Study: Combining two anti-HER2 drugs improves outcomes more effectively than one
Summary
Combining two anti-HER2 drugs increased the time until cancer returned for people with locally advanced or metastatic HER2-positive breast cancer compared to people who received just one anti-HER2 drug. People whose breast cancer had metastasized to the brain also benefitted from the two combined drugs. (Posted 9/17/24)
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Most relevant for: People with Her2-positive metastatic breast cancer.
It may also be relevant for:
- people with Her2-positive cancer
Relevance: High
Strength of Science: High
Research Timeline: Post Approval
What is this study about?
This study included people with advanced or HER2-positive breast cancer and compared the outcomes of those who received two combined drugs—Tukysa (tucatinib) and Kadcyla (T-DM1)— compared to those who received Kadcyla alone.
Why is this study important?
Previously, the HER2CLIMB trial found that adding Tukysa to Herceptin and chemotherapy significantly improved both the time until cancer came back and overall survival in people with HER2-postive advanced breast cancer. Even people whose cancer had metastasized benefitted from this combination. This trial led to the 2020 approval of combining Tukysa and Herceptin with chemotherapy.
However, not all patients have a long response time to Tukysa. For this reason, researchers wanted to test whether a different combination of drugs would boost the benefit of anti-HER2 therapies and delay disease progression.
When breast cancer spreads, it often does so to the brain. Few options exist for the successful treatment of breast cancer brain metastases. This study is one of the few large breast cancer studies designed to evaluate new drugs in patients with brain metastases.
What are the anti-HER2 drugs, Tukysa and Kadcyla?
What is Tukysa?
Tukysa (tucatinib) targets , a protein found on the surface of some cancer cells. Tukysa has been shown to slow the progression of breast cancer, even in the brain, unlike most other anti-HER2 drugs. For more on Tukysa, read our XRAY reviews here and here.
What is Kadcyla?
Kadcyla (T-DM1) also targets . It works by binding to and delivering chemotherapy. Kadcyla is approved to treat both and HER2-positive breast cancer. For more on Kadcyla, read our XRAY review here.
Study findings
HER2CLIMB-02
This trial enrolled 463 people with advanced or HER2-positive breast cancer that could not be surgically removed. Participants were randomly assigned to receive Tukysa plus Kadcyla (228) or Kadcyla alone (235). Among participants, 44 percent had brain metastases when they entered the trial.
Among all participants:
- The time until cancer worsened was 2 months longer in people who were treated with both drugs compared to people treated with Kadcyla alone.
- The median time until cancer worsened was 9.5 months for people who were treated with both drugs compared to 7.4 months for patients treated with Kadcyla alone.
Among participants with brain metastases:
- The time until cancer worsened was 2 months longer in people who were treated with both drugs compared to people treated with Kadcyla alone.
- The median time until cancer worsened was 7.8 months for people treated with both drugs, compared to 5.7 months for those treated with Kadcyla alone.
These results reflect improved outcomes for study participants who were treated with Tukysa and Kadcyla compared to those who were treated with Kadcyla alone. Overall survival data is not yet available.
Side effects were higher among people treated with both drugs compared to Kadcyla alone. This resulted in more dose adjustments and stopped treatment in people who had both drugs. However, the side effects were largely manageable.
Most side effects that occurred were not severe. These included:
- diarrhea
- hand-foot syndrome
- nausea
- fatigue
- vomiting
While these events were similar to the effects that occur with related drugs, they appeared less frequently with Tukysa (tucatinib), suggesting that Tukysa may be a better choice for breast cancer treatment.
What does this mean for me?
If you have metastatic breast cancer that has worsened, especially if it has spread to your brain, you may have a new treatment option. Ask your healthcare provider if the combination of Tukysa and Kadcyla may be right for you.
References
Hurvitz S, Loi S, O’Shaughnessy J, et al. HER2-CLIMB-02: , double-blind, phase 3 trial of tucatinib and trastuzumab emtansine for previously treated metastatic breast cancer. 2023 San Antonio Breast Cancer Symposium. Abstract GS01-10. Presented December 6, 2023.
Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for metastatic breast cancer. N Engl J Med. 2020; 382:597-609.
Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.
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posted 9/17/24
The following organizations offer peer support services for people with, or at high risk for breast cancer:
- FORCE peer support:
- Our Message Boards allow people to connect with others who share their situation. Once you register, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Our Peer Navigation Program will match you with a volunteer who shares your mutation and situation.
- Connect online with our Private Facebook Group.
- Join our virtual and in-person support meetings.
- Other organizations that offer breast cancer support:
Updated: 05/07/2024
The following studies look at treatment for people with HER2-positive breast cancer.
- NCT05458674: Tucatinib+Trastuzumab+Eribulin in HER2+ MBC. This study evaluates the safety and efficacy of the three-drug combination of tucatinib, trastuzumab and eribulin in patients with unresectable HER2-positive breast cancer after prior treatment with a taxane, trastuzumab and T-DM1.
- NCT06100874: A Single-arm Phase II Trial of SAcituzumab Govitecan and Trastuzumab for HER2+ Breast Cancer After Trastuzumab dEruxtEcaN (SATEEN). This study evaluates the safety and effectiveness of sacituzumab govitecan with trastuzumab (Herceptin, Herceptin Hylecta, or trastuzumab biosimilar) in HER2+ breast cancer.
- NCT03368729: in Combination With Trastuzumab in HER2+ Breast Cancer. This study evaluates the safety and tolerability of the niraparib combined with anti-HER2 agent trastuzumab for patients with HER2-positive breast cancer.
- NCT06435429: A Study Comparing the Efficacy and Safety of Zanidatamab to Trastuzumab, Each in Combination With Physician's Choice Chemotherapy, for the Treatment of Participants With HER2-positive Breast Cancer. This study evaluates the safety and effectiveness of zanidatamab combined with chemotherapy compared to trastuzumab (Herceptin) combined with chemotherapy to treat participants with HER2-positive breast cancer who have progressed on or are intolerant to previous T-DXd treatment.
- NCT05378464: Adoptive T Cell Therapy Following HER2-Pulsed Dendritic Cell Vaccine & Pepinemab /Trastuzumab in Patients w/ HER2+ Breast Cancer. This study tests the safety of Adoptive T-Cell therapy following the Dendritic Cell (DC1) vaccine given in combination with pepinemab added to standard-of-care therapy trastuzumab for people with breast cancer.
- NCT05894239: A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus in Combination With Phesgo in Participants With PIK3CA-Mutated Locally Advanced or Breast Cancer. This study looks at the safety and effectiveness of inavolisib combined with Phesgo (pertuzumab, trastuzumab and rHuPH20 injection) compared with combined with Phesgo for after induction therapy for participants with previously untreated advanced breast cancer (ABC).
Other clinical trials for people with breast cancer can be found here.
Updated: 09/12/2024