Published in the Journal of the National Cancer Institutethe results of the ASPIRE trial concern 29 patients with HR-positive and HER2-positive metastatic breast cancer. After nearly three and a half years of follow-up, almost 93% of them were still alive. An interesting signal, but which does not yet allow us to shake up treatment standards.
What if chemotherapy wasn’t always the first step?
When breast cancer becomes metastatic, daily life can suddenly become organized around treatments: consultations, infusions, examinations, side effects. For some patients, the prospect of chemotherapy constitutes an additional ordeal, with fatigue, blood or digestive disorders and the possible consequences on quality of life.
It is precisely this question that researchers at the Icahn School of Medicine at Mount Sinai, in New York, wanted to explore: can we control the disease without resorting to chemotherapy from the start of treatment?
They were interested in a particular subtype: breast cancers HR positive and HER2 positivethat is to say whose tumor cells have hormonal receptors and a significant quantity of the HER2 protein. This profile represents approximately 10% of breast cancers.
The ASPIRE trial evaluated a combination of four treatments:anastrozolehormone therapy,
palbociclibwhich blocks the CDK4/6 proteins involved in cell multiplication, and two treatments targeting HER2, the trastuzumab and the
pertuzumab.
The objective: to act simultaneously on several mechanisms that allow the tumor to develop, while avoiding chemotherapy.
29 women, and results that attract attention
The phase 1/2 study was conducted at five centers affiliated with Mount Sinai, NYU Langone Health and Columbia University. The patients had not yet received any treatment for their metastatic disease. Before evaluating the combination, the researchers notably determined the maximum tolerated dose of palbociclib, set at 125 mg.
The results then provided a first particularly encouraging signal. During the first six months,
97% of participants obtained clinical benefit. Median progression-free survival reached
24.9 months : in other words, half of the patients lived at least this duration without worsening of their illness.
After a median follow-up of approximately 39 monthsnext to 93% of participants were still alive. One patient was still receiving this treatment more than six years after the start of the protocol.
“This study shows that a chemotherapy-free treatment approach can produce durable responses while maintaining a manageable safety profile for many patients with this metastatic breast cancer subtype.”explains Amy Tiersten, senior lead author of the study. “Although these results need to be confirmed in larger randomized clinical trials, they suggest that some patients may ultimately have an effective alternative to chemotherapy as their first treatment..
These results therefore do not mean that chemotherapy could disappear. Rather, they suggest that some patients could, in the future, have another first-line option.
Less chemotherapy, but also fewer daily constraints?
The benefit of this strategy is not only measured in months without progress. For patients, the way a treatment fits into daily life also matters.
In the trial, the combination relied mainly on a drug taken orally and subcutaneous injections, which could limit some hospital visits compared to treatments requiring chemotherapy infusions.
“The challenge in treating this type of breast cancer is to find the balance between effectiveness and quality of life.”underlines Rima Patel, first author of the study. “Many patients, especially the elderly or those with other medical conditions, may not be ideal candidates for chemotherapy. A targeted regimen that can be administered primarily orally and by subcutaneous injection could offer a more convenient option while reducing some of the burden associated with chemotherapy.”.
The strategy is, however, not without its side effects. The most frequent were the
neutropeniathat is to say a reduction in neutrophils, white blood cells essential for defense against certain infections, as well as a reduction in white blood cells, diarrhea and anemia.
Only one treatment discontinuation linked to adverse effects was reported and no deaths attributable to treatment occurred.
A real hope, but still far from changing practices
This is where researchers urge caution. The study only covers 29 patients and does not include a comparative group receiving the treatment currently considered standard. It is therefore impossible, at this stage, to state that this combination is superior to chemotherapy associated with anti-HER2 treatments. The results should be considered as
hypothesis generatorsuntil their confirmation in larger randomized trials.
The researchers plan to continue their work to determine whether this strategy can really improve results compared to standard treatments. For patients who, tomorrow, could benefit from effective treatment without chemotherapy, this avenue could represent much more than a change in treatment: the possibility of treating the disease while further preserving a daily life already profoundly disrupted by cancer.