Purpose
Bevacizumab, a humanized, anti-vascular endothelial growth factor-A monoclonal antibody, has shown efficacy in a number of cancers. However, its use in metastatic breast cancer (MBC) remains ...controversial.
Methods
A literature review using the PubMed database was performed to update the currently available clinical trials evidence on bevacizumab in the first-line treatment of breast cancer. In addition, the proceedings of selected oncology annual meetings were searched for relevant presentations.
Results
This article reviews the available evidence for bevacizumab as first-line therapy for MBC and discusses its current and future applicability in the management of MBC. Three phase III trials (ECOG-2100, AVADO, RIBBON-1) demonstrated that the addition of bevacizumab to chemotherapy is well-tolerated and improves progression-free survival and objective response rates in the first-line setting. These findings were supported by a large clinical practice-based study (ATHENA) and a recent clinical trial in which bevacizumab added to paclitaxel showed notable activity in triple-negative MBC. However, bevacizumab has thus far not demonstrated a significant benefit in overall survival.
Conclusions
The addition of bevacizumab to chemotherapy is well-tolerated and produces substantial improvements in overall response rate and progression-free survival, compared with chemotherapy alone, in advanced HER2-negative breast cancer. Nevertheless, it has thus far not demonstrated a significant benefit in overall survival. Whether prolongation of progression-free survival is enough to consider bevacizumab efficacious is unclear. Based on the available clinical trials results, bevacizumab is a part of the complex therapeutic strategy of advanced HER2-negative breast cancer.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
The prognostic value associated with the detection of circulating tumor cells (CTCs) in metastatic breast cancer by the CellSearch™ technology raise additional issues regarding the biological value ...of this information. We postulated that a drug‐resistance profile of CTCs may predict response to chemotherapy in cancer patients and therefore could be used for patient selection. One hundred 5 patients with diagnosis of carcinoma were enrolled in a prospective trial. CTCs were isolated from peripheral blood, and positive samples were evaluated for the expression of a panel of genes involved in anticancer drugs resistance. The drug‐resistance profile was correlated with disease‐free survival (DFS; patients in adjuvant setting) and time to progression (TTP; metastatic patients) in a 24‐months follow‐up. Objective response correlation was a secondary end point. Fifty‐one percent of patients were found positive for CTCs while all blood samples from healthy donors were negative. The drug‐resistance profile correlates with DFS and TTP (p < 0.001 in both). Sensitivity of the test: able to predict treatment response in 98% of patients. Specificity of the test: 100%; no sample from healthy subject was positive for the presence of CTCs. Positive and negative predictive values were found to be 96.5 and 100%, respectively. We identified a drug‐resistance profile of CTCs, which is predictive of response to chemotherapy, independent of tumor type and stage of disease. This approach may represent a first step toward the individualization of chemotherapy in cancer patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Background: Up to 6% of patients (pts) with HER2 positive (pos) metastatic breast cancer (MBC) experience a radiologic complete response (rCR) to a first line of therapy, but these results ...mostly derive from dated and/or limited cohorts. Aim of this study was to define the clinico-pathological characteristics of HER2 positive (pos) MBC pts experiencing a rCR. Methods: Pts were selected from the database of the GIM14 study (NCT02284581) and classified according to the best radiologic response obtained to the first line chemotherapy (CT) and upon time-to-treatment-failure (TTF). rCR was defined as complete response (CR) with a TTF > 3 months. The association across variables was tested through logistic regression and their prognostic impact in terms of overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Results: Of the 3,423 pts included in the GIM14 study, 814 had HER2 pos MBC. After exclusion of pts treated with first line endocrine therapy and/or with TTF < 3 months, 656 pts were included in the present analysis, of which 96 (14.6%) experienced a rCR. Instead, the best response was a partial response for 295 pts (45.0%), stable disease for 221 pts (33.7%), and progression for 44 pts (6.7%). Most pts (59.8%) presented de novo MBC; 379 pts (57.8%) had visceral metastases (mets), 609 pts (92.8%) did not have central nervous system (CNS) involvement and 318 pts (48.5%) had only 1 site of distant mets. Also, 445 pts (67.9%) had hormone receptor (HR) pos disease, a HER2 3+ score at immunohistochemistry (IHC) was present in 59.8% of cases versus 40.2% with HER2 2+ at IHC and in situ hybridization (ISH) + disease. Taxanes were the main CT backbone (489 pts, 74.5%), 341 pts (52.0%) had received a Trastuzumab-Pertuzumab doublet. At multivariable analysis, higher odds of experiencing a rCR were reported for presence of non-visceral mets (OR 1.87, 95%CI 1.10-3.17), low number of metastatic sites (OR 2.42, 95%CI 0.80-7.33 for 1 site only) and HER2 3+ score at IHC (OR 1.80, 95%CI 1.09-2.98). Disease-free interval (DFI) was associated to rCR at univariable but not at multivariable analysis. HR status, CT backbone and type of anti-HER2 regimen were not associated with rCR neither at univariable nor at multivariable analysis. Median follow-up was 76.2 months. Amongst pts with TTF>12 months, those with rCR had a significantly higher OS compared to those not experiencing a rCR (median OS 133 and 90 months, respectively; p=0.0191). OS rates in pts with TTF ≥ 12 months were 97.8% at 2-year follow-up and 59.4% at 5-year follow-up. Instead, in pts with TTF ≥ 60 months, OS rates were 76.7% at 10-year follow-up. Amongst the 96 pts experiencing a CR, 38 had a rCR with TTF between 12 and 60 months, while 22 pts had a rCR with a TTF ≥ 60 months. The remaining pts had a CR with a TTF < 12 months. Pts with HR negative (neg) disease were found to be more likely to experience a rCR with a with TTF between 12 and 60 months, whilst pts with HR pos disease had a higher probability to experience a rCR with a TTF ≥ 60 months (p=0.0074). Pts with HER2 3+ score at IHC had a higher probability to achieve a rCR with a TTF ≥ 12 months compared to pts with HER2 2+ score at IHC and ISH + (p=0.0216). Age at diagnosis, menopausal status, DFI, number and site of mets, CT backbone and anti-HER2 therapy did not influence the duration of the rCR obtained. Conclusions: This study characterized a real-world cohort of HER2 positive MBC patients experiencing radiologic complete response to a first line treatment. Based on these results a clinical trial focused on liquid biopsy-based minimal residual disease is being designed. Novel anti-HER2 agents are gaining momentum as ever increasingly effective treatments and future de-escalation strategies after complete response will represent a growing need.
Citation Format: Linda Cucciniello, Eva Blondeaux, Claudia Bighin, Simona Gasparro, Stefania Russo, Arianna Dri, Palma Pugliese, Andrea Fontana, Giuseppe Naso, Antonella Ferzi, Ferdinando Riccardi, Valentina Sini, Luca Boni, Alessandra Fabi, Filippo Montemurro, Michelino De Laurentiis, Grazia Arpino, Lucia Del Mastro, Lorenzo Gerratana, Fabio Puglisi. Assessing the clinico-pathological characteristics of HER2 positive metastatic breast cancer patients experiencing radiologic complete response in a nationwide cohort abstract. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-04.
Issue Title: Special Issue: Performance Based Design in Earthquake Geotechnical Engineering | Seismic microzonation of Palatine hill, Roman Forum and Coliseum Archaeological Area
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
An approach devoted to quickly assess the thickness of soft sedimentary cover in areas of unknown subsurface morphology is applied in this study. In particular, soil thickness (h) is derived by ...combining estimates of the resonance frequency (f
r
) relative to soft sediments with the local shear-wave velocity (V
s
) profile. For this purpose, (f
r
) values are assessed from horizontal to vertical (H/V) spectral ratios of seismic noise recordings and the (V
s
) profile is obtained by considering information from shallow seismic surveys. Results obtained for a Quaternary sedimentary basin in Southern Italy are discussed. Since in the investigated area only weak independent constraints are available, special emphasis is given to the assessment of uncertainties involved in this estimate of soil thickness.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Resistance to anthracyclines is responsible for treatment failure in most patients with metastatic breast cancer. According to recent studies, the expression of specific drug transporters (MRPs) on ...circulating tumor cells is predictive of prognosis in different cancer types. We observed that patients whose circulating tumor cells expressed MRP1 and MRP2, two drug-export pumps responsible for anthracyclines efflux, who received conventional anthracyclines had a significantly shorter time to progression compared with patients sharing same characteristics who received non pegylated liposomal doxorubicin (P < 0.005). These results may highlight a new appealing role of the liposomal doxorubicin formulation, not only because of its reduced cardiac toxicity but especially referring to its theoretical efficacy in anthracycline-resistant breast cancer patients.
This paper focuses on the boundary area between the Central and Southern Apennines thrust belt of the Italian peninsula, which separates two different patterns of distribution of active faults and ...strong earthquakes along the Apennines chain. In order to reduce the remarkable lack of data on this area, part of this boundary has been investigated. The study area corresponds to the surroundings of the town of Isernia, an important centre of the Molise region, and contains the Carpino and Le Piane (CLP) intermountain Basins of Quaternary age. The research was based on unpublished data, consisting of 65 well logs drilled in the CLP Basins, integrated with detailed field surveys (scale 1:10,000), mesoscale structural analysis and aerial photograph interpretation. This study allowed to define the geometry and kinematics of the CLP Basins. They result to be asymmetric half-grabens partially filled with fluvio-lacustrine deposits, where the sedimentation is controlled by the activity of a set of normal faults striking N30°W and NE dipping. This set of faults, which developed mainly during the Late Pleistocene–Holocene, is about 10 km long and is located close to the northwestern end of the Boiano Basin extensional Fault System. The average slip rate calculated for part of the Holocene for one of the recognised faults ranges from 0.75 to 1.00 mm/year. The identification of the active CLP Basins Fault System partially fills the gap of data at the boundary between the Central and Southern Apennines. From a more general point of view, we hypothesise that this boundary might be regarded as a “persistent segment boundary”, forming a long-term barrier to the propagation of rupture of active fault systems. Under this perspective, a redefinition of the seismic zonation of Italy for the study area is suggested.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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