Abstract P2-12-02: Cochrane review of capecitabine for hormone receptor positive versus hormone receptor negative breast cancer
Authors: Redfern A , Lau P , White A , Hoon S , Bulsara M , Long A 
Published: March 2017

Capecitabine is an oral fluoropyramidine prodrug which may have differential efficacy in hormone receptor (HR) positive and HR negative breast cancer. We conducted a systematic review of randomised control trials (RCT) comparing chemotherapy regimens with or without capecitabine in HR positive and HR negative breast cancer.

Methods

This review was conducted by standard Cochrane review procedures. Our protocol has been published previously. We conducted a comprehensive literature search including MEDLINE, EMBASE, CENTRAL databases, clinical trial registries and major oncology conferences for capecitabine RCTs. 1913 references were identified with 209 suitable for detailed review. 62 RCTs (40 metastatic, 13 adjuvant, 9 neoadjuvant) comparing chemotherapy regimens with or without capecitabine were identified. 21 studies (10 metastatic, 7 adjuvant, 4 neoadjuvant) reporting outcome data by HR status proceeded to full data extraction. 2 studies reported comprehensive outcome data by HR status, the remainder reporting by hazard or odds ratios only.

Results

In metastatic trials, capecitabine significantly improved outcomes for HR positive but not HR negative disease for chemotherapy alone (SO14999 trial – odds ratio (OR) for OS 0.65 (95% CI 0.47-0.89) v 0.90 (0.65-1.24) and possibly with additional trastuzumab (CHAT trial – OR for PFS 0.61 v 0.87 (significance not reported)). Significant benefit was seen for adding capecitabine to bevacizumab after taxane completion only in HR positive disease (IMELDA trial – OR for PFS 0.33 (0.22-0.50) v 0.70 (0.39-1.25)). In contrast, adding capecitabine to a taxane with bevacizumab showed the reverse with only HR negative patients benefiting (TABEA trial – OR for PFS 1.49 (0.99-2,24) v 0.51 (0.269-0.959)).

Adjuvant trials investigating the addition of capecitabine to anthracycline-taxane containing regimens or as monotherapy in elderly patients. Preliminary analysis indicates HR negative cancers benefit from the addition of capecitabine compared to non-capecitabine containing regimens. No observed benefit in HR positive disease with the addition of capecitabine was been demonstrated.

Odds ratio for outcomes by the addition of capecitabine to adjuvant chemotherapyOutcomeNo. trialsHR GroupOR95% CIp valueDFS6All0.920.83-1.020.11 5HR positive1.050.91-1.220.50 4HR negative0.720.58-0.880.002RFS1All0.880.71-1.090.07 1HR positive0.990.77-1.270.94 2HR negative0.630.46-0.870.005OS6All0.900.80-1.030.12 1HR positive0.710.45-1.120.14 1HR negative0.640.44-0.930.02

Neoadjuvant trials investigating the utility of capecitabine to anthracycline-taxane containing regimens showed no additional benefit with respect to pCR. Meta-analysis of response rates for all patients and differentiated by HR status showed no significant difference on inclusion of capecitabine.

Conclusion

In summary, metastatic and neoadjuvant trials did not show clear differential benefit of capecitabine in HR positive versus HR negative breast cancer. HR positive tumours in the metastatic setting might be more responsive to capecitabine. Additional benefit to an anthracycline-taxane containing regimens with capecitabine in the adjuvant setting was confined to HR negative cancers. Final results of our analysis will be presented.

Citation Format: Redfern A, Lau P, White A, Hoon S, Bulsara M, Long A. Cochrane review of capecitabine for hormone receptor positive versus hormone receptor negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-12-02.