Analyzing The Use of Elacestrant in ESR1+ Advanced Breast Cancer

CASE SUMMARY

A 56-year-old, postmenopausal woman presented with a palpable right breast mass with no clinically abnormal axillary lymph nodes. Core biopsy showed the patient had grade II invasive ductal carcinoma (IDC), was estrogen receptor positive (ER+)/progesterone receptor positive (PR+) and had HER2 immunohistochemistry (IHC) of 0; Ki-67 was at 33%. Lumpectomy and sentinel lymph node (SLN) biopsy showed a 3.0 c grade 2 IDC, but 2 SLNs were negative for malignant cells. The patient had a 21-gene recurrence score of 27. She received docetaxel and cyclophosphamide for 4 cycles followed by radiation therapy and completed 5 years of adjuvant aromatase inhibitor (AI).

Three years after completion, she reported right-sided abdominal pain and mild nausea. A CT scan showed 3 suspicious liver lesions (right lobe, largest 2 cm) and a liver biopsy showed adenocarcinoma consistent with breast primary ER+/PR+, HER2 IHC 0. Her liver enzymes were normal and comprehensive molecular testing from the tissue biopsy showed no actionable alterations. AI plus palbociclib (Ibrance) was initiated. The therapy was tolerated well, with grade 2 neutropenia that did not require dose modification of palbociclib. Twenty months later, follow-up imaging showed increased size of both liver nodules and 2 new lung nodules, the largest measuring 0.9 cm. Her ECOG performance status is now 0, and liver enzymes are still normal.

DISCUSSION QUESTIONS

• Considering the EMERALD trial (NCT03778931) data on the duration of CDK4/6 inhibitor treatment, does it change your practice for the ESR1-mutated or the dual mutation ESR1/PI3K subgroups?
• How does the safety data from EMERALD compare with standard therapies used in the second line/third line setting, e.g., everolimus plus exemestane or alpelisib plus fulvestrant?​
• How do you manage endocrine therapy-related fatigue, gastrointestinal toxicity, and musculoskeletal pain for your patients? ​
• Do you consider prophylactic treatment for nausea and/or vomiting?

DAYA S. SHARMA, MD: I will use elacestrant [Orserdu] first.

KOMAL JHAVERI, MD: What about the safety data compared with the standard-of-care therapies used in the second line? Are any of you surprised with the [EMERLAD trial] safety data? Were you happy with the safety data?

Komal Jhaveri, MD

Section Head, Endocrine Therapy Research Program

Clinical Director, Early Drug Development Service

Patricia and James Cayne Chair for Junior Faculty

Memorial Sloan Kettering Cancer Center​

HARVINDER SINGH, MD: I think it's well tolerated compared with some of the other [therapies we use], including everolimus.¹

JHAVERI: Does it feel necessary to use prophylaxis for nausea or vomiting [always]? Or if its low-grade, would you feel you might be able to just [give a prophylaxis] on a case-by-case basis?

SINGH: I would think educating the patient and making sure they have the prescription is important so that they know it's an oral drug, but it could cause [nausea and vomiting]. Then, we need to make sure they have access [to a prophylaxis].

MAYER GOTBATY, MD: If you have a patient on a first-line AI CDK4/6-based therapy, and they progress in 3 months, are you trying a second-line hormonal therapy or going to chemotherapy?

JHAVERI: In [this scenario], in 3 months I would try chemotherapy. I'm not trying an endocrine-based therapy here because I am worried about primary endocrine resistance. I would do a biopsy in this case, and I would want to see if their tumor is truly ER positive, HER2-negative, and see if there is something different about this tumor. Was there an...alteration that could explain why the patient progressed so quickly? Regardless, I would be worried about primary endocrine resistance [in this case], so I would think about using chemotherapy.

DISCUSSION QUESTIONS

• How will you incorporate ESR1-mutation testing into treatment planning? ​
• How will you sequence therapies for this patient population?

JHAVERI: The rationale is, in my mind, physician driven because you will only be able to offer a treatment if you know the results of this [mutation testing], and you want to know the result post CDK4/6 therapy in order to decide whether you want to give this patient elacestrant...[or another therapy]. I think you want to know the testing result, so you are able to provide this biomarker-based recommendation.

[The key factor that drives any second-line treatment decision] is: Does the patient have any comorbidities that will get in the way of our treatment recommendation? This can include types of metastatic disease involvement, if we think they won't be adherent to the treatment, and also when their recurrence occurred, but all of these factors have to be taken into account when we're thinking about 2 or 3 treatment options that could be applicable for any given patient.

^Reference:

^{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}