Study: Combining two anti-HER2 drugs improves outcomes more effectively than one

Relevance: High

Strength of Science: High

Research Timeline: Post Approval

Relevance Rating Details

What is this study about?

This study included people with advanced or metastatic HER2-positive breast cancer and compared the outcomes of those who received two combined HER2 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 FDA 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 HER2-positive 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 HER2, 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 HER2. It works by binding to HER2 and delivering chemotherapy.  Kadcyla is approved to treat both early-stage and metastatic 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 metastatic 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.