Virginia G. Kaklamani, MD, professor of medicine, Division of Hematology/Oncology, University of Texas (UT) Health San Antonio, leader, Breast Cancer Program, UT Health San Antonio MD Anderson Cancer Center, discusses the evolution of oral selective estrogen receptor degraders (SERDs) in estrogen receptor (ER)–positive breast cancer.

The evolution of oral SERDs has led to excitement regarding the tolerability and safety profile of this class of agents, Kaklamani says. Additionally, oral SERDs have shown sensitivity in patients with 

 mutations, addressing an unmet need in this field, Kaklamani explains.

There is significant excitement regarding the potential approval of oral SERDs, as well as their investigation in combination with other agents, Kaklamani continues. Ongoing trials are currently looking at the benefit of combining oral SERDs with CDK4/6 inhibitors, what setting oral SERDs should be used in, and how this will shape the field of ER-positive breast cancer, Kaklamani concludes.

Funding supported by Stemline Therapeutics. Content independently developed by 

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Virginia G. Kaklamani, MD, discusses the evolution of oral selective estrogen receptor degraders in estrogen receptor-positive breast cancer.

Dr. Kaklamani on the Evolution of Oral SERDs in ER+ Breast Cancer

Virginia G. Kaklamani, MD, professor of medicine, Division of Hematology/Oncology, University of Texas (UT) Health San Antonio, leader, Breast Cancer Program, UT Health San Antonio MD Anderson Cancer Center,  discusses the use of adjuvant olaparib in germline

The phase 3 OlympiA trial (NCT02032823) is evaluating treatment with olaparib (Lynparza) in patients with germline 

 mutations and high-risk HER2-negative breast cancer.

The OlympiA trial demonstrated that patients with germline 

-mutant, high-risk breast cancer can benefit from receiving olaparib for one year in the adjuvant setting, Kaklamani says. This is the first adjuvant trial in breast cancer showing improved survival with a PARP inhibitor, Kaklamani explains.

Investigators are now examining whether the use of a PARP inhibitor can prevent cancers in those with a germline 

 mutation, Kaklamani continues. The results from OlympiA have also set the stage for further research examining whether it is beneficial to combine olaparib with a checkpoint inhibitor in this patient population, Kaklamani concludes.

Virginia G. Kaklamani, MD, discusses the use of adjuvant olaparib in germline BRCA1/2-mutant breast cancer.


Dr. Kaklamani on the Use of Adjuvant Olaparib in Germline BRCA1/2-Mutant Breast Cancer

Data from the following clinical trials are discussed:

+ breast cancer identifies recurrent pathway alterations associated with anti-HER2 resistance and new therapeutic vulnerabilities

GS1-05: Datopotamab deruxtecan (Dato-DXd) in advanced/metastatic HER2- breast cancer: results from the phase 1 TROPION-PanTumor01 study

GS04-09: Quality-of-life results from OlympiA: a phase 3, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after neoadjuvant chemotherapy in patients with germline 

After discussing a few more key datasets from the SABCS 2021 Virtual Meeting, expert panelists discuss how they would approach treatment in several subsets of breast cancer. 

SABCS 2021: Novel Approaches to Breast Cancer Management 

PD4-02: Safety and efficacy of a tucatinib-trastuzumab-capecitabine regimen for treatment of leptomeningeal metastasis in 

+ breast cancer: Results from TBCRC049, a phase 2 nonrandomized study

PD4-04: Updated results of tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated 

+ metastatic breast cancer with brain metastases (HER2CLIMB)

P1-18-26: Intracranial efficacy of tucatinib, palbociclib, and letrozole combination in patients with HR+/

P1-21-03: Efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of patients with 

+ breast cancer with or without brain metastases: a systematic review and meta-analysis

OT1-13-01: HER2CLIMB-04: phase 2 trial of tucatinib + trastuzumab deruxtecan in patients with 

+ locally advanced or metastatic breast cancer with and without brain metastases

Focusing on datasets from the SABCS 2021 Virtual Meeting, panelists consider novel approaches to the management of brain metastases in breast cancer.

SABCS 2021: Brain Metastases Updates in Breast Cancer 

GS3-01: Trastuzumab deruxtecan (T-DXd; DS-8201a) vs trastuzumab emtansine (T-DM1) in patients with 

–positive metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINYBreast03

GS3-02: Updated overall survival (OS) results from the phase 3 PHOEBE trial pyrotinib vs lapatinib in combination with capecitabine in patients with 

GS4-10: Neratinib + fulvestrant + trastuzumab for hormone receptor (HR)–positive, HER2-mutant metastatic breast cancer and neratinib + trastuzumab for triple-negative disease: latest updates from the SUMMIT trial

P2-13-10: First-in-human HER2-targeted bispecific antibody KN026 for the treatment of patients with 

+ metastatic breast cancer: results from a phase I study

P2-13-07: Zanidatamab (ZW25), a HER2-targeted bispecific antibody, in combination with chemotherapy for 

+ breast cancer: results from a phase 1 study

PD8-07: Evaluation of tucatinib + paclitaxel + pertuzumab + trastuzumab followed by AC (doxorubicin hydrochloride, cyclophosphamide) in high-risk HER2+ stage II/III breast cancer: results from the I-SPY2 trial

Expert panelists share their perspectives on metastatic breast cancer management datasets from the SABCS 2021 Virtual Meeting. 

SABCS 2021: Updates in Metastatic Breast Cancer

Virginia Kaklamani, MD, DSc, shares her excitement for an upcoming OncLive® "The TALK" program focusing on HER2-positive breast cancer updates from the SABCS 2021 Virtual Meeting. 

Coming Soon, HER2-Positive Breast Cancer: A Review of Data from the SABCS 2021 Virtual Meeting 

Virginia Kaklamani, MD, DSc, discusses data from the following presentation:

Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with 

+ metastatic breast cancer: results of the randomized, phase 3 study DESTINY-Breast03. (

T-DXd is a HER2-targeting antibody-drug conjugate approved for patients with advanced 

 (human epidermal growth factor receptor 2)–positive metastatic breast cancer (mBC) based on the results from DESTINY-Breast01 (NCT03248492). This is the first report of DESTINY-Breast03 (NCT03529110), a multicenter, open-label, randomized phase 3 study comparing the efficacy and safety of T-DXd vs T-DM1 in patients with 

+ mBC previously treated with trastuzumab and taxane. This is the first reported randomized study of T-DXd in breast cancer.

The primary end point was progression-free survival (PFS) by blinded independent central review (BICR).

Secondary end points include overall survival (OS), objective response rate (ORR), duration of response, PFS by investigator, and safety.

As of May 21, 2021, 524 patients were randomized. Median age was 54 years (range, 20-83).

Median treatment duration was 14.3 months (range, 0.7-29.8) with T-DXd vs 6.9 months (range, 0.7-25.1) with T-DM1.

The hazard ratio (HR) for PFS was 0.2840 (

 = 7.8 x 10-22); median PFS not reached for T-DXd vs 6.8 months for T-DM1.

The estimated 12-month OS event rates were 94.1% (95% CI, 90.3-96.4) for T-DXd and 85.9% (95% CI, 80.9-89.7) for T-DM1; HR: 0.5546 (95% CI, 0.3587-0.8576; 

 = .007172 did not cross prespecified boundary for significance).

Similar rates of treatment-emergent adverse events were observed. No drug-related deaths occurred in either arm. Adjudicated drug-related interstitial lung disease (ILD) occurred in 10.5% of patients with T-DXd (most [9.7%] grade 1/2; 0 grade 4/5) vs 1.9% with T-DM1 (all grade 1/2).

T-DXd demonstrated a highly statistically significant and clinically meaningful improvement in PFS vs T-DM1 in patients previously treated with trastuzumab and taxane for 

+ mBC. These data confirm that T-DXd (trastuzumab deruxtecan) is tolerable with manageable toxicity and a significant improvement in ILD profile vs studies performed in more heavily pretreated patients. This study will lead to a paradigm shift in the treatment of 

Virginia Kaklamani, MD, DSc, presents results of the DESTINY-Breast03 clinical trial of trastuzumab deruxtecan compared with trastuzumab emtansine as treatment for patients with HER2-positive metastatic breast cancer.

Virginia G. Kaklamani, MD, DSc

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