Ruth M. O’Regan, MD, professor, chair, Charles Ayrault Dewey Professorship of Medicine, Department of Medicine, the University of Rochester, physician-in-chief, Strong Memorial Hospital, associate director, Education and Mentoring, the Wilmot Cancer Institute at University of Rochester, discusses the development of oral selective estrogen receptor degraders (SERDs) in hormone receptor (HR)–positive breast cancer.

The randomized phase 3 EMERALD trial (NCT03778931) evaluated the oral SERD elacestrant vs standard endocrine therapy in pretreated patients with advanced or metastatic estrogen receptor–positive, HER2-negative breast cancer. Data from the study showed an advantage for the oral SERD over standard therapy, O’Regan says. Although it was a modest difference, elacestrant appeared to have efficacy in HR-positive breast cancer harboring 

The development of elacestrant and other oral SERDs could provide a treatment advantage over the SERD fulvestrant, which is administered through intramuscular injection, O’Regan notes. Additionally, oral SERDs won't have the same bioavailability issues as fulvestrant, and evaluating these agents further will be crucial, O’Regan explains. Adjuvant studies are being planned with oral SERDs, though there have not been much compelling data in the metastatic setting, and there are adverse effects, such as gastrointestinal toxicity, that need to be considered. O’Regan adds. 

Ultimately, oral SERDs would represent a more convenient treatment option for patients, O’Regan continues. In the early phase setting, encouraging data have been observed for the combination of oral SERDs with CDK4/6 inhibitors, and these regimens could be further explored in the future, O’Regan concludes.

Videos

Ruth M. O’Regan, MD, discusses the development of oral selective estrogen receptor degraders in hormone receptor–positive breast cancer.


Dr. O’Regan on the Development of Oral SERDs in Breast Cancer

Ruth O’Regan, MD; Joyce A. O’Shaughnessy, MD; Hope S. Rugo, MD, FASCO; and Debu Tripathy, MD, provide insight regarding recent updates from key clinical trials on the management of metastatic 

Data from the following clinical trials are discussed:

Latest findings from the phase 2 SUMMIT basket trial on neratinib plus trastuzumab plus fulvestrant for HR-positive MBC with activating 

 mutations (Jhaveri K, et al. 2020 SABCS. Poster PD1-05).

-positive metastatic breast cancer patients with central nervous system disease at baseline: Findings from the phase 3 NALA trial (Saura C, et al. 2020 SABCS. Poster PD13-09).

Neratinib + capecitabine sustains health-related quality of life (HRQoL) while improving progression-free survival (PFS) in patients with 

+ metastatic breast cancer and ≥2 prior HER2-directed regimens (Moy B, et al. 2020 SABCS. Poster PS9-02).

Final analysis of PERTAIN: A randomized, 2-arm, open-label, multicenter phase 2 trial assessing the efficacy and safety of first-line pertuzumab given in combination with trastuzumab plus an aromatase inhibitor in patients with 

-positive and hormone receptor–positive metastatic or locally advanced breast cancer (Arpino G, et al. 2020 SABCS. Poster PD3-02).

A randomized, open-label, phase 3 trial of pertuzumab re-treatment in 

-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab, trastuzumab, and chemotherapy: The Japan Breast Cancer Research Group-M05 (PRECIOUS) study (Yamamoto Y, et al. 2020 SABCS. Poster PD3-11).

Updated results from DESTINY-Breast01, a phase 2 trial of trastuzumab deruxtecan (T-DXd ) in 

-positive metastatic breast cancer (Modi S, et al. 2020 SABCS. Poster PD3-06).

Trastuzumab deruxtecan (T-DXd; DS-8201) with nivolumab in patients with HER2-expressing, advanced breast cancer: A 2-part, phase 1b, multicenter, open-label study (Hamilton E, et al. 2020 SABCS. Poster PD3-07).

Tucatinib vs placebo in combination with trastuzumab and capecitabine for patients with locally advanced unresectable or 

-positive metastatic breast cancer (HER2CLIMB): Outcomes by hormone receptor status (Hamilton E, et al. 2020 SABCS. Poster PD3-08).

Impact of tucatinib on health-related quality of life in patients with HER2+ metastatic breast cancer with stable and active brain metastases (Wardley A, et al. 2020 SABCS. Poster PD13-04).

Updated Data for Metastatic HER2+ Breast Cancer

A review of data presented at the 2020 San Antonio Breast Cancer Symposium (SABCS) examining the development and validation of prognostic tools for early stage 

First results from a phase 3 randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1–3 positive nodes, hormone receptor–positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < 25: SWOG S1007 (RxPONDER) (Kalinsky K, et al. 2020 SABCS. Poster GS3-00).

Primary outcome results from the WSG-ADAPT HR+/HER2- trial: Endocrine therapy alone in patients with intermediate or high-risk luminal early breast cancer (0–3 lymph nodes), Recurrence Score <26 and Ki67 response after preoperative endocrine therapy (Harbeck N., et al. 2020 SABCS. Poster GS4-04).

Continued efficacy of neratinib in patients with 

-positive early stage breast cancer: Final overall survival analysis from the randomized phase 3 ExteNET trial (Holmes FA, et al. 2020 SABCS. Poster PD3-03).

Bringing diarrhea under CONTROL: Dose escalation reduces neratinib-associated diarrhea and improves tolerability in 

-positive early stage breast cancer (Ruiz-Borrego M, et al. 2020 SABCS. Poster PS13-20).

The DAPHNe trial: A feasibility study of chemotherapy de-escalation based on response to neoadjuvant paclitaxel-HP (THP) in 

-positive breast cancer (Waks AG, et al. 2020 SABCS. Poster PD3-05).

Prognostic role of distant disease-free interval from completion of adjuvant trastuzumab in 

-positive early breast cancer: Analysis from the ALTTO (BIG 2-06) trial (Lambertini M, et al. 2020 SABCS. Poster PD3-04).

Prognostic Tools for Early-Stage HER2+ Breast Cancer 

Breast cancer experts discuss the evolution of HER2-targeted treatments, including margetuximab, trastuzumab, tucatinib, and neratinib, along with unmet needs in patients with 

Ruth O'Regan, MD, University of Rochester Medical Center

Articles

Dr. O’Regan on the Development of Oral SERDs in Breast Cancer

Updated Data for Metastatic HER2+ Breast Cancer

Prognostic Tools for Early-Stage HER2+ Breast Cancer

Current Treatment Landscape for HER2+ Breast Cancer