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Depth of response predicts the clinical outcome of advanced HER2-positive gastric cancer to trastuzumab-based first-line chemotherapy

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Abstract

Purpose

Accumulating evidence suggests that response-related parameters such as depth of response (DpR) might be associated with survival in colorectal cancer, which has not been shown in gastric cancer. This study aimed to evaluate whether DpR was associated with clinical outcomes in HER2-positive AGC patients treated with trastuzumab-based chemotherapy.

Methods

Fifty-seven HER2-positive AGC patients who were treated with trastuzumab in combination with fluoropyrimidines plus cisplatin therapy as first-line treatment were retrospectively enrolled. DpR was defined as the percent maximal tumor shrinkage of target lesions observed at the lowest point compared with baseline. The cutoff DpR level to discriminate better survival was based on receiver-operating characteristic curve analysis. Association of DpR with progression-free survival (PFS) and overall survival (OS) was assessed using the multivariable Cox proportional hazards model.

Results

Median DpR level was 56.8% (range −37.9 to 100%). In multivariate models adjusted for relevant variables, DpR, as a dichotomized variable with a cutoff level of 50% and a continuous variable, was significantly associated with PFS (hazard ratio [HR] 0.39 and 0.97; 95% confidence interval [CI] 0.22–0.68 and 0.96–0.98) and OS (HR 0.38 and 0.98; 95% CI 0.21–0.70 and 0.97–0.99). Clinically meaningful differences in PFS (median, 9.8 vs. 4.1 months; p < 0.001) and OS (median, 24.7 vs. 12.8 months; p < 0.001) were observed between the high DpR (≥50%) and the low DpR groups (<50%).

Conclusions

Higher DpR predicted favorable outcomes following trastuzumab-based chemotherapy in HER2-positive AGC patients.

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Authors and Affiliations

  1. Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan

    Shigenori Kadowaki, Toshiki Masuishi, Yukiya Narita, Hiroya Taniguchi, Takashi Ura, Masashi Ando & Kei Muro

  2. Department of Gastroenterology, Tsuchiura Kyodo General Hospital, Tsuchiura, Ibaraki, Japan

    Tetsuya Eto

  3. Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan

    Masahiro Tajika & Yasumasa Niwa

  4. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan

    Yasushi Yatabe

Authors
  1. Shigenori Kadowaki
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  2. Toshiki Masuishi
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  3. Tetsuya Eto
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  4. Yukiya Narita
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  5. Hiroya Taniguchi
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  6. Takashi Ura
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  7. Masashi Ando
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  8. Masahiro Tajika
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  9. Yasumasa Niwa
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  10. Yasushi Yatabe
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  11. Kei Muro
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Corresponding author

Correspondence to Shigenori Kadowaki.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the ethics committees of Aichi Cancer Center Hospital and Tsuchiura Kyodo General Hospital and conducted in accordance with the 1964 Helsinki declaration and its later amendments. For this type of study, formal consent is not required.

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Kadowaki, S., Masuishi, T., Eto, T. et al. Depth of response predicts the clinical outcome of advanced HER2-positive gastric cancer to trastuzumab-based first-line chemotherapy. Cancer Chemother Pharmacol 80, 807–813 (2017). https://doi.org/10.1007/s00280-017-3422-6

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  • DOI: https://doi.org/10.1007/s00280-017-3422-6

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