Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases

Abstract

Efaproxiral (Efaproxynt, RSR13), a synthetic allosteric modifier of haemoglobin (Hb), decreases Hb-oxygen (O 2 ) binding affinity and enhances oxygenation of hypoxic tumours during radiation therapy. This analysis evaluated the Phase 3, Radiation Enhancing Allosteric Compound for Hypoxic Brain Metastases; RT-009 (REACH) study efficacy results in relation to efaproxiral exposure (efaproxiral red blood cell concentration (E-RBC) and number of doses). Recursive partitioning analysis Class I or II patients with brain metastases from solid tumours received standard whole-brain radiation therapy (3 Gy/fraction  10 days), plus supplemental O 2 (4 l/min), either with efaproxiral (75 or 100 mg/kg daily) or without (control). Efaproxiral red blood cell concentrations were linearly extrapolated to all efaproxiral doses received. Three patient populations were analysed: (1) all eligible, (2) non-small-cell lung cancer (NSCLC) as primary cancer, and (3) breast cancer primary. Efficacy endpoints were survival and response rate. Brain metastases patients achieving sufficient E-RBC (X483 mg/ml) and receiving at least seven of 10 efaproxiral doses were most likely to experience survival and response benefits. Patients with breast cancer primary tumours generally achieved the target efaproxiral exposure and therefore gained greater benefit from efaproxiral treatment than NSCLC patients. This analysis defined the efaproxiral concentration-dependence in survival and response rate improvement, and provided a clearer understanding of efaproxiral dosing requirements.

Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy

“…In addition, a clinical study has shown that acetyl-CoA metabolism is important with high level of acetyl-CoA oxidase 1 in BM from breast cancer in comparison to other metastatic sites, however differences between BM themselves was not investigated 39 . The present work, together with those previously published 24,26,27,[40][41][42][43][44][45][46][47][48][49] , highlight the importance of (i) characterizing the BM microenvironment in individual patients, and (ii) adapting external RT to the presence of hypoxia for better tumor control. Zakaria and colleagues have highlighted the importance of using more functional MRI biomarkers, such as diffusion-MRI, rather than conventional contrast-enhanced MRI for RT planning to improve BM control 50 .…”

Motexafi n gadolinium injection for the treatment of brain metastases in patients with non-small cell lung cancer

“…RSR-13 is a synthetic allosteric modifier of hemoglobin (Hb), which decreases Hb-oxygen binding affinity, resulting in increased tumor oxygen concentration in tumor cells (Stea et al 2006). Suh et al conducted a Phase III trial, randomizing 538 patients with brain metastases to 30 Gy WBRT with supplemental oxygen with or without RSR-13 (Suh et al 2004).…”

Brain Tumors: Current Issues in Diagnosis and Management

“…101 Due to WBRT limitations, there is increasing interest in incorporating chemical modifiers with WBRT. Motexafin-gadolinium, 102 efaproxaril, 103 and temozolomide 104,105 are among the many agents that are currently being investigated.…”