T-DXd Improves Survival in HER2-Positive BC Versus Capecitabine-Based Regimens

Ian Krop, MD, PhD

Results from the phase 3 DESTINY-Breast02 trial (NCT03523585) showed that trastuzumab deruxtecan (T-DXd) led to a 34% reduction in death and a 13-month increase in overall survival (OS) for patients with advanced HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine (T-DM1; Kadcyla) compared with treatment of physician’s choice (TPC).¹

These results, which were presented at the 2022 San Antonio Breast Cancer Symposium (SABCS), are consistent with findings from the 2019 phase 2 DESTINY-Breast01 trial (NCT03248492), which demonstrated T-DXd as a viable treatment for patients with HER2-positive breast cancer and led to the accelerated approval of T-DXd for patients with metastatic or unresectable breast cancer.

“(The findings from) the phase 3 DESTINY-Breast02 trial demonstrated a statistically significant and clinically meaningful improvement in both progression-free and overall survival compared to treatment of physicians choice in the post-T-DM1 setting,” study author Ian Krop, MD, PhD, a chief clinical research officer at the Yale Cancer Center, said in a presentation of this data. “DESTINY-Breast02 confirms the favorable benefit-risk ratio of T-DXd in patients with advanced HER2-positive breast cancer.”

In the trial, 608 patients with metastatic breast cancer who had previously received 2 lines of T-DM1 treatment were randomized to receive either T-DXd (n = 406) or a physician-recommended combination of capecitabine with either trastuzumab (Herceptin) or lapatinib (Tykerb; n= 202).

The patients who received T-Dxd had a median age of 54.2 years and a median treatment time of 11.3 months. The patients who received TPC had a median age of 54.2 years and a median treatment time of approximately 4.5 months.

The objective response rate for the T-DXd arm was 69.7%, compared to 29.2% in the TPC arm.

Krop also explained that the median progression-free survival (PFS) was 17.8 months for patients with T-DXd while it was 6.9 months for patients with TPC (HR, 0.3589), demonstrating a 64% reduction in the risk of disease progression or death.

Krop also shared that 42% of patients who received T-DXd were progression-free after two years, compared to 13.9% for the patients who received TPC.

After one year, 89.4% of patients who received T-DXd were alive, compared with 74.7% of patients who received TPC.

Regarding OS, median OS was 39 months and 26.5 months in the T-DXd and TPC arms, respectively (HR,0.66), indicating a 34% reduction in the risk of death with T-DXd compared to TPC.

Krop also shared that the percentage of patients who had to discontinue therapy because of an adverse reaction to the drug was 14% with T-Dxd versus 5% with TPC. He noted that most of these patients had to discontinue due to interstitial lung disease or pneumonitis.

Krop emphasized that even though this trial studied T-DXd as the third line of therapy, these results should not be used to change any current practices of using T-DXd as a second-line of therapy because oncologists “generally don’t hold back” the superior therapy for patients with cancer.

“T-DXd should still be used in the second line setting in virtually all patients (with advanced HER2-positive breast cancer),” he concluded.

_REFERENCE:

_{Krop, Ian et al T-DXd yields superior outcomes over chemotherapy-based regimens in patients previously treated with T-DM1 participating in the phase III DESTINY-Breast02 trial. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. Abstract GS2-01.}