Commentary: New Drugs, and Exercise, in Breast Cancer January 2023

January 6, 2023|Breast Cancer ICYMI

Clinical Edge Journal Scan: Breast Cancer January 2023 (1 of 11)

The phase 3 DESTINY-Breast03 trial evaluated trastuzumab deruxtecan vs ado-trastuzumab emtansine (T-DM1) in 524 patients with unresectable or metastatic human epidermal growth factor receptor 2–positive (HER2+) breast cancer (BC) previously treated with trastuzumab and a taxane. Results showed that trastuzumab deruxtecan improved survival outcomes compared with trastuzumab emtansine, with median progression-free survival (PFS) of 28.8 months vs 6.8 months (hazard ratio [HR] 0.33 [95% CI 0.26-0.43]; P < .0001). Median overall survival (OS) was not reached in either cohort, with 72 (28%) OS events in the trastuzumab deruxtecan group vs 97 (37%) in the trastuzumab emtansine group (HR 0.64; 95% CI 0.47–0.87]; P = .0037). A manageable safety profile was reported, with a similar number of grade 3 or worse treatment-related adverse events in patients who received trastuzumab deruxtecan vs trastuzumab emtansine (56% vs 52%). Drug-related interstitial lung disease occurred in 15% of patients treated with trastuzumab deruxtecan vs 3% of patients treated with trastuzumab emtansine, with no grade 4 or 5 events in either group.

This is the longest reported median PFS in HER2+ metastatic BC, highlighting the potential of trastuzumab deruxtecan in treating this disease and confirming this drug as the standard of care in the second-line setting.

A cohort study evaluated 315 postmenopausal BC survivors to estimate the association of physical activity with risk for all-cause mortality. Participants were queried about leisure-time physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ), which provided a composite score that categorized exercise patterns as active, moderately active, or insufficiently active at baseline.

Results showed that participants who were active or moderately active had a 60% decreased risk for death compared with insufficiently active participants (active: HR 0.42 [95% CI 0.21-0.85]; moderately active: HR 0.40 [95% CI 0.17-0.95]). A similar mortality risk was reported among participants who were active and those with moderate physical activity levels.

Prior studies¹ have reported similar results, reaffirming the value of exercise in BC survivors and highlighting the need to incorporate physical activity as part of survivorship care plans.

The phase 3 SOPHIA study randomized 536 patients with HER2+ advanced BC who had received two or more prior anti-HER2 regimens to margetuximab plus chemotherapy vs trastuzumab plus chemotherapy. Final OS results after a median follow-up of 20.2 months showed no benefit in OS observed with margetuximab vs trastuzumab (median OS 21.6 months vs 21.9 months; HR 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients vs trastuzumab (median OS 23.6 vs 19.2 months; HR 0.72; 95% CI 0.52-1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients vs margetuximab (median OS 31.1 vs 22.0 months; HR 1.77; 95% CI 1.01–3.12). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Further studies to evaluate the role of margetuximab in patients with HER2+ BC with different CD16A allelic variants are warranted.

Additional References

Cannioto RA, Hutson A, Dighe S, et al. Physical activity before, during, and after chemotherapy for high-risk breast cancer: Relationships with survival. J Natl Cancer Inst. 2021;113:54-63. Doi:10.1093/jnci/djaa046