DESTINY-Breast04 Subgroup Analysis Confirms Trastuzumab Deruxtecan Benefit in HER2-low Metastatic Breast Cancer

Patient history and disease characteristics did not affect outcomes for patients with metastatic HER2-low breast cancer who received fam-trastuzumab deruxtecan-nxki in the DESTINY-Breast04 study.

breast cancer

Patient history and disease characteristics did not affect outcomes for patients with metastatic HER2-low breast cancer who received fam-trastuzumab deruxtecan-nxki (Enhertu) in the DESTINY-Breast04 study (NCT03734029), according to a subgroup analysis presented at the 2022 San Antonio Breast Cancer Symposium.1

Benefit was observed with trastuzumab deruxtecan across all prespecified subgroups included in the analysis for progression-free survival (PFS) and overall survival (OS). The included HER2 status by immunohistochemistry (IHC), prior lines of chemotherapy, prior CDK4/6 inhibitor treatment, age, and baseline central nervous system (CNS) metastases. PFS, objective response rate (ORR), and safety findings were included in the poster presentation.1

A total of 373 patients received trastuzumab deruxtecan 5.4 mg/kg every 3 weeks and 184 were treated with treatment of physician’s choice (TPC). Outcomes for the overall population of DESTINY-Breast04 have been previously reported.2

Among patients with hormone receptor–positive disease who received prior treatment with a CDK4/6 inhibitor the HR for disease progression was 0.55 (95% CI, 0.42-0.74) and 0.42 (95% CI, 0.28-0.64) for those who did not have prior CDK4/6 treatment. The median PFS for trastuzumab deruxtecan vs TPC in the CDK4/6 inhibitor group was 10.0 months vs 5.4 months and 11.7 months vs 5.9 months for those without prior CDK4/6 inhibition.1

Among those with low disease burden, the median PFS was 11.4 months with trastuzumab deruxtecan vs 5.1 months with TPC (HR, 0.41; 95% CI, 0.30-0.58). For those with high disease burden the median PFS was 9.5 months vs 4.8 months (HR, 0.58; 95% CI, 0.43-0.78).

Twenty-two patients had rapid progression defined as disease progression within 6 months of concluding prior chemotherapy in early breast cancer. The median PFS among patients who received trastuzumab deruxtecan (n = 14) was 8.2 months vs 2.2 months for those who received TPC (n = 8; HR, 0.38; 95% CI, 0.12-1.21). The benefit was also observed among those who did not have rapid progression with a 49% reduction in the risk of disease progression for those who received trastuzumab deruxtecan vs TPC (HR, 0.51; 95% CI, 0.41-0.64). The median PFS for these patients was 9.9 months vs 5.3 months, respectively.

Those with IHC 1+ disease who received trastuzumab deruxtecan had a median PFS of 10.0 months vs 4.8 months with TPC (HR, 0.48; 95% CI, 0.36-0.63). For those with IHC 2+/in situ hybridization-negative disease the median PFS was 9.9 months vs 5.1 months, respectively (HR, 0.55; 95% CI, 0.39-0.76).1

Patients age 65 years or older had a median PFS of 11.4 months with trastuzumab deruxtecan vs 6.2 months with TPC (HR, 0.57; 95% CI, 0.36-0.89) and those younger than 65 years had a median PFS of 9.8 months vs 4.6 months, respectively (HR, 0.47; 95% CI, 0.37-0.61). Patients receiving 1 prior line of chemotherapy saw a 48% reduction in the risk of death with trastuzumab deruxtecan (HR, 0.52; 95% CI, 0.39-0.70). The median PFS for trastuzumab deruxtecan vs TPC for these patients was 10.1 months vs 6.4 months, respectively. For those who received 2 prior lines of chemotherapy the median PFS with trastuzumab deruxtecan was 9.7 months vs 4.2 months (HR, 0.49; 95% CI, 0.35-0.68).

A 29% reduction in the risk of disease progression or death was observed with trastuzumab deruxtecan compared with TPC among patients who had baseline CNS metastases (n = 32; HR, 0.71; 95% CI, 0.28-1.80). The median PFS for patients who received trastuzumab deruxtecan was 8.1 months vs 4.8 months with TPC. For those without baseline CNS metastases, a 51% reduction in the risk of disease progression or death was observed (HR, 0.49; 95% CI, 0.39-0.62). The median PFS was 10.1 months vs 5.1 months with trastuzumab deruxtecan and TPC, respectively.1

Finally, for those who did and did not receive prior anthracycline treatment the HRs also favored trastuzumab deruxtecan vs TPC at 0.53 (95% CI, 0.40-0.70) and 0.46 (95% CI, 0.32-0.66).

Objective response rate data were also reported across subgroups for trastuzumab deruxtecan vs TPC as follows1:

CDK4/6 inhibitor use
Yes: 50.6% vs 13.0%
No: 58.3% vs 25.5%

Disease burden
Low: 54.0% vs 15.3%
High: 51.1% vs 17.2%

Rapid progression
Yes: 50.0% vs 0%
No: 52.4% vs 17.0%

HER2 IHC status
IHC 1+: 49.1% vs 16.8%
IHC 2+/ISH–: 56.6% vs 15.6%

Prior lines of chemotherapy
1: 51.1% vs 19.0%
2: 56.6% vs 13.3%

Age
< 65 years: 53.8% vs 14.7%
≥ 65 years: 47.0% vs 20.8%

Baseline CNS metastases
Yes: 55.0% vs 25.0%
No: 51.1% vs 15.9%

Prior anthracycline treatment
Yes: 51.9% vs 16.6%
No: 53.0% vs 12.7%

Safety profiles for patients who did and did not receive CDK4/6 inhibitors and for patients with low and high disease burden were reported and were consistent across patients. For patients who received prior CDK4/6 inhibitors, the rate of grade 3 or higher adverse effects (AEs) was 49.8% with trastuzumab deruxtecan vs 66.1% with TPC. For those who did not receive prior CDK4/6 inhibition, these rates were 57.1% vs 67.4%, respectively.1

The rates of ILD were 12.4% and 11.2% with trastuzumab deruxtecan for those who received and did not receive CDK4/6 inhibitors, respectively.

For patients with low disease burden the rate of grade 3 or higher treatment-emergent AEs was 55.0% vs 67.9% with trastuzumab deruxtecan and TPC, respectively. Among those with high disease burden these rates were 50.9% vs 67.0%, respectively. Rates of ILD with trastuzumab deruxtecan in the low tumor burden and high tumor burden subgroups was 12.8% and 12.2%, respectively.1

Investigators noted that a safety analysis for those with rapid progression was not conducted due to small sample size.1

References

  1. Harbeck N, Modi S, Jacot W, et al. Trastuzumab deruxtecan vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: subgroup analyses from DESTINY-Breast04. Presented at 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX.
  2. Modi S, Jacot W, Yamashita T, et al; DESTINY-Breast04 Trial Investigators. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
Related Videos
Related Content