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Gastric cancer drug trials—are women second class citizens?

Nature Reviews Clinical Oncology volume 11, page 438 (2014)Cite this article

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I would like to thank Wang and colleagues for their comments (Gastric cancer drug trials—are women second class citizens? Nat. Rev. Clin. Oncol. doi:10.1038.nrclinonc.2013.231-c1)1 on the News & Views (Targeted therapies in gastric cancer—the dawn of a new era. Nat. Rev. Clin. Oncol. 11, 10–11; 2014),2 regarding the apparent limited activity of ramicirumab in women.

They question the lack of benefit of ramicirumab in this subgroup of patients, as suggested from the data reported in Figure 3 in the article by Fuchs et al.2 I believe that this observation illustrates one of the key limitations of subgroup analyses and multiple testing in trials. Phase III clinical trials are usually powered for a primary end point, such as overall survival, as noted in the REGARD study. However, additional patient and tumour characteristics are commonly evaluated individually to confirm broad applicability and for further hypothesis development. Multiple hypotheses testing in this regard is associated with a false discovery proportion, resulting in the possibility of identifying a difference that could also occur randomly.3,4 Specifically the Forest plot represented in Figure 3 reported the results of an analysis on 33 individual variables.2 At a 5% significance level, one would have expected at least one of these variables to suggest a false difference in efficacy.

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References

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  2. Fuchs, C. S. 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 383, 31–39 (2014).

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  1. Weill Cornell Medical Center, New York–Presbyterian Hospital, 1305 York Avenue, 12th Floor, New York, 10021, NY, USA

    Manish A. Shah

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Correspondence to Manish A. Shah.

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Shah, M. Gastric cancer drug trials—are women second class citizens?. Nat Rev Clin Oncol 11, 438 (2014). https://doi.org/10.1038/nrclinonc.2013.231-c2

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