Evaluation of Hypertension and Proteinuria as Markers of Efficacy in Antiangiogenic Therapy for Metastatic Colorectal Cancer

Khoja, Leila; Kumaran, G.; Zee, Ying Kiat; Murukesh, Nishanth; Swindell, Ric; Saunders, Mark; Clamp, Andrew R.; Valle, Juan W; Wilson, Gregory; Jayson, Gordon C; Hasan, Jurjees

doi:10.1097/mcg.0b013e3182a8804c

Cited by 27 publications

(22 citation statements)

References 22 publications

(24 reference statements)

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“…Finally, sorafenib‐induced hypertension predicted a better outcome of cancer patients. This should not come as a surprise, as numerous reports (only few cited here) have shown a similar finding in antiangiogenic cancer therapy . As a matter of fact, when different VPIs were compared head‐to‐head, the ones with more frequent hypertension also had longer progression‐free survival .…”

supporting

confidence: 76%

Lessons from Antiangiogenic Cancer Therapy–Induced Hypertension

Bursztyn

2014

J of Clinical Hypertension

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supporting

confidence: 76%

Lessons from Antiangiogenic Cancer Therapy–Induced Hypertension

Bursztyn

2014

J of Clinical Hypertension

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“…Our study shows a strong correlation between the development of hypertension and treatment efficacy, with a 2.7‐fold reduction in the risk of progression. This development of an anti‐VEGF class toxicity as an efficacy marker has been reported with other anti‐angiogenic drugs . Retrospective studies have reported an association between the development of grade 2/3 hypertension with bevacizumab in first‐line treatment of colon cancer in terms of response rate and PFS .…”

Section: Discussionmentioning

confidence: 63%

Efficacy and safety of FOLFIRI/aflibercept in second‐line treatment of metastatic colorectal cancer in a real‐world population: Prognostic and predictive markers

et al. 2019

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Purpose The phase III VELOUR trial demonstrated efficacy with combined FOLFIRI‐aflibercept in patients with metastatic colorectal cancer previously treated with oxaliplatin with or without bevacizumab versus placebo. The effect of FOLFIRI‐aflibercept in routine clinical practice was evaluated. Methods/Patients Overall survival (OS), progression‐free survival (PFS), response and safety were analysed for 78 patients treated with FOLFIRI‐aflibercept at six GITuD institutions. Exploratory analyses of prognostic and predictive markers of efficacy were performed. Results Patients had good general status (PS 0‐1 96.2%), tumours were mostly RAS‐mutant (75.6%), synchronous (71.8%), and left‐sided (71.8%). Prior therapy included bevacizumab (47.4%) and anti‐EGFR agents (12.8%). PFS was longer for metachronous than synchronous tumours (11.0 vs 5.0 months, P = 0.028), and for left‐colon tumours (7.0 vs 3.0 months, P = 0.044). RAS‐mutant status, first‐line treatment and primary tumour surgery did not impact PFS. The disease control rate was 70.5%. The most common grade 3/4 toxicities were neutropenia (15.3%), asthenia (10.3%), diarrhea and mucositis (6.4% each). Dysphonia was reported in 39.7% of patients, and grade 3 hypertension in 3.8%. Development of hypertension (any grade) was significantly associated with a reduced risk of progression by multivariate analysis (HR = 2.7; 95%CI 1.3‐5.4; P = 0.001). Conclusions Efficacy with FOLFIRI‐aflibercept in a real‐life population was in line with results from the pivotal trial and toxicity was manageable with treatment adaptation. Survival outcomes were not impacted by primary tumour location, RAS‐mutant status, first‐line treatment or primary tumour surgery. Hypertension may be a surrogate marker of efficacy in this patient population.

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“…VEGF pathway). This concept is further supported by evidence that bevacizumab, a monoclonal anti-VEGF-A antibody, and aflibercept, a soluble receptor with affinity to VEGF-A and -B, are also strong inducers of hypertension [20,21]. Inhibition of the VEGF pathway induces hypertension as a class effect; VEGFR-2 is most prominent of those [22][23][24].…”

Section: Pathogenesis Of Hypertension Secondary To Vsp Inhibitionmentioning

confidence: 51%

Hypertension in cancer patients treated with anti-angiogenic based regimens

et al. 2015

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New anti-cancer drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway are highly effective in the treatment of solid tumors, however concerns remain regarding their cardiovascular safety. The most common side effect of VEGF signaling pathway (VSP) inhibition is the development of systemic hypertension. We review the incidence, possible mechanisms, significance and management of hypertension in patients treated with VSP inhibitors.

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Evaluation of Hypertension and Proteinuria as Markers of Efficacy in Antiangiogenic Therapy for Metastatic Colorectal Cancer

Cited by 27 publications

References 22 publications

Lessons from Antiangiogenic Cancer Therapy–Induced Hypertension

Lessons from Antiangiogenic Cancer Therapy–Induced Hypertension

Efficacy and safety of FOLFIRI/aflibercept in second‐line treatment of metastatic colorectal cancer in a real‐world population: Prognostic and predictive markers

Hypertension in cancer patients treated with anti-angiogenic based regimens

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