REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours

Lévy, Christelle; Allouache, Djelila; Lacroix, Joëlle; Dugué, Audrey Emmanuelle; Supiot, S.; Campone, Mario; Mahé, M.‐A.; Kichou, Salim; Leheurteur, Marianne; Hanzen, C.; Diéras, V.; Kirova, Youlia; Campana, F.; Rhun, Émilie Le; Gras, L.; Bachelot, T; Sunyach, Marie Pierre; Hrab, Ioana; Geffrelot, Julien; Gunzer, K.; Constans, Jean-Marc; Grellard, Jean‐Michel; Clarisse, Bénédicte; Paolettí, Xavier

doi:10.1093/annonc/mdu465

Cited by 49 publications

(33 citation statements)

References 21 publications

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“…A retrospective analysis of a NSCLC cohort treated with bevacizumab followed by WBRT showed no increased toxicity with this treatment regimen, with median survival from WBRT of 3.2 months (28). Furthermore, the REBECA trial has confirmed that combined bevacizumab and WBRT appears tolerable for brain metastases treatment (29).…”

Section: Discussionmentioning

confidence: 93%

Bevacizumab in Patients with Nonsquamous Non–Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study

Besse

Moulec

Mazières

et al. 2015

Clinical Cancer Research

192

120

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Purpose: The phase II prospective, noncomparative BRAIN study (NCT00800202) investigated efficacy and safety of bevacizumab in chemotherapy-na€ ve or pretreated patients with nonsmall cell lung cancer (NSCLC) and asymptomatic untreated brain metastases to provide data in this previously unexplored subgroup.Experimental Design: Patients with stage IV nonsquamous NSCLC, Eastern Cooperative Oncology Group performance status 0-1, and untreated, asymptomatic brain metastases received first-line bevacizumab (15 mg/kg) plus carboplatin (area under the curve Â6) and paclitaxel (200 mg/m 2 ) every 3 weeks (B þ CP), or second-line bevacizumab plus erlotinib (150 mg/d; B þ E). Six-month progression-free survival (PFS) was the primary endpoint. The trial could be stopped if there were more than three (B þ CP) or more than two (B þ E) intracranial hemorrhages.Results: In first-line B þ CP cohort (n ¼ 67), 6-month PFS rate was 56.5% with a median PFS of 6.7 months [95% confidence interval (CI), 5.7-7.1] and median overall survival (OS) of 16.0 months. Investigator-assessed overall response rate (ORR) was 62.7%: 61.2% in intracranial lesions and 64.2% in extracranial lesions. Because of low enrolment (n ¼ 24), efficacy results for the second-line B þ E cohort were exploratory only; 6-month PFS rate was 57.2%, median PFS was 6.3 months (95% CI, 3.0-8.4), median OS was 12.0 months, and ORR was 12.5%. Adverse events were comparable with previous trials of bevacizumab. One grade 1 intracranial hemorrhage occurred and resolved without sequelae.Conclusions: The BRAIN study demonstrates encouraging efficacy and acceptable safety of bevacizumab with first-line paclitaxel and carboplatin in patients with NSCLC and asymptomatic, untreated brain metastases.

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Section: Discussionmentioning

confidence: 93%

Bevacizumab in Patients with Nonsquamous Non–Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study

Besse

Moulec

Mazières

et al. 2015

Clinical Cancer Research

192

120

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“…32 In the recent Safety Evaluation of a Combination of Brain Radiation Therapy and Bevacizumab for Treatment of Brain Metastasis (REBECA) phase I trial Bev was evaluated in combination with WBRT in patients with brain metastases from solid tumors and achieved some encouraging results, which suggested a potential synergistic effect between Bev and radiation therapy. 33 In this regard, it should be also noted that the bloodebrain barrier is disrupted during brain radiotherapy, hence, the penetration of chemotherapy drugs and Bev through it might be facilitated. 34 The treatment strategy we proposed showed a good safety profile.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin, Etoposide, and Bevacizumab Regimen Followed by Oral Etoposide and Bevacizumab Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer: A Single-Institution Experience

Petrioli

Roviello

Laera

et al. 2015

Clinical Lung Cancer

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“…136 Patients received 3 cycles of bevacizumab at escalating doses (5, 10, 15 mg/kg every 2 weeks) with WBRT (30 Gy/15 fractions) administered from day 15 of bevacuzimab; 10 of the 19 patients had an intracranial treatment response at 3 months, with grade 1 and 2 toxicities occurring in 5 and 9 patients respectively; no grade ≥3 toxicity was reported. There is currently no published clinical data regarding the combination of VEGF-inhibitors and SRS in NSCLC patients.…”

Section: Nsclc With Unresectable Bm Was Presented At the Annual Europmentioning

confidence: 99%

Brain Metastases from NSCLC: Radiation Therapy in the Era of Targeted Therapies

Khalifa

Amini

Popat

et al. 2016

Journal of Thoracic Oncology

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Brain metastases (BMs) will develop in a large proportion of patients with NSCLC throughout the course of their disease. Among patients with NSCLC with oncogenic drivers, mainly EGFR activating mutations and anaplastic lymphoma receptor tyrosine kinase gene (ALK) rearrangements, the presence of BM is a common secondary localization of disease both at the time of diagnosis and at relapse. Because of the limited penetration of a wide range of drugs across the blood-brain barrier, radiotherapy is considered the cornerstone of treatment of BMs. However, evidence of dramatic intracranial response rates has been reported in recent years with targeted therapies such as tyrosine kinase inhibitors and has been supported by new insights into pharmacokinetics to increase rates of tyrosine kinase inhibitors' penetration of the cerebrospinal fluid (CSF). In this context, the combination of brain radiotherapy and targeted therapies seems relevant, and there is a strong radiobiological rationale to harness the radiosentizing effect of the drugs. Nevertheless, to date, there is a paucity of high-level clinical evidence supporting the combination of brain radiotherapy and targeted therapies in patients with NSCLC and BMs, and there are often methodological biases in reported studies, such as the lack of stratification by mutation status. Moreover, among asymptomatic patients not suitable for ablative treatment, this strategy is challenged by the promising results associated with the administration of targeted therapies alone. Herein, we review the biological rationale to combine targeted therapies and brain radiotherapy for patients with NSCLC and BMs, report the clinical data available to date, and discuss future directions to improve outcome in this group of patients.

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REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours

Abstract: Bevacizumab combined with WBRT appears to be a tolerable treatment of BM. DL3 warrants further efficacy evaluation based on the favourable safety/efficacy balance. ClinicalTrials.gov Identifier: NCT01332929.

Cited by 49 publications

References 21 publications

Bevacizumab in Patients with Nonsquamous Non–Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study

Bevacizumab in Patients with Nonsquamous Non–Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study

Cisplatin, Etoposide, and Bevacizumab Regimen Followed by Oral Etoposide and Bevacizumab Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer: A Single-Institution Experience

Brain Metastases from NSCLC: Radiation Therapy in the Era of Targeted Therapies

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