481P - Second generation oral selective estrogen receptor degraders (SERDs) in breast cancer: A systematic review and meta-analysis of clinical trials

Background

SERDs are effective treatment options for breast cancer (BC) patients (pts) after progression on first-line therapy, especially for those harboring estrogen-receptor 1 (ESR1) mutations (mut). Several studies have explored the potential of SERDs to overcome endocrine resistance, yielding promising results.

Methods

We conducted a systematic review and meta-analysis to assess oral SERDs in hormone receptor-positive, HER-2-negative BC pts. Efficacy was evaluated by tumor response according to ESR1mut, and the number of pts with variant allele frequency (VAF) decreased with SERD therapy. We searched Pubmed, Scopus, and Cochrane Library databases and congress websites for randomized and non-randomized clinical trials. We used a random effects model for data pooling; heterogeneity was assessed with I² statistics.

Results

We included 19 studies with 1,798pts. Of 855 pts tested, 387 (45%) had ESR1mut. ESR1mut frequency and respective overall response rate (ORR) are described in the table. We found 80% of pts(95%CI 0.72-0.88 I²56%) had a decrease in VAF with SERD therapy. The estimated risk of all-causality adverse events (AE) was 86% (95% CI 0.80-0.92), and grades 3 or 4 AE were 19% (95% CI 0.11-0.28). SERD plus Palbociclib resulted in higher rates of AEs (p<0.01). Elacestrant had numerically higher G3-4 AEs compared to the other SERD (p=0.05). The most common AEs were nausea (35%), diarrhea (30%), and fatigue (23%). Arthralgia was reported in 15%, and only 1% of pts had to discontinue treatment due to AE.

Table: 481P

Characterization of ESR1mut and response to SERD (amcenestrant, elacestrant, and camizestrant)

Conclusions

Our study supports the favorable safety profile of the new generation oral SERD and presents its efficacy according to ESR1mut. Further studies shall assess the potential biomarker role of individual ESR1mut.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Goldner Cesca: Financial Interests, Personal, Invited Speaker: Novartis, Daiichi Sankyo, Zodic. All other authors have declared no conflicts of interest.