Trastuzumab Deruxtecan Improves Survival in HER-2 Positive Breast Cancer Compared to Capecitabine Regimens

Article

Patients with advanced HER2-positive breast cancer had improved progression-free and overall survival when treated with trastuzumab deruxtecan compared with capecitabin-based treatment, according to recent findings.

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 to treatment of physician’s choice (TPC), according to results found from the phase 3 DESTINY-Breast02 trial (NCT03523585).

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 54.7 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 39.2 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.

Related Videos
Barbara Smith, MD, PhD, spoke about the potential use of pegulicianine-guided breast cancer surgery based on reports from the phase 3 INSITE trial.
Patient-reported symptoms following surgery appear to improve with the use of perioperative telemonitoring, says Kelly M. Mahuron, MD.
Treatment options in the refractory setting must improve for patients with resected colorectal cancer peritoneal metastasis, says Muhammad Talha Waheed, MD.
Although immature, overall survival data from the KEYNOTE-868 trial may support the use of pembrolizumab plus chemotherapy in patients with endometrial cancer.
Dostarlimab plus chemotherapy appears to yield favorable overall survival in patients with mismatch repair proficient endometrial cancer.
Some patients with large B-cell lymphoma may have to travel a great distance for an initial evaluation for CAR T-cell therapy.
Brian Slomovitz, MD, MS, FACOG discusses the use of new antibody drug conjugates for treating patients with various gynecologic cancers.
Education is essential to referring oncologists manage toxicities associated with CAR T-cell therapy for patients with large B-cell lymphoma.
There is no absolute age cutoff where CAR T cells are contraindicated for those with large B-cell lymphoma, says David L. Porter, MD.
David L. Porter, MD, emphasizes referring patients with large B-cell lymphoma early for CAR T-cell therapy consultation.
Related Content