A paradigm shift in the treatment of metastatic breast cancer20/09/2021
Early stage breast cancer, news from ESMO24/09/2021
Interesting news on metastatic breast cancer, from new options with antibody-conjugated drugs and PD-L1 inhibitors to CDK4/6 inhibitors
Many interesting news, which could change clinical practice in the future, are coming from the numerous clinical studies on breast cancer presented at the ESMO 2021 congress.
Data from KEYNOTE-355 trial show that pembrolizumab added to chemotherapy (woth nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin) gives a significant and clinically meaningful improvement in overall survival vs chemo alone in patients with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer whose tumors expressed PD-L1. The pembrolizumab combination reduced the risk of death by 27% in a disease in which overall survival has remained poor and unchanged for years; now it will be relevant a focus on better selection of patients and a careful evaluation of their eligibility for immunotherapy, for a better use of immune checkpoint inhibitors in this setting, for example being aware of the dynamic nature of PD-L1, that can change with the evolution of the tumor and site of metastatic disease.
Very good results were presented for HR+/HER2- advanced breast cancer too: Monaleesa-2 trial, investigating ribociclib, a CDK4/6 inhibitor, plus letrozole vs letrozole only, showed a significant overall survival benefit for the association (median, 63.9 vs 51.4 months, more than 12 months), with an estimated 6-year overall survival rate of 44.2% for ribociclib vs 32.0%. This is the first report of a statistically significant and clinically meaningful overall survival benefit with a first line CDK4/6 inhibitor in association with aromatase inhibitors in postmenopausal patients with this cancer. ESMO congress featured other studies on CDK4/6 inhibitors in HR+/HER2- advanced breast cancer: PEARL trial final results, that evaluated palbociclib plus endocrine therapy vs capecitabine in patients progressing on aromatase inhibitors, show that despite no survival benefits the combination therapy seems to provide quality of life and tolerability benefits over chemotherapy. Moreover, an analysis of the italian study BioltaLEE shows that thymidine-kinase activity is a new promising prognostic, predictive and monitoring biomarker in patients with HR+/HER2- advanced breast cancer treated with first line ribociclib and letrozole.
For patients with HER2 + metastatic breast cancer, in the TULIP trial [vic-] trastuzumab duocarmazine was compared with physician’s choice chemotherapy in patients who had already received two lines of treatment: progression-free survival was 7 months versus 4.9 for chemotherapy alone, with a safety profile consistent with the drug profile. According to ESMO experts, future research should explore the sequencing of these antibody–drug conjugates to evaluate resistance and optimize antibody–drug conjugate sequencing for patients with breast cancer.