A four-drug regimen with no chemotherapy in it held advanced breast cancer in check for a median of 24.9 months, according to the phase 1/2 ASPIRE trial published in the Journal of the National Cancer Institute and announced by Mount Sinai on August 20, 2026. Researchers at the Icahn School of Medicine at Mount Sinai gave anastrozole, palbociclib, trastuzumab and pertuzumab as the very first treatment to 29 patients with hormone receptor (HR)-positive, HER2-positive metastatic breast cancer, a subtype making up roughly 10 percent of breast cancers that is usually treated up front with HER2-targeted drugs plus chemotherapy.
Key takeaways
- 28 of 29 patients, or 97 percent, had their cancer shrink or hold steady through the first six months.
- The cancer stayed under control for a median of 24.9 months, and median survival had not been reached at about 39 months of follow-up.
- There was no comparison group and only 29 patients, so this points toward a larger trial rather than changing care today.
What the study found
The trial ran across five clinical sites affiliated with Mount Sinai, NYU Langone Health and Columbia University. Investigators first worked out the palbociclib dose. No dose-limiting toxicities showed up at 100 mg or 125 mg, so 125 mg became the maximum tolerated dose. Twenty-three more patients were then enrolled, giving 29 in the response-evaluable group.
The main result was the clinical benefit rate, the share of patients whose cancer shrank or at least stopped growing in the first six months. That was 97 percent, 28 of 29 patients. The true figure is very likely between 82 and 99 percent (95% CI: 82 to 99), a wide spread that comes with counting only 29 people.
At a median follow-up of 45.3 months, the median time before the cancer grew again was 24.9 months. The real median is very likely between about 17 and 45 months (95% CI: 17.2 to 44.8). Median overall survival had not been reached at 39.4 months of follow-up, meaning fewer than half of the patients had died by that point. One patient has stayed on the regimen more than six years.
Severe (grade 3 to 4) treatment-related side effects hit 62 percent of patients, 18 of 29, and most were blood-count problems. The most common side effects overall were neutropenia, leukopenia, diarrhea and anemia. One patient stopped treatment because of side effects, and there were no treatment-related deaths.
Dr. Kumar’s take
The phrase “chemotherapy-free” is doing a lot of work in the coverage of this trial. The leading side effects were neutropenia and leukopenia, the low white-blood-cell counts patients associate with chemo more than with anything else, plus anemia. Nearly two thirds had a grade 3 or 4 event. The honest claim is a different side-effect profile, not a gentler one. What patients plausibly avoid is hair loss, neuropathy and infusion-chair time, since this regimen is mostly a pill plus injections. That is worth something, and it is not the same as an easy treatment.
The other number a wire summary skips is the denominator. Twenty-nine patients, no control arm, and the researchers say so themselves: the study was relatively small, did not compare the regimen with current standard treatment, and should be read as hypothesis-generating.
ASPIRE asks a narrow question: can you skip the chemotherapy induction step entirely and start with the targeted combination? That is a sequencing question, and 29 uncontrolled patients cannot answer it. The investigators are planning studies against standard of care, which is the right next move.
What it means for you
If you or someone you know has HR-positive, HER2-positive metastatic breast cancer, this is worth raising with an oncologist, particularly for an older patient or someone with other conditions who is a poor candidate for chemotherapy. It is a trial result, not a standard option, so the practical question is whether a trial slot is open.
Do not read “chemo-free” as “side-effect free.” Blood counts still need watching on this regimen.
Related: daily vitamin D nearly doubled chemo’s power to clear breast cancer and GLP-1 drugs like Ozempic linked to better breast cancer survival.
Pfizer, which makes palbociclib, provided the drug and funding for the trial.