MSCO | QNA

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Q1. The current standard of care for 1L HER2-positive metastatic breast cancer (mBC) is pertuzumab + trastuzumab + taxane (PHT). According to the CLEOPATRA study, what was the overall survival benefit reported in the final analysis vs trastuzumab + taxane (HT)?

A: 18.5 months in PHT arm vs 12.4 months in HT arm (HR 0.62) 0%

B: 29.9 months in PHT arm vs 25.9 months in HT arm (HR 0.75) 0%

C: 56.5 months in PHT arm vs 40.8 months in HT arm (HR 0.68) 0%

D: No overall survival benefits was reported 0%

With a median follow-up of 50 months, the median overall survival in CLEOPATRA study was 56.5 months (95% confidence interval [CI], 49.3 to not reached) in the group receiving the pertuzumab combination, as compared with 40.8 months (95% CI, 35.8 to 48.3) in the group receiving the placebo combination (hazard ratio favoring the pertuzumab group, 0.68; 95% CI, 0.56 to 0.84; P<0.001), a difference of 15.7 months.

Ref: 1) SM Swain, et al. Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer. N Engl J Med 2015; 372:724-734

Q2. According to international guidelines, what is the preferred treatment regimen for 2L+ HER2-positive mBC?

A: Lapatinib + capecitabine 0%

B: Trastuzumab emtansine (T-DM1) 0%

C: Trastuzumab + chemotherapy 0%

D: Tucatinib + trastuzumab + capecitabine 0%

E: Trastuzumab deruxtecan (T-Dxd) 0%

Current international guidelines including NCCN, AGO, ABC4, and ASCO recommend T-DM1 as standard of care for the treatment of 2L+ HER2-positive mBC

Ref: 1) NCCN Breast Cancer Guidelines v4.2020; 2) Thill M, et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Advanced and Metastatic Breast Cancer: Update 2018. Breast Care 2018;13:209-215; 3) Cardoso F, et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4). Ann Oncol. 2018 Aug 1;29(8):1634-1657; 4) Giordano SH, et al. Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: ASCO Clinical Practice Guideline Update. Journal of Clinical Oncology 36, no. 26 (September 10, 2018) 2736-2740.

Q3. The novel anti-HER2 tyrosine kinase inhibitor (TKI), tucatinib, was studied in the phase II trial HER2CLIMB, what was the inclusion criteria on prior treatment in HER2CLIMB?

A: Prior treatment with trastuzumab 0%

B: Prior treatment with trastuzumab and pertuzumab 0%

C: Prior treatment with trastuzumab, pertuzumab, and T-DM1 0%

D: No specific inclusion criteria on prior treatment 0%

The HER2CLIMB trial recruited HER2-positive mBC patients who had previously been treated with trastuzumab, pertuzumab, and trastuzumab emtansine.

*Tucatinib is not yet approved in Hong Kong and Macau for treatment in HER2-positive mBC.

Ref: 1) Murthy RK, et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med 2020; 382:597-609.

Q4. The novel anti-HER2 antibody-drug conjugate, trastuzumab deruxtecan (T-Dxd), was studied in the single arm phase II trial DESTINY-Breast01, what was the primary endpoint of DESTINY-Breast01?

A: Overall response rate (ORR) 0%

B: Progression-free survival (PFS) 0%

C: Overall survival (OS) 0%

D: Duration of response (DoR) 0%

The primary endpoint of DESTINY-Breast01 was the overall response (complete response plus partial response) to trastuzumab deruxtecan therapy in patients who had tumor progression during or after the administration of trastuzumab emtansine.

*Trastuzumab deruxtecan is not yet approved in Hong Kong and Macau for treatment in HER2-positive mBC.

Ref: 1) Modi S, et al.Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med 2020; 382:610-621

Q5. The U.S. Food and Drug Administration (FDA) granted accelerated approval to trastuzumab deruxtecan for the treatment of:

A: 1L HER2-positive mBC 0%

B: 2L+ HER2-positive mBC 0%

C: 3L+ HER2-positive mBC 0%

D: None of the above 0%

Based on the results of the DESTINY-Breast01, the FDA approved trastuzumab deruxtecan for “adult patients with unresectable or metastatic HER2-positive BC who received two or more prior anti–HER2-based regimens in the metastatic setting”.

The US prescribing information includes a Boxed Warning to advise health care professionals and patients about the risk of interstitial lung disease (a group of lung conditions that causes scarring of lung tissues) and embryo-fetal toxicity.

*Trastuzumab deruxtecan is not yet approved in Hong Kong and Macau for treatment in HER2-positive mBC.

Ref: 1) FDA Approves Trastuzumab Deruxtecan for HER2+ Breast Cancer. Press Release December 2019. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-option-patients-her2-positive-breast-cancer-who-have-progressed-available. Accessed Dec 2020; 2) Trastuzumab deruxtecan. US Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761139s000lbl.pdf. Accessed Dec 2020.