Monoclonal antibodies for the treatment of non-haematological tumours: update of an expanding scenario

Bronte, Giuseppe; Sortino, Giuseppe; Passiglia, Francesco; Rizzo, Sérgio; Vullo, Francesca Lo; Galvano, Antonio; Bazan, Viviana; Rolfo, Christian

doi:10.1517/14712598.2015.963052

Cited by 9 publications

(6 citation statements)

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“…Cancer immunotherapy is emerging as a very promising therapeutic strategy for several solid tumors, including non-small cell lung cancer (NSCLC). Differently from other treatment approaches directed against the tumor, such as chemotherapy or targeted therapy [ 1 - 6 ], targeting the immune system offers the potential for durable activity and long-term survival outcomes, regardless of tumor's histological subtype or mutation status, with a unique, tolerable, toxicity profile. Among the different immunotherapeutic strategies under clinical investigation in NSCLC, the blockade of inhibitory immune-checkpoints with monoclonal antibodies (MoAbs), is currently considered the most promising approach, promoting the immune-response against cancer cells [ 7 - 9 ].…”

Section: Introductionmentioning

confidence: 99%

PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis

et al. 2016

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BackgroundClinical trials of immune checkpoints modulators, including both programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, have recently shown promising activity and tolerable toxicity in pre-treated NSCLC patients. However the predictive role of PD-L1 expression is still controversial. This pooled analysis aims to clarify the association of clinical objective responses to anti PD-1/PD-L1 monoclonal antibodies (MoAbs) and tumor PD-L1 expression in pre-treated NSCLC patients.MethodsData from published studies, that evaluated efficacy and safety of PD-1/PD-L1 inhibitors in pre-treated NSCLC patients, stratified by tumor PD-L1 expression status (immunohistochemistry, cut-off point 1%), were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference of Lung Cancer, meeting proceedings. Pooled Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated for the Overall Response Rate (ORR) (as evaluated by Response Evaluation Criteria in Solid Tumors, version 1.1), according to PD-L1 expression status.ResultsA total of seven studies, with 914 patients, were eligible. Pooled analysis showed that patients with PD-L1 positive tumors (PD-L1 tumor cell staining ≥1%), had a significantly higher ORR, compared to patients with PD-L1 negative tumors (OR: 2.44; 95% CIs: 1.61-3.68).ConclusionsPD-L1 tumor over-expression seems to be associated with higher clinical activity of anti PD-1/PD-L1 MoAbs, in pre-treated NSCLC patients, suggesting a potential role of PD-L1 expression, IHC cut-off point 1%, as predictive biomarker for the selection of patients to treat with immune-checkpoint inhibitors.

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Section: Introductionmentioning

confidence: 99%

PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis

et al. 2016

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“…Resection of the CLM, sometimes in combination with other local treatment modalities, such as radiofrequency ablation (RFA), has become the standard of care, and offers the only potential for cure (Chiappa et al, 2009;Ksienski et al, 2010). The development of new surgical approaches, together with an increasing use of the perioperative systemic therapy, have led to an increase of the percentage of patients potentially eligible for curative liver resection (Rolfo et al, , 2013Bronte et al, 2015Bronte et al, , 2013. In most series, up to 25% of patients presenting with stage IV CRC undergo hepatic resection (Kopetz et al, 2009), with reported 5-year survival rates up to 50% (Taylor et al, 2010;Choti et al, 2002;Chua et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Can KRAS and BRAF mutations limit the benefit of liver resection in metastatic colorectal cancer patients? A systematic review and meta-analysis

Passiglia

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Bazan

et al. 2016

Critical Reviews in Oncology/Hematology

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Background: Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of CRC-related liver metastases (CLM), showing conflicting results. This meta-analysis aims to review all the studies reporting survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients undergoing resection of CLM, stratified according to KRAS and/or BRAF mutation status. Materials and methods: Data from all published studies reporting survival outcomes (RFS and/or OS) of CRC patients who received resection of CLM, stratified by KRAS and/or BRAF mutation status were collected, according to the PRISMA guidelines. Pooled HRs were calculated for both the OS and/or RFS. Results: Seven eligible trials (1403 patients) were included. Pooled analysis showed that KRAS mutations predicted a significantly worse both RFS (HR: 1.65; 95% CI: 1.23-2.21) and OS (HR: 1.86; 95% CI: 1.51-2.30) in patients who underwent surgical resection of CLM. BRAF mutations were also associated with a significantly worse OS (HR: 3.90; 95% CI: 1.96-7.73) in this subgroup of patients. Conclusions: This meta-analysis suggests both KRAS and BRAF mutations as poor, prognostic biomarkers, associated with worse survival outcomes, in patients undergoing hepatic resection of CLM

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“…Based on these known signaling pathways, targeted systemic treatments have been specifically designed and approved: the humanized anti-VEGF monoclonal antibody bevacizumab [13, 14] in combination with IFN-α, four multitargeted tyrosine kinase inhibitors (TKIs): sorafenib, sunitinib, pazopanib and axitinib; and two kinase inhibitors of mTOR, temsirolimus and everolimus (Figure 1). …”

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confidence: 99%

Beyond evidence-based data: scientific rationale and tumor behavior to drive sequential and personalized therapeutic strategies for the treatment of metastatic renal cell carcinoma

et al. 2016

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The recent advances in identification of the molecular mechanisms related to tumorigenesis and angiogenesis, along with the understanding of molecular alterations involved in renal cell carcinoma (RCC) pathogenesis, has allowed the development of several new drugs which have revolutionized the treatment of metastatic renal cell carcinoma (mRCC).This process has resulted in clinically significant improvements in median overall survival and an increasing number of patients undergoes two or even three lines of therapy. Therefore, it is necessary a long-term perspective of the treatment: planning a sequential and personalized therapeutic strategy to improve clinical outcome, the potential to achieve long-term response, and to preserve quality of life (QOL), minimizing treatment-related toxicity and transforming mRCC into a chronically treatable condition.Because of the challenges still encountered to draw an optimal therapeutic sequence, the main focus of this article will be to propose the optimal sequencing of existing, approved, oral targeted agents for the treatment of mRCC using evidence-based data along with the knowledge available on the tumor behavior and mechanisms of resistance to anti-angiogenic treatment to provide complementary information and to help the clinicians to maximize the effectiveness of targeted agents in the treatment of mRCC.

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Monoclonal antibodies for the treatment of non-haematological tumours: update of an expanding scenario

Abstract: (2015) Monoclonal antibodies for the treatment of non-haematological tumours: update of an expanding scenario, Expert Opinion on Biological Therapy, 15:1, 45-59,

Cited by 9 publications

References 116 publications

PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis

PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis

Can KRAS and BRAF mutations limit the benefit of liver resection in metastatic colorectal cancer patients? A systematic review and meta-analysis

Beyond evidence-based data: scientific rationale and tumor behavior to drive sequential and personalized therapeutic strategies for the treatment of metastatic renal cell carcinoma

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