Endocrine Therapy May Benefit Women in Postmenopause as Much as Chemoendocrine

21-gene profiling is also preferred for patients with 1 to 3 pathologically positive lymph nodes, according to a presentation at the Hematology/Oncology Pharmacy Association conference.

Postmenopausal women with 1 to 3 pathologically positive lymph nodes and individuals who are postmenopausal could benefit just as much from endocrine therapy as chemoendocrine therapy and with less risk of a bone fracture, according to a presentation at the Hematology/Oncology Pharmacy Association Annual Conference 2022 in Boston, Massachusetts.

Additionally, 21-gene profiling is also preferred for postmenopausal women with 1 to 3 pathologically positive lymph nodes.

Jeremy Pappacena, PharmD, BCOP, a clinical pharmacy specialist of hematology and oncology at Allegheny Health Network, discussed the updates regarding these treatments, focusing on 3 different trials: MonachE, RxPonder, and SALSA.

“Over the years, we have seen several gene expression assays developed to help guide therapy for patients with HR+ breast cancer,” she said during the session.

The 4 most common are Oncotype Dx, MammaPrint, Prosigna, and EndoPredict.

“Notably, Oncotype Dx in the lymph node negative setting was the only one that developed a prognostic and predictive value and led to its [National Comprehensive Cancer Network] preferred status,” Pappacena said. “We were able to identify, based on recurrence scores and patients’ menopausal status, whether they would derive any benefit from adjuvant chemotherapy followed by endocrine therapy or if they could proceed to adjuvant endocrine therapy alone.”

The Rx Ponder multicenter, open-label, prospective, randomized trial included individuals aged 18 years or older’ had HR+, HER2- early-stage breast cancer that was pathologic Nodal Stage 1, which is 1 to 3 positive regional lymph nodes; underwent primary surgery with sentinel LN biopsy or axillary LN dissection; and were eligible for chemotherapy with anthracycline and/or taxine.

Individuals underwent either chemoendocrine therapy or endocrine-only therapy.

The primary endpoints were the invasive disease-free survival (IDFS) and chemotherapy benefits based on recurrence score (RS). The secondary endpoints were distant relapse free survival (DRFS) and overall survival (OS).

Overall, there were no differences seen in the 5-year DRFS or in the 5-year IDFS for either treatment option, with chemoendocrine at a rate of 94.9% and 92.2%, respectively, and endocrine-only therapy at rates of 93.9% and 91%, respectively.

There was no difference for women who were postmenopausal, with the 5-year IDFS at a 91.9% rate for endocrine-only therapy and 91.3% for chemoendocrine therapy. Additionally, the 5-year DRFS was 94.4% for both groups.

However, there were some significant differences in treatment for women who were postmenopausal. For the 5-year IDFS, individuals in the chemoendocrine group benefited more at a rate of 93.9% compared with 89% in the endocrine-only group. Additionally for the 5-year DRFS, individuals in the chemoendocrine group benefited at a rate of 96.1% compared with 92.8% in the endocrine-only therapy group.

All patients younger than aged 50 years, regardless of tumor and size, seemed to be the most affected.

With an RS of 16 to 20, individuals in the chemoendocrine group benefited at a rate of 91.5% compared with 83.8% in the endocrine group, while those with a score of 21 to 15 benefited at rates of 92.4% and 85.2% respectively.

Because of these new results, the SALSA trial was designed to further examine individuals who received 5 year of adjuvant endocrine therapy.

SALSA was a multicenter, open-label, phase 3, randomized, trial and included women who had early-stage HR+ invasive breast cancer, received 5 years of the adjuvant endocrine therapy, were younger than aged 80 years, and were postmenopausal.

Individuals either received anastrozole 1 mg daily orally for 2 or for 5 years.

The primary endpoint was disease-free survival, while the secondary endpoints were OS and time-to-event analyses for contralateral breast cancer, first clinical facture, or second primary cancer.

There were no differences in the risk of contralateral or second primary cancer or survival outcomes.

However, there was an increased risk of bone fracture at 6.3% in the 5-year arm compared with 4.7% in the 2-year arm.

Finally, the MonarchE trial was conducted to further examine endocrine therapy with an adjunct.

The MonarchE trial was a multicenter, open-label, phase 3, prospective, randomized trial that included adults with early-stage HR+, HER2-, high-risk breast cancer, who received radiotherapy and surgery and/or neo-adjuvant chemotherapy as indicated.

Individuals received either a standard endocrine therapy for 5 to 10 years or received the standard endocrine therapy for 5 to 10 years, plus abemaciclib 150 mg orally, twice a day for 2 years.

The primary endpoint was IDFS, while the secondary endpoints were DRFS, OS, and safety.

The results showed that the 2-year IDFS for endocrine therapy with abemaciclib was 92.2% compared with 88.7% with the endocrine-only therapy, and the 2-year DRFS was 93.6% compared with 90.3%, respectively.

There were no significant new adverse events (AEs), but abemaciclib dose adjustments did occur in 68.1% of individuals and 16.6% of individuals discontinued treatment because of AEs. The most common AE was diarrhea.

Abemaciclib is FDA-approved in combination with endocrine therapy for adjuvant treatment of individuals with HR+, HER2-, node-positive, early breast cancer at high risk of recurrence and a Ki-67 of greater than or equal to 20%.

Reference

Pappacena J. Updates for management of early-stage breast cancer: old dogs, new tricks. Hematology/Oncology Pharmacy Association Annual Conference 2022. March 30, 2022; Boston, MA.