Abstract P3-11-04: Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials
Authors: Kroep Judith R , Charehbili Ayoub , Coleman Rob E , Aft Rebecca L , Hasegawa Yoshie , Liefers Gerrit-Jan , Winter Matthew C , Weilbaecher Katherine N , Akazawa Kohei , Hinsley Samantha , Putter Hein , Nortier Hans WR , Kohno Norio 
Published: May 2015

Background:

The addition of bisphosphonates to adjuvant systemic therapy reduces bone metastases and improves survival in postmenopausal patients with early breast cancer. We have conducted four randomised trials of neoadjuvant chemotherapy (CT) +/- zoledronic (ZA) in stage II/III breast cancer to investigate the potential for enhancing pathological response within the breast and axilla. We report here a meta-analysis of these studies to enable more reliable evaluation of treatment effects and investigate activity in pre-defined subgroups of interest.

Methods:

Individual patient data from four prospective randomized clinical trials reporting the effect of the addition of ZA on pathological response after neoadjuvant CT were pooled. Primary outcomes were pathological complete response in the breast (pCRb) and in the breast and lymph nodes (pCR). A fixed effects Mantel-Haenszel meta-analysis was performed using odds ratios (OR) from multivariate analyses in each study correcting for T-status and ER-status after testing for heterogeneity. Predefined subgroup analyses were performed for postmenopausal women and patients with triple-negative breast cancer.

Results:

pCRb and pCR data were available in 736 and 553 women respectively. A summary of results is shown in the table below. In the total study population, ZA addition to neoadjuvant CT did not increase pCRb/pCR rates (12.9% for CT only vs. 16.0% with CT+ ZA; OR 1.34, 95% C.I. 0.86-2.08). However, in postmenopausal women, the addition of ZA resulted in a doubling of the pCRb rate (8.5% for CT only vs. 17.0% with CT+ ZA; OR 2.72, 95% C.I. 1.15-6.42) and pCR rate (7.8% for CT only vs. 13.6% with CT+ ZA; OR 2.48, 95% C.I. 0.80-7.69). There was significant interaction between menopausal status and ZA benefit (P for interaction=0.047). In patients with triple-negative breast cancer a trend was observed favouring CT+ZA.

Pathological responseCTCT + ZAOdd's Ratio95% C.I.pCRb/totalPercentagepCRb/totalPercentagepCR in breastTotal population48/37312.958/36316.01.340.86-2.08Postmenopausal patients11/1308.524/14117.02.721.15-6.42*Pre/perimenopausal patients34/23214.733/21415.41.030.59-1.79Triple-negative breast cancer13/7018.621/6731.31.990.85-4.66pCR/totalPercentagepCR/totalPercentagepCR in breast and lymph nodesTotal population28/27910.033/27412.01.310.73-2.34Postmenopausal patients7/907.814/10313.62.480.80-7.69Pre/perimenopausal patients19/17810.718/16311.01.000.49-2.08Triple-negative breast cancer9/5217.315/5129.41.800.63-5.21Overview of pCRb and pCR in both treatment arms in the total population and predefined subgroups

Conclusion:

This meta-analysis shows that no overall benefit from the addition of ZA to neoadjuvant CT. However, as has been seen in the adjuvant setting, the addition of ZA to CT in postmenopausal women with early breast cancer appears to specifically increase the effects of CT with increases in pCRb and pCR. Further translational research is warranted to explore the mechanism of these observations and the potential treatment interaction with menopause.

Citation Format: Judith R Kroep, Ayoub Charehbili, Rob E Coleman, Rebecca L Aft, Yoshie Hasegawa, Gerrit-Jan Liefers, Matthew C Winter, Katherine N Weilbaecher, Kohei Akazawa, Samantha Hinsley, Hein Putter, Hans WR Nortier, Norio Kohno. Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-11-04.