Evaluating Elacestrant in the Management of ER-Positive, HER2-Negative Advanced Breast Cancer: Evidence to Date

Introduction

Approximately 288,000 new cases of invasive breast cancer are expected in the United States in 2022, and more than 43,000 women will die from breast cancer this year.1 Although breast cancer mortality has declined by 42% in the past 3 decades, breast cancer remains the second leading cause of cancer mortality in women.2 The most common subtype of breast cancer (approximately 75%) is the luminal subtype, defined by hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative status.3 Despite being the subtype with the best prognosis, distant recurrences in this biological group can occur more than 20 years after diagnosis.4

Endocrine therapy is the standard initial treatment for patients with metastatic breast cancers that are HR-positive, HER2-negative.5,6 Endocrine therapy includes drugs that act by inhibiting estrogen production, and agents that modulate estrogen receptor (ER) directly in cancer cells. Estrogen production can be inhibited by gonadotropin-releasing hormone agonists and by aromatase inhibitors (letrozole, anastrozole, and exemestane). Selective ER modulators (SERMs) include tamoxifen and toremifene. The ER antagonist fulvestrant acts by selectively degrading the ER in the cancer cells. Moreover, targeted agents, which include cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), everolimus, and alpelisib, can be used in addition to endocrine therapy drugs. Despite all these available agents, eventually all patients with advanced HR-positive breast cancer will experience disease progression due to endocrine therapy resistance.

Fulvestrant was approved by the US Food and Drug Administration (FDA) in 2002 and remained the only selective estrogen receptor degrader (SERD) approved for the treatment of advanced HR-positive breast cancer for more than 2 decades. Fulvestrant has been shown to improve overall survival as a single agent,7 and a 500 mg intramuscular monthly dose was found to be more effective than 250 mg (HR for overall survival of 0.81; 95% CI = 0.69 to 0.96; P = 0.02).8 In the past decade fulvestrant was also shown to be effective in combination with CDK4/6i.9–11 More recently, a Phase 3 clinical trial showed prolonged PFS with the addition of alpelisib to fulvestrant for patients with advanced disease and a PIK3CA mutation who had received previous endocrine therapy, with PFS of 11.0 months in the alpelisib-fulvestrant group, as compared with 5.7 months in the placebo-fulvestrant group (HR for progression or death, 0.65; 95% CI, 0.50 to 0.85; P<0.001).12

Mutations in the estrogen receptor gene α (ESR1) which encodes the ER have been associated with resistance to aromatase inhibitors in patients with advanced HR-positive breast cancer. These mutations can also cause partial resistance to tamoxifen and fulvestrant.13 There is also evidence that some patients have incomplete reduction in ER availability, which may correlate with progression of disease.14

The occurrence of resistance to currently approved endocrine therapy agents and the fact that fulvestrant requires intramuscular injections have led to an interest in agents with better bioavailability and more convenient administration. Elacestrant (RAD1901) is an oral nonsteroidal small-molecule SERD that selectively binds to the ER and activates its degradation.15 In this review, we will analyze the rationale for the use of elacestrant, the currently available data regarding efficacy and toxicity, and future directions.

Evidence to DatePreclinical Data

Wardell et al evaluated the pharmacological activities of elacestrant. The authors found that elacestrant inhibited ESR1 activation both in vitro and in vivo, inhibited breast cancer cell proliferation, and inhibited xenograft tumor growth.16

Garner et al demonstrated that elacestrant inhibits expression of ERα in cultured breast tumor cell lines, causing complete degradation of the ER. Elacestrant also inhibited proliferation of ER-positive MCF-7 cells in vitro and inhibited tumor growth in MCF-7 xenograft models. When compared to tamoxifen and fulvestrant, elacestrant led to greater tumor growth inhibition. Importantly, in a mouse xenograft model of brain metastasis, elacestrant prolonged survival in comparison to fulvestrant, as 41% (5/12) of these animals treated with elacestrant survived until the end of the study at day 54, whereas no animal in the fulvestrant group survived beyond day 34. In this study, elacestrant was well tolerated in mice, and protected against bone loss in ovariectomized rats. Elacestrant did not affect endometrial thickness and actually antagonized the effect of estradiol in the uterus. These data suggested that elacestrant has a possible agonist action in the bone and antagonist action in the uterus.15

In a preclinical study, Bihani et al evaluated the efficacy of elacestrant alone and in combination with palbociclib or everolimus in ER-positive breast cancer models. Elacestrant caused a similar degradation of ER than fulvestrant in cell lines in vitro, a decrease in progesterone receptor (PR) expression, and complete tumor growth inhibition at 4 weeks in an MCF7 xenograft model. When compared to elacestrant alone, the combination of elacestrant with palbociclib or everolimus resulted in greater tumor growth inhibition. In two patient-derived xenograft models harboring ESR1 mutations, elacestrant also inhibited tumor growth, and the inhibition was greater with the combination of elacestrant with palbociclib.17

Elacestrant was also evaluated in preclinical models of CDK4/6i resistance. Patel et al found that elacestrant inhibited growth in cells resistant to CDK4/6i, including in cells with ESR1 mutation. Elacestrant also inhibited tumor growth of xenografts derived from patients previously treated with a CDK4/6i or who had de novo resistance to CDK4/6i.18

These preclinical data provided rationale for testing elacestrant in clinical trials, either alone or in combination with other agents, in the treatment of advanced HR-positive breast cancer.

Clinical Trials

Several clinical studies have evaluated the use of elacestrant in advanced breast cancer (Table 1). A Phase 1b clinical trial (RAD1901-106) assessed the impact of elacestrant on the availability of ER in ER-positive breast cancer lesions using 16α-18F-fluoro-17β-estradiol positron emission tomography with low-dose computed tomography (FES-PET/CT). The trial included 16 post-menopausal women with advanced ER-positive, HER2-negative breast cancer who had disease progression after at least 6 months of 1–3 lines (median 2.5) of endocrine therapy for advanced disease. No patients had received prior CDK4/6i. Elacestrant was given continuously in two different doses, 400 mg daily or 200 mg daily, with escalation to 400 mg after 2 weeks. The median reduction in FES uptake in tumor lesions from baseline to day 14, which was the primary endpoint of the study, was 89.1%, and was similar in both dose cohorts. The overall objective response rate (ORR) was 11.1%, the time to response was 8 weeks, and the clinical benefit rate (CBR) was 30.8%. Median progression-free survival (PFS) was 5.3 months. Patients in the 400 mg cohort remained on elacestrant longer than patients who started at 200 mg and later escalated to 400 mg. The percentage change in FES uptake did not correlate with response, although it was a small number of patients. The trial also explored a potential correlation of response rates and ESR1 mutations in circulating tumor DNA (ctDNA); 56% of patients (N=9) had ESR1 mutations at baseline and the reduction of FES uptake was independent of the mutational status at baseline. The most common side effects were nausea (69%), fatigue (50%), dyspepsia (44%), and vomiting (37%).19

Table 1 Clinical Trials That Evaluated the Use of Elacestrant in Advanced Breast Cancer

The Phase I study RAD1901-005 evaluated the safety and antitumor activity of elacestrant in heavily pre-treated post-menopausal women with advanced ER-positive, HER2-negative breast cancer. A total of 57 patients with a median of 3 prior lines of therapy for advanced disease were enrolled to receive elacestrant as a single agent, with dose increments from 200 mg to 1000 mg. Of note, 52% of patients had received a prior SERD, 52% had received a prior CDK4/6i, and 50% of women had at least one ESR1 mutation at baseline ctDNA. The elacestrant dose selected for Phase II was 400 mg orally once a day, and a total of 50 patients were treated with this dose. The ORR was 19.4%, and the CBR was 42.6%; the median PFS was 4.5 months. The median time to response was 2 months, and the median duration of response was 5.8 months. The CBR in patients with an ESR1 mutation was 56.5%, and 30.4% in patients who had received prior CDK4/6i. Among patients with baseline ESR1 mutation and an available post-baseline blood sample, 82% had a reduction of mutant allele fraction at the end of cycle 1. The most frequent side effects were nausea, increase in triglycerides, and decrease in serum phosphorus levels. Gastrointestinal toxicity was less common with tablet than capsule formulation. There were no dose-limiting toxicities.20 This study provided preliminary evidence of clinical activity and rationale for phase III trials.

The EMERALD clinical trial was an international phase III open-label study comparing the safety and efficacy of elacestrant with standard of care endocrine therapy. The study included 477 men and post-menopausal women with locoregional recurrent or metastatic ER-positive, HER2-negative breast cancer who had received 1 or 2 lines of endocrine therapy for advanced disease. Previous treatment with a CDK4/6i was required, and no more than one prior line of chemotherapy for advanced disease was allowed. Patients were randomized to receive either elacestrant 400 mg daily or investigator’s choice endocrine treatment with fulvestrant or an aromatase inhibitor (anastrozole, letrozole or exemestane). The study protocol recommended that investigators choose fulvestrant if the patient had not yet received fulvestrant, and an aromatase inhibitor for the patients who had progressed on fulvestrant. Selection of aromatase inhibitor agent should take in consideration the prior therapy with aromatase inhibitor. Patients were stratified by ESR1 mutation detected in ctDNA using the Guardant360 CDx assay, prior treatment with fulvestrant, and presence or not of visceral metastasis. Primary endpoints were PFS in patients with ESR1 mutation and in all patients. Patients randomized to elacestrant received 400 mg orally once a day, and dose reductions to 300 mg or 200 mg daily were allowed if toxicity. A total of 43% of patients had received 2 prior lines of endocrine therapy for advanced disease, 48% had a detectable ESR1 mutation, and 29% of patients randomized to elacestrant had received prior fulvestrant. PFS was prolonged in the elacestrant arm versus standard of care in all patients, with a relative reduction in progression or death of 30% but an absolute difference in PFS of few weeks (HR 0.70; 95% CI, 0.55 to 0.88; P = 0.002; median PFS 2.8 months vs 1.9 months). PFS was also prolonged in patients with ESR1 mutation treated with elacestrant, with a relative reduction in progression or death of 45% (HR 0.55; 95% CI, 0.39 to 0.77; P = 0.0005; median PFS 3.8 months vs 1.9 months) comparing to standard of care. The 12-month PFS was 22.3% in patients treated with elacestrant versus 9.4% with standard of care, and in patients with ESR1 mutation it was 26.8% versus 8.2%, respectively. The authors also reported the benefit of elacestrant comparing to fulvestrant. Excluding patients who had received fulvestrant prior to the trial, the 12-month PFS was 22.3% with elacestrant versus 9.5% in the fulvestrant group. Among patients with ESR1 mutation, the 12-month PFS was 26.8% and 8.3% in the elacestrant versus fulvestrant group, respectively. Of note, subgroup analysis showed that elacestrant was also beneficial among patients who had received prior fulvestrant. Overall survival data was immature. The most common side effects were nausea, fatigue, vomiting, decreased appetite and arthralgia. Grade 3/4 adverse effects happened in 27% of patients receiving elacestrant, most commonly nausea, back pain and increased ALT, and in 20% of patients receiving standard of care therapy.21 Further data from the EMERALD trial demonstrated that the duration of prior CDK4/6i therapy was associated with PFS, and the longer the duration of prior CDK4/6i in the metastatic setting, the longer the PFS on elacestrant versus standard of care therapy. For patients that received at least 12 months of CDK4/6i, the median PFS was 3.8 months in the elacestrant group versus 1.9 months in the standard of care group (HR 0.61, 0.45–0.83). Of note, the difference was higher in patients with ESR1 mutations (median PFS in patients with ≥ 12 months prior CDK4/6i therapy of 8.6 months versus 1.9 months in patients treated with elacestrant versus standard of care, respectively; HR 0.41, 0.26–0.63).22 Based on the results of the EMERALD trial, on January 27, 2023, the FDA approved elacestrant for post-menopausal women and men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer who had disease progression following at least one line of endocrine therapy. The Guardant360 CDx assay was also approved by the FDA as a companion diagnostic device to identify patients for treatment with elacestrant.

Discussion

Preclinical evidence revealed that elacestrant was effective in decreasing ER-positive cell proliferation and tumor growth in xenograft models and in cells with ESR1 mutation or resistance to CDK4/6i.15–18 Both RAD1901-005 and RAD1901-106 studies confirmed elacestrant efficacy in the clinical setting, with impact in both ORR and CBR.19,20

Elacestrant was the first oral SERD to be shown to increase progression-free survival in patients with advanced HR-positive, HER2-negative breast cancer in a phase III trial, comparing to standard of care single-agent endocrine therapy. The EMERALD trial design was innovative due to the inclusion of ESR1 mutation as a stratification factor. The trial demonstrated that elacestrant was more beneficial for patients whose tumors harbored an ESR1 mutation compared to fulvestrant, leading to the approval by the FDA in this patient population. However, it should be noted that the study showed a short PFS in the overall population and in patients with ESR1 mutations, irrespective of treatment arm, recognizing that these were patients previously treated with CDK4/6i. Taking into account that some patients in this trial could already have resistance to endocrine therapy, the authors also reported the 6-month and 12-month PFS rates, which highlighted the benefit of elacestrant.21 Although elacestrant was beneficial regardless of the duration of prior exposure to CDK4/6i in the EMERALD trial, patients who received prior CDK4/6i for a longer period of time seemed to benefit more from elacestrant.22

Elacestrant was generally well tolerated at a dose of 400 mg daily in clinical trials, with the main side effects being upper gastrointestinal symptoms and fatigue.19–21 In the RAD1901-106 trial, patients treated with 200 mg daily dose of elacestrant also had a significant reduction in FES uptake, suggesting that 200 mg doses may be an option for patients who do not tolerate 400 mg.19

The currently available data on elacestrant use in the treatment of patients with advanced breast cancer provided rationale for the development of multiple other clinical trials investigating the use of elacestrant in early-stage breast cancer, and in combination with other drugs for metastatic disease, including alpelisib, everolimus, and CDK4/6i (Table 2).23–27 Although pre-menopausal women were not eligible for the RAD1901-106, RAD1901-005, and EMERALD trials, some of the new clinical protocols are enrolling pre-menopausal women and combining elacestrant with ovarian suppression.24–26 Trials comparing elacestrant versus fulvestrant as the backbone endocrine therapy in combination with CDK4/6i, alpelisib, and everolimus will help guide clinical decision-making regarding the SERD of choice in second-line therapy. When choosing second- or third-line therapy for advanced HR-positive, HER2-negative patients, the cost will also have to be taken into consideration as elacestrant reached the market at a much higher price than aromatase inhibitors and fulvestrant.

Table 2 Ongoing Clinical Trials Examining the Use of Elacestrant in Breast Cancer

Several other oral SERDs have been shown to have preclinical efficacy in HR-positive breast cancer, including amcenestrant, giredestrant, imlunestrant, camizestrant, and rintodestrant, among others. These drugs are currently undergoing investigation into the treatment of HR-positive breast cancer patients, both in early-stage and metastatic settings.28

Amcenestrant (SAR439859) was tested in a single-arm phase I/II trial (AMEERA-1) as monotherapy in post-menopausal women with pre-treated ER-positive, HER2-negative advanced breast cancer. ORR was 11%, and CBR was 28%, and amcenestrant also demonstrated efficacy among patients with ESR1 mutations. There were no dose-limiting toxicities, and the most common treatment-related adverse effect was gastrointestinal symptoms, hot flashes, and arthralgia.29 In the phase II randomized clinical trial AMEERA-3 of amcenestrant compared with standard endocrine therapy of physician’s choice in pre-treated patients, however, amcenestrant failed to improve PFS, the primary endpoint of the study.30 Giredestrant (GDC-9545), another oral SERD, failed to improve PFS when compared to aromatase inhibitor or fulvestrant in pre-treated men and women with advanced breast cancer in the phase II acelERA BC study.31

Imlunestrant (LY3484356) has also been shown to have activity in pre-treated pre- and post-menopausal patients with advanced breast cancer in the phase Ia EMBER trial, without dose limiting toxicities.32 Rintodestrant (G1T48) was tested in a phase I trial in pre-treated ER-positive, HER2-negative advanced breast cancer patients that had not received a CDK4/6i, and was found to be effective, including in patients with ESR1 mutations.33

In the phase I clinical trial SERENA-1 evaluating camizestrant (AZD9833) in pre-treated patients with advanced ER-positive, HER2-negative breast cancer, the main adverse effects were visual disturbances, bradycardia, and nausea. In that trial, camizestrant had an ORR of 16% and CBR of 42%.34 The SERENA-2 trial evaluated the efficacy and safety of different camizestrant doses as monotherapy in comparison with fulvestrant in 240 patients with ER-positive and HER2-negative advanced breast cancer. Patients should have received no more than one line of endocrine therapy and no more than one line of chemotherapy in an advanced setting. Approximately 50% of patients had received a prior CDK4/6i, and ESR1 mutation was present in 36.7% of patients. Camizestrant increased PFS comparing to fulvestrant, with median PFS of 7.2 months with camizestrant 75 mg, 7.7 months with camizestrant 150 mg, and 3.7 months with fulvestrant (HR 0.58, CI 0.41–0.81, p = 0.0124, and HR 0.67, CI 0.48–0.92, p = 0.0161, respectively). Camizestrant also increased PFS in patients with prior exposure to CDK4/6i. In patients with an ESR1 mutation, the median PFS was 6.3 months with camizestrant 75 mg, 9.2 months with camizestrant 150 mg, and 2.2 months with fulvestrant (HR 0.33, CI 0.18–0.58, and HR 0.55, CI 0.33–0.89, respectively). Both camizestrant doses were well tolerated.35

Several of these oral SERDs are being tested in combination with CDK4/6i, alpelisib, and everolimus in ongoing phase III clinical trials for advanced breast cancer. These drugs are also undergoing investigation in early-stage disease in neoadjuvant and adjuvant settings.28 At the moment, there are no head-to-head comparison studies of elacestrant with other oral SERDs.

Conclusion

Elacestrant was the first oral SERD to improve PFS in previously treated patients with HR-positive, HER2-negative advanced breast cancer when compared to standard of care endocrine therapy. Importantly, it was more beneficial in patients with ESR1 mutation, a known mechanism of resistance to therapy to aromatase inhibitors, leading to FDA approval in this patient population. Ongoing clinical trials evaluating elacestrant and other SERDs will provide data that may assist clinicians decide the best choice and sequence of endocrine therapy agents for HR-positive breast cancer.

Disclosure

Dr Massimo Cristofanilli reports personal fees from Pfizer, AstraZeneca US, Menarini, and Lilly; non-financial support from Olaris and Syantra; grants from Celcuity, during the conduct of the study. The authors report no other conflicts of interest in this work.

References

1. Giaquinto AN, Sung H, Miller KD, et al. Breast cancer statistics, 2022. CA Cancer J Clin. 2022. doi:10.3322/caac.21754

2. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7–33. doi:10.3322/caac.21708

3. Hwang KT, Kim J, Jung J, et al. Impact of breast cancer subtypes on prognosis of women with operable invasive breast cancer: a population-based study using SEER database. Clin Cancer Res. 2019;25(6):1970–1979. doi:10.1158/1078-0432.CCR-18-2782

4. Pan H, Gray R, Braybrooke J; for EBCTCG. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836–1846. doi:10.1056/NEJMoa1701830

5. Burstein HJ, Somerfield MR, Barton DL, et al. Endocrine treatment and targeted therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: ASCO guideline update. J Clin Oncol. 2021;39(35):3959–3977. doi:10.1200/JCO.21.01392

6. Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020;31(12):1623–1649. doi:10.1016/j.annonc.2020.09.010

7. Howell A, Pippen J, Elledge RM, et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma: a prospectively planned combined survival analysis of two multicenter trials. Cancer. 2005;104(2):236–239. doi:10.1002/cncr.21163

8. Di Leo A, Jerusalem G, Petruzelka L, et al. Final overall survival: fulvestrant 500 mg vs 250 mg in the randomized CONFIRM trial. J Natl Cancer Inst. 2014;106(1):djt337. doi:10.1093/jnci/djt337

9. Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016;17(4):425–439. doi:10.1016/S1470-2045(15)00613-0

10. Slamon DJ, Neven P, Chia S, et al. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol. 2018;36(24):2465–2472. doi:10.1200/JCO.2018.78.9909

11. Sledge GW, Toi M, Neven P, et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2-negative breast cancer that progressed on endocrine therapy-MONARCH 2: a randomized clinical trial. JAMA Oncol. 2020;6(1):116–124. doi:10.1001/jamaoncol.2019.4782

12. André F, Ciruelos E, Rubovszky G, et al.; for SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019;380(20):1929–1940. doi:10.1056/NEJMoa1813904

13. Jeselsohn R, Buchwalter G, De Angelis C, Brown M, Schiff R. ESR1 mutations—a mechanism for acquired endocrine resistance in breast cancer. Nat Rev Clin Oncol. 2015;12(10):573–583. doi:10.1038/nrclinonc.2015.117

14. van Kruchten M, de Vries EG, Glaudemans AW, et al. Measuring residual estrogen receptor availability during fulvestrant therapy in patients with metastatic breast cancer. Cancer Discov. 2015;5(1):72–81. doi:10.1158/2159-8290.CD-14-0697

15. Garner F, Shomali M, Paquin D, Lyttle CR, Hattersley G. RAD1901: a novel, orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models. Anticancer Drugs. 2015;26(9):948–956. doi:10.1097/CAD.0000000000000271

16. Wardell SE, Nelson ER, Chao CA, Alley HM, McDonnell DP. Evaluation of the pharmacological activities of RAD1901, a selective estrogen receptor degrader. Endocr Relat Cancer. 2015;22(5):713–724. doi:10.1530/ERC-15-0287

17. Bihani T, Patel HK, Arlt H, et al. Elacestrant (RAD1901), a selective estrogen receptor degrader (SERD), has antitumor activity in multiple ER+ breast cancer patient-derived xenograft models. Clin Cancer Res. 2017;23(16):4793–4804. doi:10.1158/1078-0432.CCR-16-2561

18. Patel HK, Tao N, Lee KM, et al. Elacestrant (RAD1901) exhibits anti-tumor activity in multiple ER+ breast cancer models resistant to CDK4/6 inhibitors. Breast Cancer Res. 2019;21(1):146. doi:10.1186/s13058-019-1230-0

19. Jager A, de Vries EGE, der Houven van Oordt CWM, et al. A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imaging. Breast Cancer Res. 2020;22(1):97. doi:10.1186/s13058-020-01333-3

20. Bardia A, Kaklamani V, Wilks S, et al. Phase I study of elacestrant (RAD1901), a novel selective estrogen receptor degrader, in ER-positive, HER2-negative advanced breast cancer. J Clin Oncol. 2021;39(12):1360–1370. doi:10.1200/JCO.20.02272

21. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol. 2022;40(28):3246–3256. doi:10.1200/JCO.22.00338

22. Bardia A, Bidard FC, Neven P, et al. EMERALD phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+/HER2- metastatic breast cancer: updated results by duration of prior CDK4/6i in metastatic setting. Presented at SABCS 2022; Abstract GS3-01. December6-10, 2022.

23. Elacestrant in preoperative setting, a window of opportunity study (ELIPSE). Clinical Trial Identifier NCT04797728. Available from: https://clinicaltrials.gov/ct2/show/NCT04797728. Accessed November24, 2022.

24. Elacestrant for treating ER+/HER2- breast cancer patients with ctDNA relapse (EORTC-2129-BCG). Clinical Trial Identifier NCT05512364. Available from: https://clinicaltrials.gov/ct2/show/NCT05512364. Accessed November24, 2022.

25. An open-label multicenter phase 1b-2 study of elacestrant as monotherapy and in combination with abemaciclib in women and men with brain metastasis from estrogen receptor positive, HER-2 negative breast cancer (ELECTRA). Clinical Trial Identifier NCT05386108. Available from: https://clinicaltrials.gov/ct2/show/NCT05386108. Accessed November24, 2022.

26. A phase 1b/2, open-label umbrella study to evaluate safety and efficacy of elacestrant in various combination in patients with metastatic breast cancer (ELEVATE). Clinical Trial Identifier NCT05563220. Available from: https://clinicaltrials.gov/ct2/show/NCT05563220. Accessed November24, 2022.

27. Multicenter open label phase Ib/II trial of abemaciclib and elacestrant in patients with brain metastasis due to HR+/Her2- breast cancer. Clinical Trial Identifier NCT04791384. Available from: https://clinicaltrials.gov/ct2/show/NCT04791384. Accessed November24, 2022.

28. Lloyd MR, Wander SA, Hamilton E, Razavi P, Bardia A. Next-generation selective estrogen receptor degraders and other novel endocrine therapies for management of metastatic hormone receptor-positive breast cancer: current and emerging role. Ther Adv Med Oncol. 2022;14:17588359221113694. doi:10.1177/17588359221113694

29. Bardia A, Chandarlapaty S, Linden HM, et al. AMEERA-1 phase 1/2 study of amcenestrant, SAR439859, in postmenopausal women with ER-positive/HER2-negative advanced breast cancer. Nat Commun. 2022;13(1):4116. doi:10.1038/s41467-022-31668-8

30. Tolaney SM, Chan A, Petrakova K, et al. AMEERA-3, a phase II study of amcenestrant (AMC) versus endocrine treatment of physician’s choice (TPC) in patients (pts) with endocrine-resistant ER+/HER2− advanced breast cancer (aBC). Ann Oncol. 2022;33(suppl_7):S88–S121. doi:10.1016/annonc/annonc1040

31. Martin Jimenez M, Lim E, Chavez-Mac Gregor M, et al. Giredestrant (GDC-9545) vs physician choice of endocrine monotherapy (PCET) in patients (pts) with ER+, HER2– locally advanced/metastatic breast cancer (LA/mBC): primary analysis of the Phase II, randomised, open-label acelERA BC study. Ann Oncol. 2022;33(suppl_7):S88–S121. doi:10.1016/annonc/annonc1040

32. Jhaveri K, Lim E, Hamilton E, et al. A first-in-human phase 1a/b trial of LY3484356, an oral selective estrogen receptor (ER) degrader (SERD) in ER+ advanced breast cancer (aBC) and endometrial endometrioid cancer (EEC): results from the EMBER study. J Clin Oncol. 2021;39(15_suppl):1050. doi:10.1200/JCO.2021.39.15_suppl.1050

33. Maglakelidze M, Bulat I, Ryspayeva D, et al. Rintodestrant (G1T48), an oral selective estrogen receptor degrader, in combination with palbociclib for ER+/HER2– advanced breast cancer: phase 1 results. J Clin Oncol. 2021;39(15_suppl):1063. doi:10.1200/JCO.2021.39.15_suppl.1063

34. Hamilton E, Oliveira M, Banerji U, et al. A phase I dose escalation and expansion study of the next generation oral SERD AZD9833 in women with ER-positive, HER2-negative advanced breast cancer. J Clin Oncol. 2020;38(15_suppl):1024. doi:10.1200/JCO.2020.38.15_suppl.1024

35. Oliveira M, Pominchuk D, Nowecki Z, et al. Camizestrant, a next generation oral SERD vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: results of the randomized, multi-dose Phase 2 SERENA-2 trial. 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas; abstract GS3-02. Accessed December8, 2022.

留言 (0)

沒有登入
gif