Kadcyla (ado-trastuzumab emtansine, or T-DM1) may benefit HER2-positive metastatic breast cancer patients whose disease continues to progress despite prior treatment with Herceptin (trastuzumab) and Perjeta (pertuzumab), according to the results of a retrospective study.
The results, “T-DM1 Activity in Metastatic Human Epidermal Growth Factor Receptor 2–Positive Breast Cancers That Received Prior Therapy With Trastuzumab and Pertuzumab,” published in the Journal of Clinical Oncology, demonstrate a meaningful tumor control rate in patients who received Perjeta prior to Kadcyla.
Although Herceptin has markedly improved the treatment of HER2-positive breast cancer, most patients eventually require other treatments for their disease progression. Several HER2-directed therapies, including Tyverb (lapatinib), Perjeta, and Kadcyla, have been developed for these people.
Kadcycla was approved by the U.S. Food and Drug Administration (FDA) as a second-line treatment for people with HER2-positive metastatic breast cancer, who had previously received standard therapy with Herceptin and a taxane, in 2013. However, Perjeta was later added to standard first-line treatment as part of neoadjuvant therapy, and the need arose to assess the activity of Kadcycla in patients previously exposed to Perjeta.
Researchers used data from HER2-positive metastatic breast cancer patients at The Ohio State University Comprehensive Cancer Center, Yale Cancer Center, and The University of Texas MD Anderson Cancer Center to assess the outcomes of patients who received Kadcycla following therapy with Perjeta.
The study’s efficacy measures included tumor response; prolonged duration of therapy, defined as Kadcycla therapy lasting six months or longer; minimal benefit, defined as stable disease as initial response to Kadcycla but discontinuation before six months; and progressive disease, indicated by new or enlarging lesions on tumor imaging.
Among the breast cancer patients studied, 82 had been given Perjeta prior to single therapy with Kadcycla, and data on 78 of them were available for outcome analysis. Results revealed that only 32% of patients received Kadcycla as a first- or second-line therapy, and 48% received it as fourth-line treatment or later. “In current practice, many patients were diagnosed with metastatic disease before approval of either pertuzumab or T-DM1, which results in a population that has received multiple prior lines of therapy before it receives these newer HER-2–targeted therapies,” Lajos Pusztai, MD, medical oncologist at Yale Cancer Center, and colleagues wrote.
After examining the outcomes, researchers found a 17.9% tumor response rate and that 30.8% of patients had prolonged duration on therapy (six or more months). Given that medical oncologists usually continue treatment with a specific drug until disease progression or the development of severe side effects, therapy duration is a measure of clinical benefit and tolerability. Median duration of Kadcycla therapy was four months.
Data collected also showed that 12.8% of patients had a minimal benefit response, and 50% has progressive disease. However, more than 84% of patients eventually discontinued Kadcycla due to disease progression, but only 10% discontinued due to toxicity.
“Tumor response rates were lower than in prior reports of trastuzumab-resistant, HER2-positive MBC [metastatic breast cancer], but one third of patients received therapy with T-DM1 for ≥ 6 months, which suggests a clinically relevant benefit in patients who received prior pertuzumab,” the researchers concluded.
“Positive results in refractory metastatic breast cancer and recent reports of significant efficacy in the neoadjuvant setting with T-DM1 [Kadcycla], coupled with excellent tolerability, gives cause for optimism for future incorporation of this drug in early breast cancer, with hopes for an improved therapeutic index,” Reshma L. Mahtani, DO, and Charles L. Vogel, MD, both of Sylvester Comprehensive Cancer Center in Florida, wrote in an accompanying editorial.