Abstract 76P
Background
Previous studies in multiple metastatic tumors treated with diverse anticancer agents including immunotherapy, chemotherapy, mAb and TKIs have suggested the rate of tumor growth (g score) is inversely associated with survival (Gong et al 2020). We performed a retrospective analysis of patients (pts) with metastatic breast cancer (mBC) treated with trastuzumab deruxtecan (T-DXd), ado-trastuzumab emtansine (T-DM1), or chemotherapy to investigate their impact on g score and explore its association with clinical outcomes. This is the first report assessing g score in tumors treated with an ADC.
Methods
We investigated the association of g score and its derived tumor doubling time (TDT) in days with progression-free (PFS) and overall survival (OS) in two phase 3 studies in pts with HER2+ mBC (DESTINY-Breast03 (DB03), n = 524) and HER2-low mBC (DESTINY-Breast04 (DB04), n = 557). After grouping pts according to quartiles of gscores, we explored the association between g score and PFS/OS using Kaplan-Meier plots and Cox regression.
Results
Median g score (TDT in days) in DB03 was 0.0020/d (347d) and 0.0008/d (866d) (p<0.0001) with 20% and 41% of tumors demonstrating only regression without growth in the T-DM1 and T-DXd arms, respectively. In DB04, median g score was 0.0026/d (266d) and 0.0011/d (630d) (p<0.0001); with 15% and 29% of tumors demonstrating only regression in patients treated with physician’s choice of chemotherapy and T-DXd, respectively. Table: 76P
| DB03 | N | PFS | OS | ||
| Median (mo) | Hazard ratio | OS @ 1yr | Hazard ratio | ||
| dx | 159 | NR | 1.3 (0.7-2.3) | 96.8% | 7.6 (1-57.7) |
| Q1 | 68 | NR | 1 | 100% | 1 |
| Q2 | 68 | 16.8 | 2.5 (1.4-4.6) | 98.5% | 5.3 (0.6-47.5) |
| Q3 | 68 | 7 | 14 (7.7-25.6) | 92.4% | 18.1 (2.3-139.4) |
| Q4 | 67 | 2.8 | 68.2 (35.6-130.7) | 68.3% | 55.7 (7.6-409.3) |
| DB04 | |||||
| dx | 136 | 15.2 | 1.3 (0.9-2) | 82.1% | 3.9 (2-7.8) |
| Q1 | 79 | 18.8 | 1 | 100% | 1 |
| Q2 | 78 | 10 | 2.6 (1.7-4) | 86.9% | 3.3 (1.6-7) |
| Q3 | 78 | 6.9 | 7.9 (5.2-12) | 71.9% | 6.7 (3.4-13.5) |
| Q4 | 78 | 2.4 | 47.8 (29.3-78) | 52.2% | 11.3 (5.7-22.2) |
NR: not reached. Q, quartile of g score; dx: tumors with only regression and no growth
Conclusions
Compared to control therapies, T-DXd significantly reduced the rate of tumor growth. In both studies, g scores were inversely associated with PFS and OS. Prospective studies should evaluate g score’sassociation with OS and assess its potential use as an early response endpoint to accelerate drug development and reduce a patient’s exposure to agents with limited activity.
Clinical trial identification
NCT03529110, NCT03734029.
Editorial acknowledgement
Legal entity responsible for the study
Daiichi Sankyo and AstraZeneca.
Funding
Daiichi Sankyo and AstraZeneca.
Disclosure
P. He, D. Gambhire, H. Zhou, X. Ma, Y. Emura, A. Laadem, D. Leung, O. Rixe: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. All other authors have declared no conflicts of interest.