Table 1.
Key trials of T-DM1, T-DXd, SG, and EV that led to FDA approval.
| Trial | Drugs | Phase | No. of pts. | Population | Primary Endpoint | Grade ≥ 3 AEs |
|---|---|---|---|---|---|---|
| EMILIA (NCT008291666) | T-DM1 vs. lapatinib + capecitabine | III | 991 | HER2+ MBC previously treated with taxanes + T | mPFS: 9.6 vs. 6.4 m (p < 0.001) mOS: 30.9 vs. 25.1 m (p < 0.001) |
41% vs. 57% T-DM1: Thrombocytopenia (13%) Elevated ASAT (4%) Anemia (3%) |
| DESTINY-Breast02 (NCT03523585) [22] | T-DXd vs. T + capecitabine or lapatinib + capecitabine | III | 608 | HER2+ MBC previously treated with T-DM1 | mPFS: 17.8 vs. 6.9 m (p < 0.0001) | 53% vs. 44% ILD: 10% |
| DESTINY-Breast 03 (NCT03529110) [23] | T-DXd vs. T-DM1 | III | 524 | HER2+ MBC previously treated with T and taxane | mPFS: not reached vs. 6.8 m 12-mPFS rate (76 vs. 34%) (p < 0.0001) |
52% vs. 48% T-DXd: Neutropenia (19%) Thrombocytopenia (7%) ILD (1%) |
| DESTINY-Gastric01 (NCT03329690) [24] | T-DXd vs. physician of choice chemotherapy | II | 187 | HER2+ gastric cancer receiving at least 2 previous lines including T | ORR: 51% vs. 14% (p < 0.001) | Neutropenia (51%) Anemia (38%) Leucopenia (21%) ILD (2%) |
| DESTINY-Lung01 (NCT03505710) [25] | T-DXd | II | 91 | Metastatic HER2-mutant NSCLC refractory to standard treatment | ORR: 55% (mPFS: 8.2 m; mOS: 17.8 m) |
Neutropenia (19%) Anemia (10%) Nausea (9%) |
| ASCENT (NCT02574455) [26] | SG vs. single-agent CT | III | 468 | metastatic TNBC refractory to two prior lines | mPFS: 5.6 vs. 1.7 (p < 0.001) | Neutropenia (51%) Leukopenia (10%) Diarrhea (10%) Anemia (8%) |
| TROPiCS-02 (NCT03901339) [27] | SG vs. single-agent CT | III | 543 | HR+/HER2- mBC prior taxane, ET, CDK4/6 inhibitor and 2-4 prior CTs | mPFS: 5.5 vs. 4.0 m (p < 0.001) | Neutropenia (51%) Diarrhea (10%) |
| TROPHY-U-01 (NCT03547973) [28] | SG | II | 113 | mUC progressed after platinum-base CT and ICIs | ORR: 27% | Neutropenia (35%) Leukopenia (18%) Anemia (14%) Diarrhea (10%) Febrile neutropenia (10%) |
| EV-301 (NCT03474107) [29] | EV vs. docetaxel or paclitaxel of vinflunine | III | 608 | mUC progressed after platinum-base CT and ICIs | mOS: 12.9 vs. 9.0 m (p = 0.001) | Maculopapular rash (7%) Fatigue (6%) Neutropenia (5%) |
| EV-103 (NCT04223856) [30] | EV + pembro | Ib/II | 45 | mUC first-line cisplatin-ineligible pts | ORR 73% including 16% CR | Increased lipase (18%) Maculopapular rash (11%) Fatigue (11%) |
T-DM1: trastuzumab emtansine; MBC: metastatic breast cancer; mPFS: median progression-free survival; m: months; AEs: adverse events; mOS: median overall survival; ASAT: aspartate aminotransferase; T-DXd: trastuzumab deruxtecan; ILD: interstitial lung disease; T: trastuzumab; ORR: overall response rate; CR: complete remission; CT: chemotherapy; ICIs: immune checkpoint inhibitors; mUC: metastatic urothelial carcinoma; EV: enfortumab vedotin; SG: sacituzumab govitecan; HR: hormonal receptor; ET: endocrine therapy; TNBC: triple-negative breast cancer; NSCLC: non-small-cell lung cancer; pts: patients; nb: number.