Daily highlight in metastatic breast cancer

Reported by Dr Kevin Punie  – GZA Hospital Sint Augustinus, Wilrijk, Belgium

During the session, updated findings from the BEGONIA trial were unveiled, centering on an investigation into the effectiveness of a novel TROP2-directed Antibody Drug Conjugate (ADC) named datopotamab deruxtecan (Dato-DXd) in combination with the immune checkpoint inhibitor durvalumab (D) for patients with advanced triple-negative breast cancer. Despite being a single-arm study with preliminary data, the results are promising, revealing an exceptionally high objective response rate of nearly 80%. Notably, 80% of the 60 patients studied lacked PD-L1 expression, a group typically considered unresponsive to checkpoint inhibitors. Thus, it is intriguing to explore the option of administering a more potent therapeutic component in their treatment regimen, beyond conventional backbone chemotherapy, especially if deemed safe in terms of pulmonary toxicity.

Additionally, the session featured updated efficacy data from the TULIP trial, primarily focusing on overall survival (OS). This phase 3 trial compared the use of a novel anti-HER2 targeted ADC, trastuzumab duocarmazine, against physician’s choice therapy. Earlier results had shown a modest yet statistically significant positive impact on Progression-Free Survival (PFS), albeit with an unfavourable toxicity profile. The updated OS analysis, however, indicated no significant improvement, posing a significant challenge for a drug burdened with such adverse side effects. This situation could impede its acceptance into clinical practice.

Furthermore, the FALCON study, a longstanding phase 3 trial, investigated fulvestrant versus anastrozole as first-line endocrine therapy for patients with advanced ER(+) HER2(-) breast cancer. It is crucial to note that this patient subset represents a minority of the population. Previous data had suggested improved PFS, albeit only in patients with non-visceral disease. The final analysis on OS revealed no superiority of fulvestrant over anastrozole. The same pattern persisted when examining specific subgroups, indicating a consistent outcome: fulvestrant showed improvement compared to anastrozole. However, the clinical implications of this study are likely to be limited.

References:

Peter Schmid  – Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): updated results from BEGONIA, a phase 1b/2 study – ESMO 2023 – 379MO

Philippe Aftimos – Trastuzumab duocarmazine versus physician’s choice therapy in pre-treated HER2-positive metastatic breast cancer: final results of the phase III TULIP trial – ESMO 2023 – 386MO

John Robertson – Final overall survival analysis for fulvestrant vs anastrozole in endocrine therapy (ET)-naïve, hormone receptor-positive (HR+) advanced breast cancer (FALCON) – ESMO 2023 – 384MO