Abemaciclib Plus Fulvestrant in Advanced Breast Cancer After Progression on CDK4/6 Inhibition: Results From the Phase III postMONARCH Trial
Yet another combination to consider after CDK4/6i + ET in HR+ MBC!
Alternative dosing of exemestane given TIW vs. once weekly treatment in adjuvant breast cancer, end-point was serum estradiol measurements and not survival metrics. Would like to see this done on a larger scale or with other end-points, but for those who are not tolerating standard dosing, this could be an option to consider.
Successful therapeutic cancer prevention requires definition of the minimal effective dose. Aromatase inhibitors decrease breast cancer incidence in high-risk women, but use in prevention and compliance in adjuvant settings are hampered by adverse events.
To compare the noninferiority percentage change of estradiol in postmenopausal women with estrogen receptor–positive breast cancer given exemestane, 25 mg, 3 times weekly or once weekly vs a standard daily dose with a noninferiority margin of −6%.
This multicenter, presurgical, double-blind phase 2b randomized clinical trial evaluated 2 alternative dosing schedules of exemestane. Postmenopausal women with estrogen receptor–positive breast cancer who were candidates for breast surgery were screened from February 1, 2017, to August 31, 2019. Blood samples were collected at baseline and final visit; tissue biomarker changes were assessed from diagnostic biopsy and surgical specimen. Biomarkers were measured in different laboratories between April 2020 and December 2021.
Exemestane, 25 mg, once daily, 3 times weekly, or once weekly for 4 to 6 weeks before surgery.
Serum estradiol concentrations were measured by solid-phase extraction followed by liquid chromatography–tandem mass spectrometry detection. Toxic effects were evaluated using the National Cancer Institute terminology criteria, and Ki-67 was assessed by immunohistochemistry.
A total of 180 women were randomized into 1 of the 3 arms; median (IQR) age was 66 (60-71) years, 63 (60-69) years, and 65 (61-70) years in the once-daily, 3-times-weekly, and once-weekly arms, respectively. In the intention-to-treat population (n = 171), the least square mean percentage change of serum estradiol was −89%, −85%, and −60% for exemestane once daily (n = 55), 3 times weekly (n = 56), and once weekly (n = 60), respectively. The difference in estradiol percentage change between the once-daily and 3-times-weekly arms was −3.6% (P for noninferiority = .37), whereas in compliant participants (n = 153), it was 2.0% (97.5% lower confidence limit, −5.6%; P for noninferiority = .02). Among secondary end points, Ki-67 and progesterone receptor were reduced in all arms, with median absolute percentage changes of −7.5%, −5.0%, and −4.0% for Ki-67 in the once-daily, 3-times-weekly, and once-weekly arms, respectively (once daily vs 3 times weekly, P = .31; once daily vs once weekly, P = .06), and −17.0%, −9.0%, and −7.0% for progesterone receptor, respectively. Sex hormone–binding globulin and high-density lipoprotein cholesterol had a better profile among participants in the 3-times-weekly arm compared with once-daily arm. Adverse events were similar in all arms.
In this randomized clinical trial, exemestane, 25 mg, given 3 times weekly in compliant patients was noninferior to the once-daily dosage in decreasing serum estradiol. This new schedule should be further studied in prevention studies and in women who do not tolerate the daily dose in the adjuvant setting.
Yet another combination to consider after CDK4/6i + ET in HR+ MBC!
The INSEMA trial showed that for early stage, T1-T2 clinically node negative breast cancer, sentinel lymph node biopsies should not be mandatory, and best clinical judgement can be used.
Imlunestrant (novel oral SERD) was active in patients with an ESR1 mutations, but otherwise did not offer a benefit in this population of women with ER+ HER2-neg MBC. Overall survival (OS) data is pending with further follow up.
Another trial with neoadjuvant immunotherapy showing improved results over chemotherapy alone. (12% higher PCR 48% vs 36%).
Dato-DXd is now approved in HR+, HER2-neg, metastatic breast cancer after prior therapy with endocrine-based therapy and chemotherapy. There was an impressive reduction in the risk of death or progression with an HR of 0.63. Watch out for ocular and pulmonary toxicity. HER2-ultra low testing will be burdensome but must be done for drug approval.
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