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
Sean Khozin, MD, MPH, of the Massachusetts Institute of Technology, discusses the “external validity deficits” of randomized clinical trials, which still involve only about 5% of adults with cancer, who may differ in important ways from real-world populations. Dr. Khozin describes the reasons for low levels of participation and advocates for capturing the experience of patients not represented in traditional clinical trials, so real-world data can address these validity deficits.
The ASCO Post Staff
Erica L. Mayer, MD, PhD, of Dana-Farber Cancer Institute, discusses findings from the PACE study of patients with endocrine- and CDK4/6 inhibitor–pretreated estrogen receptor–positive/HER2-negative metastatic breast cancer who were randomly assigned to fulvestrant alone; fulvestrant and palbociclib; or fulvestrant, palbociclib, and avelumab. Combining palbociclib with fulvestrant beyond disease progression on a prior CDK4/6 inhibitor regimen did not improve progression-free survival compared with fulvestrant alone. A longer progression-free survival when a PD-L1 inhibitor was added to fulvestrant and palbociclib deserves further study. A baseline circulating tumor DNA analysis suggests that the potential benefit of palbociclib after progression on a prior CDK4/6 inhibitor may be influenced by ESR1 or PIK3CA status (Abstract GS3-06).
The ASCO Post Staff
Joseph A. Sparano, MD, of the Tisch Cancer Center at Mount Sinai Health System, discusses long-term clinical outcomes data that continue to show many women with early breast cancer can safely forgo chemotherapy, when guided by the 21-gene recurrence score result. The longer follow-up also showed that recurrences of breast cancer continue to occur years after the original diagnosis, although these recurrences were not prevented by chemotherapy use. Racial disparities were not explained by inequities in social determinants of health or treatment adherence, with Black women at higher risk of early recurrence within the first 5 years of diagnosis, but not later recurrence after 5 years (Abstract GS1-05).
The ASCO Post Staff
Per Karlsson, MD, PhD, of Sweden’s University of Gothenburg and the Sahlgrenska Comprehensive Cancer Center, discusses results from the POLAR study, which was a meta-analysis of three clinical trials of breast-conserving surgery with or without radiotherapy. POLAR is the first genomic classifier that appears not only to be prognostic for locoregional recurrence, but also predictive of radiotherapy benefit. Although patients with breast cancer who had a high POLAR score benefited from radiotherapy, patients with a low score did not, and may be candidates for omission of radiotherapy after breast-conserving surgery (Abstract GS4-03).
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 ).
