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Basal biomarkers nestin and INPP4B predict gemcitabine benefit in metastatic breast cancer: Samples from the phase III SBG0102 clinical trial

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In a formal prospective-retrospective analysis of the phase III SBG0102 clinical trial randomizing metastatic breast cancer patients to gemcitabine-docetaxel or to single agent docetaxel, patients with basal-like tumors by PAM50 gene expression had significantly better overall survival in the gemcitabine arm. By immunohistochemistry (IHC), triple negative status was not predictive, but more specific biomarkers have since become available defining basal-like by nestin positivity or loss of inositol-polyphosphate-4-phosphate (INPP4B). Here, we evaluate their capacity to identify which patients benefit from gemcitabine in the metastatic setting. Nestin and INPP4B staining and interpretation followed published methods. A prespecified statistical plan evaluated the primary hypothesis that patients with basal-like breast cancer, defined as "nestin+ or INPP4B-", would have superior overall survival on gemcitabine-docetaxel when compared to docetaxel. Interaction tests, Kaplan-Meier curves and forest plots were used to assess prognostic and predictive capacities of biomarkers relative to treatment. Among 239 cases evaluable for our study, 36 (15%) had been classified as basal-like by PAM50. "Nestin+ or INPP4B-" was observed in 41 (17%) of the total cases and was significantly associated with PAM50 basal-like subtype. Within an estimated median follow-up of 13 years, patients assigned as IHC basal "nestin+ or INPP4B-" had significantly better overall survival on gemcitabine-docetaxel versus docetaxel monotherapy (HR = 0.31, 95%CI: 0.16-0.60), whereas no differences were observed for other patients (HR = 0.99), p-interaction<0.01. In the metastatic setting, women with IHC basal breast cancers defined as "nestin+ or INPP4B-" have superior overall survival when randomized to gemcitabine-containing chemotherapy compared to docetaxel alone. These findings need to be validated using larger prospective-retrospective phase III clinical trials series.

Original languageEnglish
JournalInternational Journal of Cancer
Volume144
Issue number10
Pages (from-to)2578-2586
Number of pages9
ISSN0020-7136
DOIs
Publication statusPublished - 2019

    Research areas

  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Biomarkers, Tumor/metabolism, Breast Neoplasms/drug therapy, Clinical Trials, Phase III as Topic, Deoxycytidine/analogs & derivatives, Disease-Free Survival, Docetaxel/therapeutic use, Female, Gene Expression Profiling/methods, Humans, Kaplan-Meier Estimate, Nestin/metabolism, Phosphoric Monoester Hydrolases/metabolism, Prognosis, Prospective Studies, Randomized Controlled Trials as Topic, Retrospective Studies

ID: 55905373