Etienne Brain, MD, PhD, on Breast Cancer: Adjuvant Endocrine Therapy With or Without Chemotherapy in Older Patients

ASTER 70s study is a landmark study, which has been conducted in older women with luminal breast cancer in adjuvant setting questioning the addition of chemotherapy to endocrine treatment. The rationale behind is that the literature is very limited in terms of data published for the use of adjuvant chemotherapy in this situation in older ones. Multimorbidity competes with cancer on outcome and therapeutic ratio is also more narrow because there are higher risk of side effects in this population. This trial screened near 2000 patients with the genomic grade index, the GGI, to assess the aggressivity of the disease and to spare the burden of chemotherapy in those patients with low-GGI tumor, while those with a high-GGI tumor were randomized between endocrine treatment alone as a standard arm versus chemotherapy followed by endocrine treatment. Near 2000 patients enrolled, 1,100 randomized between the two arms. This trial shows, on the primary endpoint, which was overall survival by intent-to-treat analysis, that chemotherapy doesn't add a significant benefit in addition to endocrine treatment. That's the first message of caution from this study. Second one is that we can look at different subgroups and perform also the analysis according to the per protocol concept. This modifies or brings a nuance in the results, but I would say that the final potential benefit on overall survival in this case remains marginal. And in this population of older women, it is a key point and a double cautious message. The next step for this study will be to try to improve the discriminative capacity of this kind of signature to identify those who could benefit still from chemotherapy, despite these global message and results on overall survival. This will be certainly possible with the use of the mass and the volume of data which has been collected in the randomized groups in this study, because there was a longitudinal collection of geriatric data, quality of life data, and treatment acceptability socioeconomic data, which will be very helpful to modelize differently, the prognosis of these ladies. That's in the near future, and I think what brings the most in terms of information ASTER 70s, is that on the provisor that you change a bit of rules for inclusion criteria, because in this study we had very flexible inclusion criteria, we made a focus on quality of life and we use a single informed consent for screening and randomization, on the provisor that you facilitate or you simplify the processes, you can run large studies in a vast population, which is very often not considered for clinical trials left behind.