Great news from ESMO 2021: results from the most important clinical studies22/09/2021
CDK7 inhibition, a new strategy discussed during ESMO27/09/2021
Promising approaches with de-escalation and new adjuvant therapy combinations; insights into ‘ideal’ adjuvant therapy for post-menopausal patients and new SERDs (in advanced breast cancer too)
Many studies focused on early stage breast cancer were discussed during the last ESMO congress, showing many relevant results. Three studies were discussed to evaluate de-escalation in HER2- early stage breast cancer. Two metanalysis pointed out the feasibility of this approach, showing that six-month treatment with the anti-HER2 antibody, trastuzumab, was non- inferior to twelve-month treatment, while a third analysis evaluated the predictive impact of biomarkers on outcomes after de-escalation of neoadjuvant treatment in patients with HER2-positive, hormone receptor-negative early breast cancer. To define which patients can be de-escalated without compromising their prognosis there’s the need to identify biomarkers: that’s why future research should include molecular imaging or circulating tumor DNA monitoring to gain a better understanding of the disease process.
Data from a study of Gruppo Italiano Mammella are relevant too: the trial, aimed to evaluate optimal duration of letrozole adjuvant therapy (2-3 years vs 5 years), recruited almost 2000 post-menopausal patients with stage I/III breast cancer free of recurrence after 2-3 years of tamoxifen. Results show a significant benefit in disease free survival, 62% and 67% in the control (2-3 y) and extended arm (5 y), respectively; positive results were seen on overall survival too (84% in the control arm and 88% in the 5 year arm): an overall endocrine adjuvant treatment of 7-8 years should therefore be considered an optimal duration. Moreover, in patients with previously untreated stage II/III triple negative breast cancer, the phase III BrighTNess trial showed an improvement in event-free survival by adding carboplatin to paclitaxel in a neoadjuvant setting, whereas incorporating a third drug, veliparib, doesn’t confer additional benefits. Clinical results were obtained regardless of BRCA status and without an increase in hematologic adverse events, such as myelodysplastic syndrome or acute myeloid leukemia.
CoopERA phase II trial interim analysis featured interesting data in ER+/HER2- early stage breast cancer: a neoadjuvant therapy with palbociclib and giredestrant, a novel Selective Estrogen Receptor Degrader (SERD), demonstrated superior antiproliferative activity compared to anastrozole, as showed by the relative Ki67 proliferation index reduction. Giredestrant, that received FDA Fast Track Designation for second and third line metastatic breast cancer on 15 December 2020, is not the only novel SERD with promising activity: a subgroup analysis of the phase I/II AMEERA-1 study on metastatic breast cancer reported that amcenestrant plus palbociclib led to an objective response rate of 32.4%. Novel SERD, almost 10 different molecules in different stages of clinical development, could become very useful because they provide more convenient dosing than fulvestrant (thanks to oral vs intramuscular administration) and they showed good activity and tolerability in both early and advanced settings.