Clinical study evaluating the effect of bevacizumab on the severity of zoledronic acid-related osteonecrosis of the jaw in cancer patients

Lescaille, Géraldine; Coudert, Amélie E.; Baaroun, Vanessa; Ostertag, Agnès; Charpentier, Emmanuel; Javelot, Marie-José; Toledo, Rafael; Goudot, P.; Azérad, J.; Berdal, Ariane; Spano, Jean‐Philippe; Ruhin, B.; Descroix, Vianney

doi:10.1016/j.bone.2013.10.002

Cited by 37 publications

(31 citation statements)

References 32 publications

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“…Finally, cases of positively adjudicated ONJ according to very strict criteria were only 89 (1.6 %)-37 (1.3 %) on zoledronic acid and 52 (1.8 %) on denosumab. Notably, in the three trials, there were 14 ONJ cases among 464 patients treated with an antiresorptive agent (zoledronic acid or denosumab) and antiangiogenic agents (3.0 %) versus 75 ONJ cases among 5,259 patients receiving zoledronic acid or denosumab without any antiangiogenic agents (1.4 %) [5]: This kind of data seems to enforce recent literature data suggesting possible higher ONJ risk from combination of antiresorptive and antiangiogenic agents [7,8].According to the paper by Saad et al [5], among 89 total adjudicated ONJ patients (treated either with zoledronic acid or denosumab) there were six RCC patients, out of a total number of enrolled RCC patients of 155 [1,4]. This 6/155 (3.9 %) ONJ frequency in RCC patients is more than twice as high, if compared with the entire patient population (1.6 %).…”

supporting

confidence: 61%

Osteonecrosis of the jaw (ONJ) in renal cell cancer patients after treatment including zoledronic acid or denosumab

Fusco

Bedogni

Campisi

2014

Support Care Cancer

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Dear Editor, The paper by Henry et al. published by Supportive Care in Cancer comparing efficacy of denosumab versus zoledronic acid in patients with bone metastases of advanced solid tumours [1] comes to integrate the original reports of three pivotal large randomized phase 3 trials [2][3][4], the publication by Saad et al. about osteonecrosis of the jaw (ONJ) in those three trials [5], and the combined outcome analysis by Lipton et al. [6].Henry et al.[1] reported outcomes of the single trial conducted on patients with solid tumours (except breast or prostate cancers, object of other two trials) [2,3], excluding patients with multiple myeloma: This ad hoc analysis confirmed the superiority of denosumab in delaying or preventing skeletal-related events [1]. Amongst side effects, after a median (Q1, Q3) time on study of 6.7 (3.2, 13.0) and 6.4 (3.1, 12.9)months in the two groups, ONJ was reported in six denosumab arm patients (0.8 %) and in nine zoledronic acid arm patients (1.1 %).We wish to underline some sparse data reported in the cited papers, focusing attention on occurrence of ONJ in patients with renal cell cancer (RCC) included in the trial.In the summary ONJ analysis [5] of the above-mentioned three randomized trials comparing zoledronic acid and denosumab in patients with several cancer types and conducted between 2006 and 2009, it appears that an "Oral Event Identified as Potential ONJ" was registered in 276 patients out of 5,723 (4.8 %). Finally, cases of positively adjudicated ONJ according to very strict criteria were only 89 (1.6 %)-37 (1.3 %) on zoledronic acid and 52 (1.8 %) on denosumab. Notably, in the three trials, there were 14 ONJ cases among 464 patients treated with an antiresorptive agent (zoledronic acid or denosumab) and antiangiogenic agents (3.0 %) versus 75 ONJ cases among 5,259 patients receiving zoledronic acid or denosumab without any antiangiogenic agents (1.4 %) [5]: This kind of data seems to enforce recent literature data suggesting possible higher ONJ risk from combination of antiresorptive and antiangiogenic agents [7,8].According to the paper by Saad et al. [5], among 89 total adjudicated ONJ patients (treated either with zoledronic acid or denosumab) there were six RCC patients, out of a total number of enrolled RCC patients of 155 [1,4]. This 6/155 (3.9 %) ONJ frequency in RCC patients is more than twice as high, if compared with the entire patient population (1.6 %).In recent years, bone metastatic RCC patients received routinely targeted therapy, as monoclonal anti-VEGF antibody (bevacizumab), tyrosin-kinase inhibitors (sunitinib, sorafenib, pazopanib), mTOR inhibitors (temsirolimus, everolimus). Several types of recent reports suggest a relatively high ONJ risk in RCC patients after a combination of bisphosphonates (mostly zoledronic acid) and antiangiogenic agents (mostly sunitinib) [9][10][11][12].The question is: could the antiangiogenic treatment have played a role in the 3.9 % ONJ rate among RCC patients in the trial illustrated by Henry et al.? Unfortunately, a...

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supporting

confidence: 61%

Osteonecrosis of the jaw (ONJ) in renal cell cancer patients after treatment including zoledronic acid or denosumab

Fusco

Bedogni

Campisi

2014

Support Care Cancer

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“…Lescaille et al [83]on the contrary found in their 42 ONJ case population that bevacizumab was associated to earlier onset, higher risk of spontaneous developing (without trigger) and higher number of jaw lesions.…”

Section: Bevacizumabmentioning

confidence: 87%

“…After observing cases of ONJ where patients were treated with antiangiogenic agents with concomitant or previous antiresorptive drugs, the clinical findings have been quite similar to those in patients taking BPs even after shorter treatment durations and/or lower cumulative dosages, hypothesizing a precipitating role for antiangiogenic agents: for example, Lescaille et al reported the onset of ONJ after a median of 12.4 months of bevacizumab and zoledronate in comparison with a median 22.9 months in patients who received only zoledronate. [83] Description of ONJ literature cases after antiangiogenic agents without history of antiresorptive drugs is variable; the ONJ clinical history (particularly presence or not of bone exposure, duration of exposure, and shortterm improvement or worsening) could be probably related to drug effects on soft tissues (gingival) and influenced by drug administration schedule. A peculiarity of these new classes of drugs, different from BPs, is their pharmacodynamics (without bone accumulation) and shorter half-life (e.g.…”

Section: Expert Opinionmentioning

confidence: 99%

Osteonecrosis of jaw beyond antiresorptive (bone-targeted) agents: new horizons in oncology

Fusco

Santini

Armento

et al. 2016

Expert Opinion on Drug Safety

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Introduction: Osteonecrosis of the jaw (ONJ) is a clinically important, potentially painful and debilitating condition, which can affect the quality of life of cancer patients. Since 2003, ONJ appeared as a Bisphosphonate(BP)-related class effect, and the term Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) was widespread. Areas Covered: Under discussion in this review is the fact that ONJ cases have been reported after treatment including antiangiogenic agents and other “targeted therapy”, with and without BPs. Consequently, the comprehensive term Medication-Related Osteonecrosis of the Jaw (MRONJ) has been introduced. The clinical aspects and the prognosis of ONJ associated with these new drugs are still less reported, but basing on their pharmacodynamics, they could be different from the well-known BRONJ. Accordingly, recommendations largely in use for BRONJ should be extended to these new forms, but critically applied and with respect to the individual risk assessment. Expert Opinion: There is a high risk of underdiagnoses for ONJ due to a lack of awareness, and too much restrictive or incomplete diagnostic criteria; at the same time, with regard to ONJ associated to the new non –antiresorptive agents, described here, we observe the strong need to improve the defining of any distinguished feature in their diagnosis, prevention and therapy

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“…The association between an increased risk of BRONJ and the administration of anti-angiogenic agents or other BPs has been investigated in a number of small scale studies (23,(30)(31)(32). There is a previous study that specifies the use of sunitinib and ZA as a predisposing factor to the development of BRONJ (30), and there are studies that report bevacizumab to be a risk factor (31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

“…There is a previous study that specifies the use of sunitinib and ZA as a predisposing factor to the development of BRONJ (30), and there are studies that report bevacizumab to be a risk factor (31)(32)(33). However, there are also studies stating that bevacizumab is not a risk factor (23,34).…”

Section: Discussionmentioning

confidence: 99%

Effect of the cumulative dose of zoledronic acid on the pathogenesis of osteonecrosis of the jaws

et al. 2015

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Abstract. Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe bone disease for which the pathogenetic mechanisms and risk factors are not fully understood. The present study evaluated the data of 652 patients with bone metastasis that had undergone treatment with biphosphonates. Subsequently, 24 patients with BRONJ and 20 control patients without BRONJ that were treated with zoledronic acid were enrolled. It was found that BRONJ occurred in 3.6% of patients. The mean age and the administration of dental treatment were found to be significantly associated with BRONJ development (P=0.049 and P=0.013, respectively). The cumulative dose median in the BRONJ group was found to be significantly higher compared with the cumulative dose average in the control group (P=0.037). In addition, at the time of BRONJ development, improvement in the disease was determined to be better in the BRONJ group than in the control group (P=0.031). The present study determined that age, the existence of dental extraction and the cumulative dose of zoledronate were all important risk factors in BRONJ development.

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Clinical study evaluating the effect of bevacizumab on the severity of zoledronic acid-related osteonecrosis of the jaw in cancer patients

Cited by 37 publications

References 32 publications

Osteonecrosis of the jaw (ONJ) in renal cell cancer patients after treatment including zoledronic acid or denosumab

Osteonecrosis of the jaw (ONJ) in renal cell cancer patients after treatment including zoledronic acid or denosumab

Osteonecrosis of jaw beyond antiresorptive (bone-targeted) agents: new horizons in oncology

Effect of the cumulative dose of zoledronic acid on the pathogenesis of osteonecrosis of the jaws

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