Metastatic HER2-Low Breast Cancer

The DESTINY-Breast04 trial (NCT03734029) randomly assigned 557 women in a 2:1 ratio to receive either trastuzumab deruxtecan or the physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel). Patients had received one or two prior lines of chemotherapy. The primary end point was PFS in the hormone receptor–positive group (88.7% of patients). The secondary end points were PFS in the total population, OS in the total population, and OS in the hormone receptor–positive group.[54][Level of evidence A1]

The DESTINY-Breast04 trial (NCT03734029) randomly assigned 557 women in a 2:1 ratio to receive either trastuzumab deruxtecan or the physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel). Patients had received one or two prior lines of chemotherapy. The primary end point was PFS in the hormone receptor–positive group (88.7% of patients). The secondary end points were PFS in the total population, OS in the total population, and OS in the hormone receptor–positive group.[54][Level of evidence A1]

In the hormone receptor–positive cohort, the median PFS was 10.1 months for patients who received trastuzumab deruxtecan and 5.4 months for patients who received the physician’s choice of chemotherapy (HRdisease progression or death, 0.51; P < .001). The OS was 23.9 months for patients who received trastuzumab deruxtecan and 17.5 months for patients who received the physician's choice of chemotherapy (HRdeath, 0.64; P = .003).

The DESTINY-Breast04 trial (NCT03734029) randomly assigned 557 women in a 2:1 ratio to receive either trastuzumab deruxtecan or the physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel). Patients had received one or two prior lines of chemotherapy. The primary end point was PFS in the hormone receptor–positive group (88.7% of patients). The secondary end points were PFS in the total population, OS in the total population, and OS in the hormone receptor–positive group.[54][Level of evidence A1]

Among all patients, the median PFS was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (HRdisease progression or death, 0.50; P < .001). The OS was 23.4 months in the trastuzumab deruxtecan group and 16.8 months in the physician's choice group (HRdeath, 0.64; P = .001).

The DESTINY-Breast04 trial (NCT03734029) randomly assigned 557 women in a 2:1 ratio to receive either trastuzumab deruxtecan or the physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel). Patients had received one or two prior lines of chemotherapy. The primary end point was PFS in the hormone receptor–positive group (88.7% of patients). The secondary end points were PFS in the total population, OS in the total population, and OS in the hormone receptor–positive group.[54][Level of evidence A1]

Drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events.

The phase III, randomized, open-label DESTINY-Breast06 trial (NCT04494425) included patients with ER-positive metastatic breast cancer with low HER2 expression (with a score of 1+ or 2+ on IHC analysis and negative results on in situ hybridization) or ultralow HER2 expression (with a score of 0 on IHC analysis with membrane staining). These patients previously received one or more lines of endocrine-based therapy and no previous chemotherapy for metastatic breast cancer. The trial randomly assigned 866 patients in a 1:1 ratio to receive either trastuzumab deruxtecan or the physician’s choice of chemotherapy. A total of 713 patients had HER2-low disease and 153 patients had HER2-ultralow disease. The primary end point was PFS.[55]

The phase III, randomized, open-label DESTINY-Breast06 trial (NCT04494425) included patients with ER-positive metastatic breast cancer with low HER2 expression (with a score of 1+ or 2+ on IHC analysis and negative results on in situ hybridization) or ultralow HER2 expression (with a score of 0 on IHC analysis with membrane staining). These patients previously received one or more lines of endocrine-based therapy and no previous chemotherapy for metastatic breast cancer. The trial randomly assigned 866 patients in a 1:1 ratio to receive either trastuzumab deruxtecan or the physician’s choice of chemotherapy. A total of 713 patients had HER2-low disease and 153 patients had HER2-ultralow disease. The primary end point was PFS.[55]

In patients with HER2-low disease, the median PFS was 13.2 months (95% CI, 11.4–15.2) in the trastuzumab deruxtecan group and 8.1 months (95% CI, 7.0–9.0) in the chemotherapy group (HR, 0.62; 95% CI, 0.51–0.74; P < .001).[55][Level of evidence B1]

The phase III, randomized, open-label DESTINY-Breast06 trial (NCT04494425) included patients with ER-positive metastatic breast cancer with low HER2 expression (with a score of 1+ or 2+ on IHC analysis and negative results on in situ hybridization) or ultralow HER2 expression (with a score of 0 on IHC analysis with membrane staining). These patients previously received one or more lines of endocrine-based therapy and no previous chemotherapy for metastatic breast cancer. The trial randomly assigned 866 patients in a 1:1 ratio to receive either trastuzumab deruxtecan or the physician’s choice of chemotherapy. A total of 713 patients had HER2-low disease and 153 patients had HER2-ultralow disease. The primary end point was PFS.[55]

Grade 3 or higher adverse events occurred in 52.8% of patients in the trastuzumab deruxtecan group and 44.4% of patients in the chemotherapy group. Interstitial lung disease occurred in 49 patients (11.3%; three events had grade 5 severity) and pneumonitis occurred in one patient (0.2%; grade 2).