A chemotherapy-free combination of four targeted drugs kept an aggressive form of metastatic breast cancer in check for close to two years in a small early-stage trial, researchers at the Icahn School of Medicine at Mount Sinai reported this month.
The trial, called ASPIRE, was aimed at women with HR-positive, HER2-positive metastatic breast cancer. That subtype accounts for a large share of HER2-positive cases. HER2-positive tumors make up about 14 percent of breast cancers in women, and most of those are also hormone receptor-positive.
The regimen paired anastrozole, an estrogen-blocking hormone pill, with palbociclib, a targeted pill that stalls cancer cell division, and two anti-HER2 antibodies given by injection, trastuzumab and pertuzumab.
What the phase 1/2 trial actually tested
About 30 women whose cancer had spread and who had not yet been treated for it joined the multicenter trial run through Mount Sinai, NYU Langone Health and Columbia University. Instead of the intravenous chemotherapy that anchors current first-line treatment, they received an all-oral and injection-based regimen.
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When the trial was first reported at the San Antonio Breast Cancer Symposium in late 2023, the combination produced a clinical benefit rate of 97 percent and a median progression-free survival of 21.2 months, according to CancerNetwork. The now-published journal paper reflects longer follow-up.
Amy Tiersten, professor of medicine at Mount Sinai and senior author of the trial, told CancerNetwork the appeal of the approach lies in what patients can avoid.
"It's hugely important if we can have that kind of clinical benefit rate and the duration of the response and have patients avoid the toxicities of chemotherapy such as hair loss, neutropenia, fever, and nausea," Tiersten said.
How the drugs work together
Endocrine therapies such as anastrozole block the hormone signals that feed HR-positive cancers. Trastuzumab and pertuzumab attach to the HER2 protein on tumor cells and interrupt the growth signals it sends. Palbociclib works inside the cell, blocking enzymes called CDK4 and CDK6 that cancer cells depend on to divide.
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The current standard first-line treatment for HR-positive, HER2-positive metastatic breast cancer, based on the CLEOPATRA trial, combines trastuzumab and pertuzumab with the chemotherapy drug docetaxel. ASPIRE swaps in hormone therapy and a targeted pill in place of that chemotherapy.
Side effects were not zero
Even without chemotherapy, the four-drug regimen had a meaningful side-effect burden. The most common events reported were neutropenia in 87 percent of patients, diarrhea in 83 percent, leukopenia in 77 percent, anemia in 70 percent and fatigue in 60 percent, according to Healio's coverage of the trial.
Grade 3 or 4 neutropenia, a serious drop in infection-fighting white blood cells, affected about 46 percent of participants. No treatment-related deaths were reported.
For comparison, the most common side effect of chemotherapy is fatigue, the National Cancer Institute says, with hair loss, mouth sores and nausea also frequent.
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An early finding, not a new standard
ASPIRE is a small phase 1/2 trial. The results are promising but need to be confirmed in larger randomized studies before this regimen could become a routine alternative to chemotherapy in this subgroup. Women with HR-positive, HER2-positive metastatic breast cancer who want to know whether a chemotherapy-free approach might fit their situation should raise it with their oncologist, who can weigh eligibility, other conditions and current treatment options.
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This article is made and published by Jesper Bengtson, who may have used AI in the preparation.