RESUMO
: Background: The optimal anti-angiogenic strategy as second-line treatment in RAS wild-type metastatic colorectal cancer (mCRC) treated with anti-EGFR (Epidermal Growth Factor Receptor) based first-line treatment is still debated. METHODS: This multicenter, real-world, retrospective study is aimed at evaluating the effectiveness of second-line Bevacizumab- and Aflibercept-based treatments after an anti-EGFR based first-line regimen. Clinical outcomes measured were: objective response rate (ORR), progression free survival (PFS), overall survival (OS) and adverse events (AEs) profiles. RESULTS: From February 2011 to October 2019, 277 consecutive mCRC patients received Bevacizumab-based (228, 82.3%) or Aflibercept-based (49, 17.7%) regimen. No significant difference was found regarding ORR. The median follow-up was 27.7 months (95%CI: 24.7-34.4). Aflibercept-treated group had a significantly shorter PFS compared to Bevacizumab-treated group (5.6 vs. 7.1 months, respectively) (HR = 1.34 (95%CI: 0.95-1.89); p = 0.0932). The median OS of the Bevacizumab-treated group and Aflibercept-treated group was 16.2 (95%CI: 15.3-18.1) and 12.7 (95%CI: 8.8-17.5) months, respectively (HR= 1.31 (95%CI: 0.89-1.93) p = 0.16). After adjusting for the key covariates (age, gender, performance status, number of metastatic sites and primary tumor side) Bevacizumab-based regimens revealed to be significantly related with a prolonged PFS (HR = 1.44 (95%CI: 1.02-2.03); p = 0.0399) compared to Aflibercept-based regimens, but not with a prolonged OS (HR = 1.47 (95%CI: 0.99-2.17); p = 0.0503). The incidence of G3/G4 VEGF inhibitors class-specific AEs was 7.5% and 26.5% in the Bevacizumab-treated group and the Aflibercept-treated group, respectively (p = 0.0001). CONCLUSION: Our analysis seems to reveal that Bevacizumab-based regimens have a slightly better PFS and class-specific AEs profile compared to Aflibercept-based regimen as second-line treatment of RAS wild-type mCRC patients previously treated with anti-EGFR based treatments. These results have to be taken with caution and no conclusive considerations are allowed.
RESUMO
BACKGROUND: Besides its role as oxygen transporter, recent findings suggest that haemoglobin beta (HBB) may have roles in other contexts. METHODS: We evaluated the impact of HBB expression in primary human breast cancers, and in breast cancer cell lines overexpressing HBB by in vitro and in vivo studies. Publicly available microarray databases were used to perform multivariate survival analyses. RESULTS: A significantly higher expression of HBB was observed in invasive carcinoma histotypes vs in situ counterparts, along with a positive correlation between HBB and the Ki67 proliferation marker. HBB-overexpressing breast cancer cells migrate and invade more, show HIF-1α upregulation and their conditioned media enhances angiogenesis. Blocking the oxygen-binding site of HBB reverts the increase of migration and HIF-1α upregulation observed in HBB-overexpressing breast cancer cells. Orthotopically implanted MDA-MB-231 overexpressing HBB (MDA-HBB) generated tumours with faster growth rate and increased neoangiogenesis. Moreover, local recurrence and visceral metastases were observed only in MDA-HBB-implanted mice. Similar results were observed with 4T1 mouse breast cancer cells. Finally, bioinformatics analyses of public data sets correlated high HBB expression with lower overall survival. CONCLUSIONS: HBB expression increases breast cancer cells aggressiveness and associates with poor prognosis, pointing to HBB as a novel biomarker for breast cancer progression.