Home · Health · Oct 8 archive
FDA Approves Tukysa for First-Line Maintenance in HER2-Positive Breast Cancer
Confirmed
In Short: The FDA has approved Pfizer's Tukysa in combination with trastuzumab and pertuzumab as maintenance treatment for HER2-positive metastatic breast cancer.
The FDA has approved Pfizer's Tukysa (tucatinib) in combination with trastuzumab and pertuzumab as maintenance treatment for adults with unresectable locally advanced or metastatic HER2-positive breast cancer who have completed induction therapy, the company announced on October 7.
Aamir Malik, executive vice president and chief U.S. commercial officer of Pfizer, said, “Since its first approval in 2020, Tukysa has become an important treatment for patients with second-line HER2+ metastatic breast cancer. Today's FDA approval marks the next chapter for Tukysa, bringing it into the front-line maintenance setting and offering patients a chemotherapy-free option that can help delay disease progression after initial treatment.”
The approval is based on the HER2CLIMB-05 trial, which included 654 patients with HER2-positive metastatic breast cancer with or without brain metastases. The trial evaluated tucatinib versus placebo, each combined with trastuzumab and pertuzumab, as first-line maintenance therapy.
Jennifer Taylor, a 41-year-old event planner, has been undergoing treatment that includes 12 weeks of initial chemotherapy, a double mastectomy, 20 rounds of radiation, chemically induced menopause, and an additional chemotherapy treatment called ENHERTU.
Taylor said, “There really isn’t a version of my life that doesn’t have her in it,” referring to her best friend Adrien Finkel, who has been helping her navigate her breast cancer diagnosis.
The standard approach for advanced/metastatic HER2-positive disease has been upfront chemotherapy along with trastuzumab and pertuzumab, both HER2-targeted monoclonal antibodies, followed by maintenance with both antibodies until progression.
In the HER2CLIMB-05 trial, overall, 42% of tucatinib patients had grade ≥ 3 adverse events compared with 24% of patients in the placebo arm; 13% of tucatinib subjects stopped treatment due to adverse events, most commonly hepatic side effects.
Serious hepatotoxicity occurred in 3.9% of patients, including one fatal case of drug-induced liver injury, and hepatotoxicity led to discontinuation in 8%. The label carries a boxed warning for severe hepatotoxicity and calls for liver function testing before and during treatment.
HER2 is overexpressed in up to 15% to 20% of breast cancers and is associated with poor prognosis; Pfizer cites an estimated five-year survival of 41% to 47%, depending on hormone receptor status.
The HER2CLIMB-05 findings support TUKYSA plus trastuzumab and pertuzumab as a chemotherapy-free maintenance strategy that allows us to target HER2-positive tumors from multiple angles and can help prolong disease control.
The new approval was based on the HER2CLIMB-05 trial with 654 patients with HER2-positive metastatic breast cancer with or without brain metastases.
Eligibility criteria included having no evidence of progression after induction treatment with four to eight cycles of trastuzumab, pertuzumab, and a taxane.
What this adds
In mice with cancer-driving mutations, tumors formed in the liver and skeletal muscle but not the heart.
The heart is among the organs least likely to develop cancer, a long-standing biological puzzle.
The HER2CLIMB trial included 612 patients, and Pfizer describes the drug as a National Comprehensive Cancer Network Category 1 option for second-line and later use.
Background
The FDA has approved pirtobrutinib (Jaypirca) for adults with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) without 17p deletion.
The Food and Drug Administration has approved daraxonrasib, a new drug that could significantly improve survival rates for pancreatic cancer patients.
What's confirmed
- The FDA has approved Pfizer’s Tukysa (tucatinib) in combination with trastuzumab and pertuzumab as maintenance treatment for adults with unresectable locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer who have completed induction therapy, the company announced Oct. 7. 1 The decision moves the oral therapy from later-line use into the first-line setting, where it is added to an established antibody pair.
What's still developing
- Cardiac metastases are found in up to 18% of autopsies, but these metastatic tumors are often small, incidental, and asymptomatic.
- A recent Science study offers a possible explanation.
- Lung cancer cells grew rapidly in a mechanically unloaded transplanted heart but far less in the same mouse's native heart.
- Inactivating it allows cancer cells to resume proliferating despite mechanical load.
- "Why Does the Heart Rarely Develop Cancer?"
- In mice with cancer-driving mutations, tumors formed in the liver and skeletal muscle but not the heart.
- The heart is among the organs least likely to develop cancer, a long-standing biological puzzle.
- That approval was based on the 612-patient HER2CLIMB trial. 4 Pfizer describes the drug as a National Comprehensive Cancer Network Category 1 option for second-line and later use and reports five approved breast cancer medicines and one biosimilar. 1 Pfizer said safety was generally consistent with the known profile of Tukysa, except for increased severity of hepatotoxicity.
- 1 The results were published in the Journal of Clinical Oncology and presented at the 2025 San Antonio Breast Cancer Symposium.
- “I had spent the first days after my diagnosis desperately searching the internet for someone who looked like me and whose life still looked vaguely recognizable. I wanted to know what chemo actually looked like. I wanted to know if I would ever laugh or go to dinner or wear something I liked or feel like myself again. And so much of what I found made me feel like my life was already over,” she continues.
- In May, the Food and Drug Administration (FDA) approved Datroway (datopotamab deruxtecan) as a new option for previously untreated patients with inoperable or metastatic triple-negative breast cancer (TNBC) who are not candidates for checkpoint inhibitor immunotherapy.
- “For patients with metastatic TNBC, a new first-line treatment option offers optimism to a community with historically few choices,” says Ricki Fairley, cofounder and CEO of TOUCH, the Black Breast Cancer Alliance.