Laura Spring, MD, attending physician, Medical Oncology, Massachusetts General Hospital, instructor of medicine, Harvard Medical School, discusses next steps of the phase 1/2 AMEERA-1 trial (NCT03284957) in estrogen receptor (ER)–positive, HER2-negative advanced breast cancer.

The AMEERA-1 trial is evaluating the novel, oral selective ER degrader (SERD) amcenestrant as a single agent and in combination with other anti-cancer therapies, such as the CDK4/6 inhibitor palbociclib (Ibrance) in postmenopausal women with ER-positive/HER2-negative advanced breast cancer, Spring says. Updated results from the study demonstrated encouraging efficacy with the combination regimen in this patient population.

Looking to the future, further enrollment and follow-up data of the AMEERA-1 trial and other studies evaluating combinations with oral SERDs are needed, Spring says. Although options with oral SERDs will be valuable additions to the ER-positive, HER2-negative paradigm, it is unknown where these agents will fit in. However, these agents appear to yield increased efficacy in patients who harbor 

Additionally, it is necessary to evaluate whether these agents have utility in the adjuvant setting to reduce the onset of endocrine resistance and recurrences, Spring concludes.

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Laura Spring, MD, discusses next steps of the phase 1/2 AMEERA-1 trial in estrogen receptor–positive, HER2-negative advanced breast cancer.  



Dr. Spring on Next Steps of the AMEERA-1 Trial in ER+/HER2- Advanced Breast Cancer 

Laura Spring, MD, attending physician, Medical Oncology, Massachusetts General Hospital, instructor of medicine, Harvard Medical School, discusses the rationale for the ongoing phase 1/2 AMEERA-1 trial (NCT03284957) in estrogen receptor (ER)–positive, HER2-negative advanced breast cancer.

The AMEERA-1 trial is evaluating the novel, oral selective ER degrader (SERD) amcenestrant as a single agent and in combination with other anti-cancer therapies, such as the CDK4/6 inhibitor palbociclib (Ibrance) in postmenopausal women with ER-positive/HER2-negative advanced breast cancer, Spring says. The development of oral SERDs has been an area of research in this patient population and evaluating combination regimens with these agents is a logical next step to build upon single-agent activity. 

During the 2021 San Antonio Breast Cancer Symposium, updated findings from AMEERA-1 were presented in a virtual poster. The results showed that giving 200 mg of amcenestrant in combination with the approved dose of palbociclib demonstrated a median progression-free survival of 14.7 months at a median follow-up of 14.8 months. The overall response rate with the combination was 32.4% and the clinical benefit rate was 73.5%.

Safety findings were consistent with previous results, suggesting that amcenestrant is well tolerated in this patient population and should be further evaluated in combination regimens, Spring concludes.

Laura Spring, MD, discusses the rationale for the ongoing phase 1/2 AMEERA-1 trial in estrogen receptor–positive, HER2-negative advanced breast cancer.  



Dr. Spring on the Rationale for the AMEERA-1 Trial in ER+/HER2- Advanced Breast Cancer 

Experts in breast cancer discuss precision medicine in treatment of patients with metastatic triple negative breast cancer.

Data from the following clinical trials are discussed:

KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. (Cortes J et al. 2020 ASCO annual meeting. Abstract 1000.)

TBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response pathway genes (Olaparib Expanded). (Tung NM et al. 2020 ASCO annual meeting. Abstract 1002.)

Results of a phase II randomized trial of cisplatin +/- veliparib in metastatic triple-negative breast cancer and/or germline 

-associated breast cancer (SWOG S1416). (Sharma P et al. 2020 ASCO annual meeting. Abstract 1001.)

Veliparib plus carboplatin-paclitaxel in patients with HER2-negative advanced/metastatic gBRCA-associated breast cancer: Results in hormone receptor-positive and triple-negative breast cancer subgroups from the phase III BROCADE3 trial. (Ayoub J et al. 2020 ESMO Breast Cancer annual meeting. Abstract 140O.)

Final results of the double-blind placebo-controlled randomized phase II LOTUS trial of first-line ipatasertib + paclitaxel for inoperable locally advanced/metastatic triple-negative breast cancer. (Dent R et al. 2020 ESMO Breast Cancer annual meeting. Abstract 139O.)

Precision Medicine in Metastatic Triple Negative Breast Cancer

KOLs in breast cancer provide insights on de-escalation of adjuvant anti-HER2 therapy and need for HER2 testing of residual disease after neoadjuvant therapy.

Three-year follow-up of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2-blockade for HER2-positive breast cancer (TRAIN-2): A randomized phase III trial. (van der Voort A et al. 2020 ASCO annual meeting. Abstract 501.)

Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer. (Harbeck N et al. 2020 ASCO annual meeting. Abstract 500.)

Adjuvant trastuzumab emtansine (T-DM1) vs trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2+ breast cancer: Subgroup analysis from KATHERINE. (Loibl S et al. 2020 ESMO Breast Cancer annual meeting. Abstract 96O.)

HER2+ Early-Stage Breast Cancer: Peri-Operative Therapy

Breast cancer experts review recently approved treatment options for relapsed or refractory HER2+ MBC, their intracranial efficacy, and sequencing of therapies.

Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer: HER2CLIMB. (Murthy RK et al. 

Trastuzumab deruxtecan in previously treated HER2-positive breast cancer: DESTINY-Breast01. (Modi S et al. 

Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2+ metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: phase III NALA trial. (Saura C et al. 

Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases: HER2CLIMB. (Lin NU et al. 2020 ASCO annual meeting. Abstract 1005.)

CNS metastases in HER2-positive metastatic breast cancer treated with trastuzumab deruxtecan: DESTINY-Breast01 subgroup analyses. (Jerusalem G et al. 2020 ESMO Breast Cancer annual meeting. Abstract 138O.)

Impact of neratinib on development and progression of central nervous system metastases in patients with HER2-positive metastatic breast cancer: Findings from the NALA, NEfERT-T, and TBCRC 022 trials. (Awada A et al. 2019 SABCS. Poster P2-20-01.)

Trastuzumab deruxtecan vs investigator's choice for HER2-low breast cancer that has spread or cannot be surgically removed: DESTINY-Breast04. (NCT03734029. Updated October 6, 2020. https://clinicaltrials.gov/ct2/show/NCT03734029)

Metastatic HER2+ Breast Cancer

Sarah Sammons, MD, and Julie Collins, MD, discuss the study details of the PARSIFAL and BYLieve trials in patients with metastatic HR+ breast cancer.

PARSIFAL: A randomized, multicenter, open-label, phase II trial to evaluate palbociclib in combination with fulvestrant or letrozole in endocrine-sensitive patients with ER[+]/HER2[-] metastatic breast cancer. (Llombart-Cussac A et al. 2020 ASCO annual meeting. Abstract 1007.)

Alpelisib + fulvestrant in patients with 

-mutated HR+/HER2- advanced breast cancer previously treated with CDK4/6 inhibitor + aromatase inhibitor: BYLieve study results. (Rugo HS et al. 2020 ASCO annual meeting. Abstract 1006.)

Metastatic HR+ Breast Cancer

Laura Spring, MD, medical oncologist at Massachusetts General Hospital Cancer Center and instructor in medicine at Harvard Medical School, discusses the association between pathologic complete response (pCR) and neoadjuvant chemotherapy in patients with breast cancer at the 2018 San Antonio Breast Cancer Symposium.

Spring and her colleagues performed the largest meta-analysis to date looking at the prognostic significance of achievement of pCR following neoadjuvant chemotherapy in all breast cancer subtypes. Investigators focused on studies that reported pCR rates as well as long-term outcomes based on pCR or residual disease.

Any study that used neoadjuvant chemotherapy and reported both pCR rates and long-term outcomes were included; however, these studies had to have enrolled at least 25 patients or more, and the stricter definition of pCR endorsed by the FDA was used. Studies were excluded from the analysis if participants received prior radiation or endocrine therapy, while others were included irrespective of whether patients had received anti-HER2 therapy or not. Investigators found that achieving a pCR following neoadjuvant chemotherapy had a significant association with decreased recurrence and improved overall survival, says Spring.

Laura Spring, MD, Massachusetts General Hospital

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