DESTINY-Breast01 Data

ENHERTU efficacy evaluated in DESTINY-Breast01

A single-arm trial of 184 females with HER2+ unresectable and/or mBC who had received ≥2 prior anti-HER2 therapies. Patients received ENHERTU 5.4 mg/kg IV once every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was confirmed ORR assessed by ICR using RECIST v1.1. Secondary endpoints included DOR and PFS.1,2

ENHERTU monotherapy delivered durability that resets expectations to patients who progressed on 2L anti-HER2 therapy1,2

ORR, mDOR and mPFS results with ENHERTU in DESTINY-Breast01 depicting a 60.3% confirmed ORR (n=111; 95% CI: 52.9, 67.4; 4.3% CR [n=8] + 56% PR [n=103]; N=184), 14.8 mDOR (n=111; 95% CI: 13.8, 16.9), and a 16.4-month mPFS (n=184; 95% CI: 12.7, NR).
ORR, mDOR and mPFS results with ENHERTU in DESTINY-Breast01 depicting a 60.3% confirmed ORR (n=111; 95% CI: 52.9, 67.4; 4.3% CR [n=8] + 56% PR [n=103]; N=184), 14.8 mDOR (n=111; 95% CI: 13.8, 16.9), and a 16.4-month mPFS (n=184; 95% CI: 12.7, NR).

ENHERTU received accelerated approval from FDA for its initial indication—based on tumor response and duration of response—for the treatment of patients with HER2+ unresectable and/or mBC who had received 2 prior anti-HER2 therapies. FDA has not reviewed these PFS data. DESTINY-Breast03 is a Phase 3 confirmatory trial that supported full approval of ENHERTU for 2L HER2+ mBC.3

aORR defined as CR+PR per RECIST v1.1 in the ITT population as evaluated by ICR.1,2

bMedian DOR based on Kaplan-Meier estimate. DOR based on a median duration of follow-up of 11.1 months.1

cNot an FDA-reviewed endpoint. Based upon median duration of follow-up of 11.1 months at data cutoff date of August 1, 2019.2

Safety data from Phase 2 DESTINY-Breast01 and Phase 1 DS8201-A-J101 established the initial benefit-risk profile for ENHERTU (5.4 mg/kg, N=234)1

The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2+ breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in Phase 2 DESTINY-Breast01 and Phase 1 Study DS8201-A-J1011

  • The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (79%), decreased white blood cell count (70%), decreased hemoglobin (70%), decreased neutrophil count (62%), fatigue (59%), vomiting (47%), alopecia (46%), increased aspartate aminotransferase (41%), increased alanine aminotransferase (38%), decreased platelet count (37%), constipation (35%), decreased appetite (32%), anemia (31%), diarrhea (29%), hypokalemia (26%), and cough (20%)1
  • Median duration of treatment was 7 months (range: 0.7-31)1
  • In the clinical trials, prophylactic or supportive treatment of ENHERTU-induced adverse events was not mandated and was per investigator’s discretion and institutional guidelines4

ILD and pneumonitis, including Grade 5 cases, have been reported with ENHERTU in DESTINY-Breast01 and DS-8201-A-J101; the majority were Grade 1 or 2 (n=16/22)1,4,d,e

  • In clinical studies, of the 234 patients with HER2+ unresectable or mBC treated with ENHERTU 5.4 mg/kg, ILD occurred in 9% of patients (n=22/234)1,4
    • Fatal outcomes due to ILD/pneumonitis occurred in 2.6% of patients (n=6/234)1
  • Median time to first onset was 4.1 months (range: 1.2-8.3)1

dILD includes events that were adjudicated as ILD: pneumonitis, interstitial lung disease, respiratory failure, organizing pneumonia, acute respiratory failure, lung infiltration, lymphangitis, alveolitis.1

eGrade 5=fatal cases.4

Ready to learn more about ENHERTU?
2L, second line; CI, confidence interval; CR, complete response; DOR, duration of response; FDA, Food and Drug Administration; HER2, human epidermal growth factor receptor 2; ICR, independent central review; ILD, interstitial lung disease; ITT, intent-to-treat; IV, intravenous; mBC, metastatic breast cancer; mDOR, median duration of response; mPFS, median progression-free survival; NR, not reached; ORR, objective response rate; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors.