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Journal of Clinical Oncology logoLink to Journal of Clinical Oncology
letter
. 2016 Aug 15;34(31):3823. doi: 10.1200/JCO.2016.68.8663

Is Treatment-Emergent Toxicity a Biomarker of Efficacy of Apatinib in Gastric Cancer?

Hyo Jin Lee 1,, Ji Young Moon 1, Seung Woo Baek 1
PMCID: PMC5477921  PMID: 27528729

To the Editor:

Li et al1 reported the results of a randomized, double-blind, placebo-controlled phase III trial of apatinib, which showed significant survival benefits in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. These results validate the role of vascular endothelial growth factor receptor (VEGFR) -2 signaling as an important therapeutic target; however, the clinical effects of apatinib are modest, with limited survival prolongation compared with placebo—median overall survival, 6.5 months versus 4.7 months; median progression-free survival, 2.6 months versus 1.8 months, respectively—and a low objective response rate of 1.70% as assessed by an independent response evaluation committee.1 Therefore, it is critically challenging to identify suitable predictive biomarkers that could be used to select patients who will benefit most from VEGFR-2 signal-inhibiting agents, such as apatinib, which would thereby improve efficacy and avoid unnecessary toxicity and high cost. These biomarkers might come from the cellular or molecular level using biospecimens collected from patients. Alternatively, occurrence of adverse events might act as surrogate biomarkers of drug activity, enabling the prediction of outcome during treatment because the occurrence of treatment-emergent toxic effects is associated with a pharmacodynamic effect of the drug.2-4 Recently, it has been suggested that the occurrence of specific adverse events, such as hypertension, hand-foot syndrome, and proteinuria, during antiangiogenic therapy might be associated with improved efficacy.4-7 Regarding apatinib, in particular, it was reported that hypertension and hand-foot skin reaction were significantly related to longer progression-free and overall survival in patients with advanced breast cancer.8 Therefore, it would be interesting to know whether the prospective data set reported by Li et al1 shows that the development of treatment-specific adverse effects, such as hypertension, hand-foot syndrome, and proteinuria, is related to treatment outcome.

The investigators could help to address this issue by analyzing survival data according to the emergence of treatment-related adverse events. Such data could help clinicians make better treatment decisions and may shed light on the future development of VEGFR signaling-targeted therapy for gastric and gastroesophageal junction carcinomas.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Is Treatment-Emergent Toxicity a Biomarker of Efficacy of Apatinib in Gastric Cancer?

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc.

Hyo Jin Lee

No relationship to disclose

Ji Young Moon

No relationship to disclose

Seung Woo Baek

No relationship to disclose

REFERENCES

  • 1.Li J, Qin S, Xu J, et al. Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol. 2016;34:1448–1454. doi: 10.1200/JCO.2015.63.5995. [DOI] [PubMed] [Google Scholar]
  • 2.Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): An international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31–39. doi: 10.1016/S0140-6736(13)61719-5. [DOI] [PubMed] [Google Scholar]
  • 3.Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): A multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384:665–673. doi: 10.1016/S0140-6736(14)60845-X. [DOI] [PubMed] [Google Scholar]
  • 4.Dienstmann R, Braña I, Rodon J, et al. Toxicity as a biomarker of efficacy of molecular targeted therapies: Focus on EGFR and VEGF inhibiting anticancer drugs. Oncologist. 2011;16:1729–1740. doi: 10.1634/theoncologist.2011-0163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Horsley L, Marti K, Jayson GC. Is the toxicity of anti-angiogenic drugs predictive of outcome? A review of hypertension and proteinuria as biomarkers of response to anti-angiogenic therapy. Expert Opin Drug Metab Toxicol. 2012;8:283–293. doi: 10.1517/17425255.2012.656845. [DOI] [PubMed] [Google Scholar]
  • 6.Ravaud A, Schmidinger M. Clinical biomarkers of response in advanced renal cell carcinoma. Ann Oncol. 2013;24:2935–2942. doi: 10.1093/annonc/mdt288. [DOI] [PubMed] [Google Scholar]
  • 7.Hamnvik OP, Choueiri TK, Turchin A, et al. Clinical risk factors for the development of hypertension in patients treated with inhibitors of the VEGF signaling pathway. Cancer. 2015;121:311–319. doi: 10.1002/cncr.28972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Fan M, Zhang J, Wang Z, et al. Phosphorylated VEGFR2 and hypertension: Potential biomarkers to indicate VEGF-dependency of advanced breast cancer in anti-angiogenic therapy. Breast Cancer Res Treat. 2014;143:141–151. doi: 10.1007/s10549-013-2793-6. [DOI] [PubMed] [Google Scholar]

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