Tukysa Plus Kadcyla Better Than Kadcyla Alone for Metastatic Breast Cancer
Combining Tukysa (chemical name: tucatinib) with Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine) resulted in better progression-free survival for people diagnosed with previously treated, locally advanced or metastatic HER2-positive breast cancer than Kadcyla alone, according to a study.
Advanced-stage breast cancer is either locally advanced or metastatic:
Locally advanced breast cancer has spread to tissue near the breast, but not to parts of the body away from the breast.
Metastatic breast cancer has spread to parts of the body away from the breast, such as the bones or liver.
Progression-free survival is how long a person lives without the cancer growing.
The research was presented on Dec. 6, 2023, at the San Antonio Breast Cancer Symposium.
Read a media release and the abstract of “HER2CLIMB-02: Randomized, Double-Blind Phase 3 Trial of Tucatinib and Trastuzumab Emtansine for Previously Treated HER2-Positive Metastatic Breast Cancer.”
Why do the study?
Results from the HER2CLIMB study showed that adding Tukysa to the standard-of-care regimen for locally advanced or metastatic HER2-positive breast cancer — Herceptin (chemical name: trastuzumab) and Xeloda (chemical name: capecitabine) — improved progression-free and overall survival, including in people with brain metastases.
Overall survival is how long a person lives, whether or not the cancer grows. Progression-free survival is how long a person lives without the cancer growing.
“HER2-positive breast cancer has a predilection to spread to the brain, and when this occurs, prognosis is poor,” said Sara A. Hurvitz, MD, who presented the research. Dr. Hurvitz is professor and head of the Division of Hematology and Oncology at the University of Washington Department of Medicine and senior vice president and director of the Clinical Research Division at Fred Hutchinson Cancer Center. “Few options exist for the successful management of breast cancer brain metastases, making this an area of unmet need.”
The study was designed in part to meet this need and provide more treatment options for metastatic breast cancer. Since Tukysa made Herceptin and Xeloda more effective, the researchers wanted to see if adding Tukysa to Kadcyla also would improve outcomes.
About the study
Called HER2CLIMB-02, the study included 463 people diagnosed with locally advanced or metastatic HER2-positive breast cancer that had previously been treated with Herceptin (chemical name: trastuzumab) and a taxane chemotherapy medicine, such as Taxol (chemical name: paclitaxel).
The people joined the study between October 2019 and June 2022.
Nearly half the people – 44.1% – had active or stable brain metastases when they joined the study.
The researchers assigned the people to receive one of two treatments:
228 people received Tukysa twice a day, plus Kadcyla on day one of a 21-day cycle
235 people received Kadcyla plus a placebo, pills that looked just like Tukysa but contained no medicine
Tukysa is a pill taken by mouth. Kadcyla is given intravenously, which means the medicine is delivered directly into your bloodstream through an IV or a port.
Half the people were followed for more than two years and half were followed for a shorter period of time.
The risk of the cancer growing or a person dying from breast cancer was 24.1% lower in people who received Tukysa plus Kadcyla compared to people who received Kadcyla alone.
Overall, progression-free survival was:
9.5 months for people who received Tukysa and Kadcyla
7.4 months for people who received Kadcyla alone
Among people with brain metastases, progression-free survival was:
7.8 months for people who received Tukysa and Kadcyla
5.7 months for people who received Kadcyla alone
Tukysa side effects
Although adding Tukysa to Kadcyla did improve progression-free survival, people who received Tukysa along with Kadcyla also had more side effects:
65.4% of people on Tukysa and Kadcyla had nausea compared to 49.4% of people on Kadcyla alone
56.7% of people on Tukysa and Kadcyla had diarrhea compared to 26.6% of people on Kadcyla alone
48.9% of people on Tukysa and Kadcyla had fatigue compared to 37.3% of people on Kadcyla alone
Tukysa also caused more grade 3 or higher (the most serious) side effects, including liver problems:
16.5% of people on Tukysa and Kadcyla had serious liver problems
2.6% of people on Kadcyla alone had serious liver problems
Nearly twice as many people on Tukysa and Kadcyla had side effects that led to them stopping treatment:
22.1% of people on Tukysa and Kadcyla stopped treatment because of side effects
11.6% of people on Kadcyla alone stopped treatment because of side effects
Side effects led to death for three people on Tukysa and Kadcyla and two people on Kadcyla alone.
Dr. Hurvitz pointed out that while the rate of side effects was higher in people receiving Tukysa, they were mostly manageable with careful monitoring and treatment, including dose reductions.
“This study is one of very few large breast cancer studies prospectively designed to evaluate novel systemic therapies in patients with brain metastases,” Dr. Hurvitz said. “While there is much interest in improving outcomes for patients with HER2-positive breast cancer brain metastases, most studies evaluating systemic agents have been limited by a small size, a retrospective design, or an exploratory analysis of a larger study.”
What this means for you
If you’ve been diagnosed with advanced-stage HER2-positive breast cancer that has grown on other treatments — especially if you have brain metastases — it makes sense to talk to your doctor about this study and ask if the Kadcyla and Tukysa combination might be right for your unique situation.
But, while the results of this study are promising, there are several points to keep in mind.
It’s not clear whether the combination of Tukysa and Kadcyla will improve overall survival. The study hasn’t gone on long enough for that information to be analyzed.
This study wasn’t designed to compare the combination of Tukysa and Kadcyla to the combination of Tukysa, plus Herceptin and Xeloda. So it’s not clear which combination might be more beneficial.
This study didn’t compare Tukysa and Kadcyla to any regimen containing Enhertu, also called T-DXd (chemical name: fam-trastuzumab-deruxtecan-nxki). Results from the DESTINY-Breast03 study found that Enhertu more than doubled the 12-month progression-free survival rate compared to Kadcyla when used as a second-line treatment in people diagnosed with metastatic, HER2-positive breast cancer. These results led to Enhertu being the preferred second-line treatment for this type of breast cancer. Dr. Hurvitz explained that there have been no head-to-head studies done comparing Tukysa and Enhertu, but that Tukysa has the most evidence for people with brain metastasis.
Listen to the episode of The Breastcancer.org Podcast featuring Dr. Hurvitz discussing the results of the DESTINY-Breast03 study.
Enhertu Offers Better Overall Survival Than Kadcyla for Metastatic HER2-Positive Breast Cancer
Dec 9, 2022— Last updated on February 9, 2024 at 5:57 PM
This Research News story is made possible, in part, by a grant from Lilly.