric Cancer Patients. Targ Oncol 15, 203–209 (2020). https://doi.org/10.1007/s11523-020-00713-1

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  • DOI: https://doi.org/10.1007/s11523-020-00713-1

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