Abstract 220P
Background
Oral selective estrogen receptor degraders (SERDs) are a promising treatment after disease progression on first-line endocrine therapy (ET) for hormone receptor-positive (HR+), HER2 negative advanced breast cancer (aBC) patients. This systematic review and meta-analysis of randomized clinical trials (RCTs) aimed to assess the efficacy of oral SERDS versus standard of care (SOC) ET according to ESR1 mutation (ESR1mut).
Methods
We searched PubMed, Embase, Cochrane, Web of Science, and congresses websites (ASCO and ESMO) for RCTs including HR+/HER2 negative aBC patients who were randomized to oral SERDs versus SOC ET and had received at least one prior line of ET. Outcomes of interest were progression-free survival (PFS) according to ESR1mut and objective response (ORR). Heterogeneity was evaluated with I2 statistics, and random-effect models were fitted.
Results
Of 519 studies screened, four RCTs were included, comprising 1290 patients, of whom; 41% harbored ESR1mut, 92.5% were postmenopausal, and 66% had visceral metastasis. Prior treatment for aBC included iCDK4/6 (73.3%), chemotherapy (21.6%), and; 25.2% of patients received ≥ two prior ET. In a pooled analysis, oral SERDs significantly improved PFS compared to SOC ET (HR 0.76 [95% CI 0.63-0.93 p=0.007]). ESR1mut patients treated with SERDs achieved a significant prolonged PFS than SOC ET (HR 0.59 [95% CI 0.45-0.77 p<0.001]), which was not seen in the wild-type ESR1 group (HR 0.84 [95%CI 0.67-1.04 p=0.11]). ORR was 11% in patients treated with SERDs and 7.4% in SOC ET (p=0,06). Table: 220P
| Trial | Phase | N | Follow-up Median, months | Oral SERD (N) | SOC ET (N) | ESR1mut |
| Bidard, 2022 | III | 477 | 15.1 | Elacestrant (239) | Fulvestrant, AI (238) | 228 |
| Oliveira, 2022 | II | 147 | 16.6 | Arm 1: camizestrant 75mg (74) | Fulvestrant (73) | 88 |
| 146 | Arm 2: camizestrant 150mg (73) | 88 | ||||
| Tonaley, 2022 | II | 290 | NA | Amcenestrant (143) | Fulvestrant, AI, tamoxifen (147) | 120 |
| Jimenez, 2022 | II | 303 | 7.89 | Giredestrant (151) | Fulvestrant, AI (152) | 90 |
N: number; SERD: Selective Estrogen Receptor Degrader; SOC: standard of care; ET: endocrine therapy; mut: mutant; NA: not available.
Conclusions
Oral SERDs improved PFS compared to SOC ET for ESR1mut HR+/HER2 negative metastatic breast cancer, but not for unselected patients.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Lobo: Financial Interests, Personal, Invited Speaker: MSD, Novartis. S.M. Sanches: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Daiichi Sankyo. M.G. Cesca: Financial Interests, Personal, Invited Speaker: Novartis, Zodiac, Daiichi; Financial Interests, Personal, Principal Investigator: AstraZeneca, Sanofi, Seagen. All other authors have declared no conflicts of interest.