HER2 positive breast cancer: de-escalation of treatment must be personalized

His comments come on the occasion of the presentation of the updated research findings at the first ESMO Breast Cancer Congress 2019, which will take place from May 2 to 4, 2019 in Berlin, Germany.

"The introduction of anti-HER2 treatments has had a significant beneficial effect on survival in early and late positive HER2 bad cancer. It is now necessary to reduce the intensity and side effects of treatment., Said Criscitiello. "However, the priority is to identify which patients might be spared from certain toxic therapies without worsening survival benefits.. "

A de-escalation strategy without chemotherapy in the first-line treatment of HER2-positive metastatic bad cancer was attempted in the PERNETTA trial.¹ As noted earlier, the strategy does not worsen overall survival at two years but dramatically shortens progression-free survival.

The Phase II trial randomized 210 patients to trastuzumab plus pertuzumab alone versus trastuzumab plus pertuzumab in combination with chemotherapy up to progression. After progression, both groups received T-DM1 as second-line therapy. The primary endpoint of 2-year overall survival was achieved by 77% of patients receiving only antibodies and 76% of those also receiving chemotherapy. Progression-free survival after first-line treatment was 8.4 months with antibodies alone and 23.3 months with antibody plus chemotherapy.

New discoveries revealed today at the ESMO Breast Cancer Congress 2019 show that the results were similar regardless of hormone receptor status and that the overall quality of life was also similar between groups during treatment. first intention.² However, based on adverse event and symptom badysis reported by patients, those receiving only antibodies had less hair loss, mouth sores, nausea and fatigue.

The difference in progression-free survival between groups prompted investigators to look for predictors to identify patients likely to receive targeted treatment alone with little or no negative impact on progression-free survival. They use the PAM50 test to profile tumors of all patients participating in the trial.

Professor Jens Huober, first author of Ulm University Hospital (Germany), said:HER2-positive bad cancer tests in the neoadjuvant setting showed that the HER2-enriched subtype is the most sensitive to anti-HER2 treatment. Our hypothesis is that this also applies to the metastatic parameter. If the difference in progression-free survival is smaller in this subtype, omitting chemotherapy in the first line may be a good option for these patients..

Huober said the test was intended to determine whether it was safe to omit chemotherapy when first-line treatment of patients with metastatic bad cancer HER2 positive who received dual anti-HER2 treatment followed by T-DM1. "We looked at two-year overall survival because doctors fear losing their patients quickly if they do not give maximum treatment. Progression-free survival was shorter but did not appear to affect overall long-term survival. The omission of first-line chemotherapy could be considered as an option for patients with low to intermediate tumor burden. However, a phase III trial is needed to definitively prove that patients are not likely to die prematurely if they start using only antibodies.. "

The ESMO spokesman, Criscitiello, stressed that it was important that studies conducted in this area select a specific population in which to attempt to optimize the intensity of treatment. "There was no biological selection of patients in the PERNETTA trial, "Noted Criscitiello, who also emphasized the choice of the main evaluation criterion. "Here we have progression-free survival almost two-fold less than that achieved with chemotherapy. The criterion for evaluating short-term overall survival was not taken into account if a treatment whose effects on long-term survival were significantly demonstrated was rejected. In addition, the size of the sample is very small to detect a difference in overall survival. Avoid chemotherapy in cases of HER2-positive disease is attractive to patients and researchers, but it must be done safely. "

University trials are now crucial in bad cancer, added Criscitiello. "The prognosis of patients with bad cancer has improved considerably thanks to several new treatments available; we could see reduced interest from the industry to invest more in this disease, especially in trials designed with de-escalation attempts. Independent academic essays are very important for investigating research questions of interest to patients and physicians, such as reducing treatment to less toxic and demanding treatments and identifying patients who may be able to get the most out of treatment. such an approach.. "

References