Highlight 5

Dr Glenn Vergauwen, an oncological gynaecologist at the University Hospital Ghent, reported on the first rapid-fire session at this SABCS 2023. 

The first presentation by Dr Vergauwen is the SERENA-3 trial, a preoperative window of opportunity trial focusing on the biological impacts of camizestrant, a novel oral SERD. The trial sought to examine the biological effects on the estrogen receptor and Ki67 in patients. Various dosages of camizestrant—75 milligrams, 150 milligrams, and 300 milligrams—were administered, with the primary objective of assessing the reduction in the estrogen receptor. The findings, revealed a significant reduction in the estrogen receptor independent of dosage or treatment duration. Furthermore, concerning secondary endpoints, a notable decrease in Ki67 was observed after 12 to 15 days, irrespective of the dosage administered. When considered alongside the Serena 2 trial, previously published, this study suggests that, for forthcoming research, the optimal camizestrant dosage for these patients would be 75 milligrams.

The second trial in this daily highlight is a study focusing on endoxifen. In the context of a preventive strategy, the trial aimed to assess the dermal safety and tolerability of locally administered endoxifen on the skin of the breast. Endoxifen, a potent metabolite of tamoxifen, exhibits notably enhanced anti-estrogenic activity. The study reported favourable dermal tolerability, with no major concerns arising regarding skin reactions. To further ensure safety, blood samples were analysed, revealing minimal exposure of endoxifen in the systemic circulation. Additionally, examination of tissue samples showcased a uniform and homogeneous distribution of endoxifen in the breast tissue. This investigation introduces a novel potential strategy in the preventive setting of breast cancer through the localised administration of endoxifen.

The next interesting study is the FOENIX-MBC2 trial, which centers on the utilization of futibatinib, an FGFR1 inhibitor. FGFR1 amplification is identified in approximately 10% of all invasive breast cancer tumours. The primary aim of this study was to investigate the anti-tumour activity of futibatinib in patients with FGFR amplification. Futibatinib was administered as monotherapy or in combination with fulvestrant. The trial focused on a pretreated population with an average of three prior lines of systemic treatment, all of whom had previously undergone CDK4/6 inhibitor therapy. The primary endpoint of the study was PFS at six months, and notably, nearly 50% of the patients exhibited PFS at this milestone. These outcomes, particularly when compared to the use of fulvestrant in post-CDK4/6 patients, present highly promising results. The study suggests that futibatinib, either alone or in combination with fulvestrant, holds potential as an effective treatment for patients with FGFR1-amplified invasive breast cancer, particularly in those with prior CDK4/6 inhibitor exposure.

The final study reported of this session is an investigation into tinengotinib, a novel multi-kinase inhibitor. This trial focused on patients with advanced metastatic breast cancer, encompassing those with HR+/HER2- and triple-negative tumours. Tinengotinib, acting as a multi-kinase inhibitor, was administered either as monotherapy or in combination with Nab-paclitaxel.  Significantly, this was a heavily pre-treated population with a mean of five prior systemic lines in metastatic setting. The treatment exhibited favourable tolerability, with hypertension, stomatitis, and hand-foot syndrome being the most commonly observed side effects. In terms of outcomes, the objective response rate reached up to 50% in the HR+ group and approximately 25% in the triple-negative group. Regarding PFS, the HR+ group demonstrated a median PFS of 5.5 months, while the triple-negative group exhibited a median PFS of 2.7 months. These findings present highly promising results, warranting further research into the potential of tinengotinib as a therapeutic option for advanced metastatic breast cancer, particularly in heavily pre-treated populations.

References:

Robertson J. et al., SERENA-3: A randomized pre-surgical window of opportunity study assessing dose and duration of camizestrant treatment in post-menopausal women with ER-positive, HER2-negative primary breast cancer – SABCS 2023, #RF01-01

Lee O. et al., A randomized Phase I pre-operative window trial of transdermal endoxifen in women planning mastectomy: evaluation of dermal safety, intra-mammary drug distribution, and biologic effects – SABCS 2023, #RF01-01

Damodaran S., Final results from the phase 2, open-label FOENIX-MBC2 study: efficacy and safety of futibatinib in adult patients with locally advanced/metastatic HR+/HER2− breast cancer harboring high-level FGFR1 gene amplification – SABCS 2023, #RF01-04

Sarina P-P. et al., The efficacy and safety of tinengotinib in patients with advanced or metastatic HR+/HER2- breast cancer or TNBC – SABCS 2023, #RF01-07