Abstract P1-16-01: Efficacy of endocrine- versus chemotherapy-based treatments in hormone receptor-positive (HR+ve), HER2-negative (HER2-ve) postmenopausal metastatic breast cancer (mBC): A network meta-analysis (NMA)
Authors: Schettini F , Giuliano M , Rognoni C , De Placido S , Arpino G , Milani M , Giordano A , Cristofanilli M , Jerusalem G , Bachelot T , Pistilli B , De Laurentiis M , Venturini S , Generali D 
Published: May 2019

Background: The international guidelines support upfront use of endocrine therapies (HT), with or without new targeted agents (TA), in HR+ve/HER2-ve mBC. However, routine administration of regimens containing chemotherapy (CT) is still common, even in the absence of visceral crisis. Unfortunately, robust data from head-to-head direct comparisons among CT and HT-based strategies are still not available; therefore, a NMA is now the only valuable methodological approach to compare the efficacy and activity of HT- versus CT-based regimens, and to drive adequate suggestions for a potential therapeutic algorithm in 1stand 2ndline HR+ve/HER2-ve mBC.

Methods: We performed a systematic literature search and selected all available phase II-III RCT published between January 2000 and December 2017, which evaluated CT or HT ± TA as 1stand/or 2nd line treatments for postmenopausal women with HR+ve/HER2-ve mBC. Primary endpoint was progression-free survival (PFS)/time to tumor progression (TTP); secondary endpoint was overall response rate (ORR). A Bayesian NMA was generated to compare posterior median hazard ratios (HR) for PFS and odds ratios (OR) for ORR. The aromatase inhibitor (AI) anastrozole (ana) was chosen as the common comparator for the overall analyses, being the most frequent treatment in the dataset.

Results: A total of 137 eligible trials (48,653 patients) were included in the NMA. Among the regimens approved for clinical use, palbociclib (palbo) + letrozole (let) [HR:0.42, 95% credible intervals (CI):0.27-0.65], ribociclib (ribo) + let (HR:0.43, 95%CI:0.27-0.74), abemaciclib (abe) + ana/let (HR:0.42, 95%CI:0.25-0.71), palbo + fulvestrant (ful) (HR:0.37, 95%CI:0.25-0.55), abe + ful (HR:0.45, 95%CI:0.30-0.65), everolimus (eve) + exemestane (exe) (HR:0.37, 95%CI:0.25-0.54), and ful alone (HR:0.81, 95%CI:0.66-0.98) were significantly superior to ana in terms of PFS/TTP. Conversely, none of the CT-based regimens (i.e. paclitaxel±bevacizumab, anthracycline-based schemes, capecitabine, eribulin) was significantly superior to ana. Additionally, head-to-head comparisons among the CDK 4/6 inhibitors (CDK4/6i) combined with AI showed no significant difference (palbo + let vs. ribo + let, HR:0.98, 95%CI:0.63-1.54; palbo + let vs. abe + ana/let, HR:1.02, 95%CI:0.63-1.60; ribo + let vs. abe + ana/let, HR:1.03, 95%CI:0.62-1.73). On the other hand, CDK4/6i+AI were significantly superior to many 1stline CT, including taxane- and/or anthracycline-based regimens. Interestingly, no CT±TA regimen was significantly superior to ana or to HT+TA, in terms of ORR.

Conclusions: Our analysis suggests that CT-based regimens are not significantly superior to HT-based therapies as 1st/2ndline treatments for postmenopausal HR+ve/HER2-ve mBC. Instead, HT+TA, including CDK 4/6i and eve, were significantly superior to HT alone and to many 1st/2ndline CT regimens. Moreover, the three CDK4/6i combined with AI did not differ significantly among each other. These data strongly support the combination of a CDK 4/6i along with HT as the preferred first choice of treatment for the 1stand 2ndline in HR+ve/HER2-ve mBC, as indicated in all the international guidelines.

Citation Format: Schettini F, Giuliano M, Rognoni C, De Placido S, Arpino G, Milani M, Giordano A, Cristofanilli M, Jerusalem G, Bachelot T, Pistilli B, De Laurentiis M, Venturini S, Generali D. Efficacy of endocrine- versus chemotherapy-based treatments in hormone receptor-positive (HR+ve), HER2-negative (HER2-ve) postmenopausal metastatic breast cancer (mBC): A network meta-analysis (NMA) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-16-01.