Enhertu Bests Standard of Care in Potentially Preventing Disease Progression, Death in Previously Treated HER2-Positive Metastatic Breast Cancer

Certain patients with metastatic breast cancer may benefit from Enhertu compared with standard of care with Kadcyla despite higher rates of side effects including lung inflammation and interstitial lung disease.

Treatment with Enhertu (trastuzumab deruxtecan) reduced the risk for disease progression or death compared with Kadcyla (trastuzumab emtansine) in patients with HER2-positive metastatic breast cancer who were previously treated with trastuzumab and a taxane, according to recent study results.

“(Enhertu) is an effective new treatment for patients with HER2-positive metastatic breast cancer who have been previously treated with trastuzumab and a taxane, as well as with pertuzumab (Perjeta) when available,” Dr. Javier Cortes Castan, head of the breast cancer program at Vall d’Hebron University Hospital in Barcelona, Spain, and colleagues wrote in the study published in The New England Journal of Medicine.

Findings from the DESTINY-Breast03 trial also demonstrated that patients treated with Enhertu were more likely to have side effects including interstitial lung disease and pneumonitis (lung inflammation).

“Most of the drug-related (side effects) of interstitial lung disease or pneumonitis in this trial were of grade 1 (mild) or 2 (moderate), with only two events reported as grade 3 (severe),” the researchers wrote.

In this phase 3 trial, researchers analyzed data from 524 patients with HER2-positive metastatic breast cancer who were previously treated with trastuzumab and a taxane. These patients were assigned either Enhertu (261 patients) or Kadcyla (263 patients). Of note, Kadcyla is currently the standard treatment for this particular patient population.

Researchers assessed several factors throughout this trial including progression-free survival (the time during and after treatment when a patient lives with cancer without disease spread), overall survival (the time when a patient with cancer is still alive), objective response (a measurable response to treatment) and safety.

At 12 months, more patients treated with Enhertu were alive without disease progression compared with those treated with Kadcyla (75.8% versus 34.1%). When disease progression was taken out of consideration, 94.1% of patients in the Enhertu group were alive at 12 months compared with 85.9% of those in the Kadcyla group.

“Across all the evaluations of progression-free survival (central review, investigator review and subgroup analysis), the hazard ratios indicate a reduction of approximately 70% in the risk of disease progression or death with (Enhertu) as compared with (Kadcyla),” the researchers wrote.

Researchers observed an overall response to treatment, which pertains to the percentage of patients with a partial or complete response to a particular treatment), in 79.7% of patients assigned Enhertu versus 34.2% of those assigned Kadcyla.

Side effects of any severity related to a particular drug occurred in 98.1% of patients in the Enhertu group and 86.6% of those in the Kadcyla group. In addition, side effects associated to an assigned drug that was considered severe or life-threatening occurred in 45.1% of patients treated with Enhertu and 39.8% of those treated with Kadcyla. Although more patients assigned Enhertu had interstitial lung disease or pneumonitis from treatment compared with those assigned Kadcyla (10.5% versus 1.9%), none of these events were considered life-threatening or fatal.

“The incidence of interstitial lung disease and pneumonitis was numerically lower in the current trial than in other clinical trials of (Enhertu),” the study authors wrote. “This difference in results may be explained by the fact that the patients in this trial received an earlier line of therapy and the fact that there is increased recognition of these (side effects).”

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