Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer

Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan.

Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for ‘sacituzumab govitecan’ and ‘clinical trial’.

Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.     

Can EGFR mutation status be reliably determined in pre‐operative needle biopsies from adenocarcinomas of the lung?

The identification of EGFR mutations in non‐small‐cell lung cancer is important for selecting patients, who may benefit from treatment with EGFR tyrosine kinase inhibitors. The analysis is usually performed on cytological aspirates and/or histological needle biopsies, representing a small fraction of the tumour volume. The aim of the present investigation was to evaluate the diagnostic performance of this molecular test. We retrospectively included 201 patients with primary adenocarcinoma of the lung. EGFR mutation status (exon 19 deletions and exon 21 L858R point mutation) was evaluated on both pre‐operative biopsies (131 histological and 70 cytological) and on the surgical specimens, using PCR. Samples with low tumour cell fraction were assigned to laser micro‐dissection (LMD). We found nine (4.5%) patients with EGFR mutation in the lung tumour resections, but failed to identify mutation in one of the corresponding pre‐operative, cytological specimens. Several (18.4%) analyses of the pre‐operative biopsies were inconclusive, especially in case of biopsies undergoing LMD and regarding exon 21 analysis. Discrepancy of mutation status in one patient may reflect intra‐tumoural heterogeneity or technical issues. Moreover, several inconclusive results in the diagnostic biopsies reveal that attention must be paid on the suitability of pre‐operative biopsies for EGFR mutation analysis.     

Light absorbing properties of indocyanine green (ICG) in solution and after adsorption to the retinal surface — an ex-vivo approach

BACKGROUND: To evaluate potential differences in light absorbing properties and stability of indocyanine green (ICG) adsorbed to the retinal surface and of ICG dissolved in water and balanced salt solution. METHODS: The retina of four human donor eyes was prepared by removing the vitreous from the retinal surface. The inner surface of the specimen was covered with two to three drops of a 0.05% or 0.15% ICG solution respectively. After 1 min, the dye was removed by careful irrigation using BSS plus. The retinal specimens were then investigated by diffuse reflection spectroscopy (UV/VIS/NIR Spectrometer Lambda 900/Perkin Elmer equipped with a PELA-1020 integrating sphere accessory) and their absorption evaluated by the Kubelka-Munk function. To control the sensitivity of the setting, diffuse reflectance spectra of ICG adsorbed to a cellulose membrane and Al(2)O(3) were measured. For comparison, absorption spectra of ICG dissolved in water and BSS plus solution were measured in relation to ICG concentration and time using an UV/VIS/NIR Spectrometer Lambda 900/Perkin Elmer. RESULTS: On the retinal surface, absorption spectra exhibited a steep increase of absorption beginning at 620 nm, with a maximum at 736 nm (0.05%) and a shoulder at 745 (0.15%) and a second maximum at approximately 800 nm for both concentrations. Repeated measurement of the retinal surface 13 days after the ICG exposure revealed no changes in the position of the maxima as compared to the initial measurements. Light absorbing properties of ICG on cellulose or Al(2)O(3) are similar to those seen on the retinal surface with respect to the pattern and location of absorption maxima. In contrast, ICG dissolved in water or BSS plus disclosed variations in absorption characteristics depending on dye concentration, solute and time of measurement. CONCLUSIONS: Absorption characteristics and stability of ICG bound to the retinal surface could be of relevance when investigating potential pathomechanisms of ICG related toxicity, which might be related not only to intraoperative but also to postoperative light exposure of patients after intravitreal use of ICG.