Sara A. Hurvitz, MD, on Updated Survival Results on T-DXd vs T-DM1 in Metastatic Breast Cancer
2022 San Antonio Breast Cancer Symposium
Sara A. Hurvitz, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, discusses phase III findings from the DESTINY-Breast03 study, which showed that second-line treatment with fam-trastuzumab deruxtecan-nxki (T-DXd) led to longer overall survival compared with ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer. Patients treated with T-DXd had a 36% lower risk of death than those treated with T-DM1 (Abstract GS2-02).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
DESTINY-Breast 03 was a phase 3 randomized clinical trial looking at T-DXd versus T-DM1 in patients with HER2-positive metastatic breast cancer that had progressed after trastuzumab and a taxane.
The primary endpoint was median progression-free survival by blinded independent central review. And a key secondary endpoint was overall survival. The data were originally presented in September 2021 when we showed a stunning significant improvement in median PFS associated with T-DXd, and that was really immediately practiced changing.
But the overall survival data were not mature at that time. So at San Antonio we provided updated overall survival results. We had seen 169 overall survival events in July 2022, which triggered the analysis. We showed that the median overall survival had not been reached yet for either treatment arm. However, there was a statistically significant improvement in overall survival seen with T-DXd.
The hazard ratio was 0.64. In addition, we presented updated median progression-free survival by independent review. And now the median PFS had been met with T-DXd and was 28.8 months, which was roughly four times longer than seen with T-DM1.
In addition, we saw an objective response rate of almost 80% with T-DXd, which was higher than with T-DM1. 21% of patients having a complete response compared to 9.5% with T-DM1. So overall the results show real benefits with T-DXd firmly placing this as the standard of care in regions where it's available after trastuzumab and taxane.
In terms of safety, the safety data looked fairly similar to what was previously reported. However, there were more all grade ILD events noted this time with longer treatment duration and longer follow-up. 15% or so of patients treated with T-DXd had ILD compared to about 10% at the time of initial reporting. But all of these additional events were grade one or two. There were no new grade three events and zero grade four or five events.
So in summary, I think these data really solidly place T-DXd as the standard of care in the second line setting after trastuzumab and taxane. We have exciting studies ongoing looking at T-DXd in the frontline setting, in the adjuvant setting, so I'm looking forward to seeing more data emerge relating to this very effective regimen.
The ASCO Post Staff
Marleen Kok, MD, PhD, of the Netherlands Cancer Institute, discusses the most important advances in early breast cancer treatment during the past year for patients with triple-negative, HER2-positive, and estrogen receptor–positive disease. Dr. Kok also addresses long-term treatment toxicities and quality of life.
The ASCO Post Staff
Judy C. Boughey, MD, of Mayo Clinic, talks about why breast-conserving therapy may be a treatment option for some patients with multiple breast lesions. For most patients who present with two or three sites of cancer in one breast, mastectomy is recommended. But results from the ACOSOG Z11102 (Alliance) suggest that for women with multiple ipsilateral breast cancer, breast-conserving surgery with adjuvant radiation therapy and lumpectomy site boosts may be beneficial (Abstract GS4-01).
The ASCO Post Staff
François-Clément Bidard, MD, PhD, of the Institut Curie, discusses overall survival results from the STIC CTC trial. To guide the choice between chemotherapy and endocrine therapy for patients with metastatic, estrogen receptor–positive/HER2-negative breast cancer, researchers compared circulating tumor cell (CTC) count to physician’s choice of treatment. The data suggest that the CTC count resulted in better long-term outcomes (Abstract GS3-09).
The ASCO Post Staff
Nicholas C. Turner, MD, PhD, of London’s Institute of Cancer Research and The Royal Marsden, discusses phase III results from the CAPItello-291 clinical trial, which showed that in patients with hormone receptor–positive, HER2-negative tumors resistant to aromatase inhibitors, adding the investigational AKT inhibitor capivasertib to fulvestrant doubled the median progression-free survival compared with placebo plus fulvestrant (Abstract GS3-04).
The ASCO Post Staff
Yara Abdou, MD, of the University of North Carolina, discusses results from the RxPONDER SWOG S1007 study, which showed that non-Hispanic Black women with hormone receptor–positive/HER2-negative breast cancer with one to three involved lymph nodes and a recurrence score of ≤ 25 have worse outcomes than non-Hispanic White women. In addition, Black patients were more likely to accept treatment assignment than their White counterparts and were just as likely to remain on estrogen therapy at 6 and 12 months, suggesting that outcome differences may be less likely attributable to lack of treatment compliance within the first year (Abstract GS1-01 ).