Previous Bevacizumab and Efficacy of Later Anti–Epidermal Growth Factor Receptor Antibodies in Metastatic Colorectal Cancer: Results From a Large International Registry

Burge, Matthew; Semira, Christine; Lee, Belinda; Lee, Margaret; Kosmider, Suzanne; Wong, Rachel; Shapiro, Jeremy; Ma, Brigette; Dean, Andrew; Zimet, Allan; Steel, Simone; Lok, Sheau Wen; Torres, Javier; Eastgate, Melissa; Wong, Hui Li; Gibbs, Peter

doi:10.1016/j.clcc.2018.05.009

Cited by 8 publications

(6 citation statements)

References 23 publications

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“…Because this was a retrospective study and we did not have access to tumour blocks, we could not assess the all-RAS mutational status in our patients. A median interval of 6 months from the last dose of bevacizumab to the first dose of cetuximab was reported and they further split the group that received previous bevacizumab into two (< 6 months vs. > 6 months) and found that an interval of < 6 months was associated with lower PFS, but only in right-sided tumours [2]. A different study showed that the shorter the interval, the higher the probability of interfering with the efficacy of EGFRIs [23].…”

Section: Resultsmentioning

confidence: 99%

Efficacy of Cetuximab/Panitumumab After Previous Bevacizumab in Metastatic Colorectal Cancer

Gherman¹

2020

FARMACIA

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The optimal sequence of the targeted therapies in metastatic colorectal cancer is not established. We aimed to analyse if previous administration of bevacizumab impacts the response to epidermal growth factor receptor inhibitors in subsequent lines of therapy. It was performed a retrospective analysis on KRAS or KRAS/NRAS wild-type metastatic colorectal cancer patients that received an epidermal growth factor receptor inhibitor in the second or later lines of therapy and their outcom es were analysed according to previous exposure to bevacizumab. 85 metastatic colorectal cancer patients were included, of whom 22 had received previous chemotherapy (group A) and 63 previous chemotherapy plus bevacizumab (group B). The overall survival was significantly higher in the group B (35.6 months versus 24.8 months, p = 0.01). The overall survival and progression-free survival calculated from the start of the epidermal growth factor receptor inhibitor did not significantly differ between the groups. The multivariate analysis revealed that using bevacizumab did not significantly impact the survival. Our results show that previous administration of bevacizumab does not influence the efficacy of epidermal growth factor receptor inhibitors in later lines of treatment. RezumatSecvența optimă a tratamentelor moleculare țintite în cancerul colorectal metastatic încă nu este stabilită. Obiectivul studi ului a fost de a analiza dacă răspunsul terapeutic la inhibitorii receptorului factorului de creștere epidermal în liniile ulterioare de tratament este influențat de administrarea anterioară de bevacizumab. A fost efectuată o analiză retrospectivă a pacienților cu cancer colorectal metastatic fără mutații KRAS sau KRAS/NRAS, care au primit tratament cu un inhibitor al receptorului factorului de creștere epidermal în linia a doua sau ulterioară de tratament și a fost analizată evoluția clinică a pacienților în funcție de expunerea anterioară la bevacizumab. În studiu au fost incluși 85 pacienți cu cancer colorectal metastatic, dintre care 22 au primit chimioterapie anterioară singură (grupul A), iar 63 au primit chimioterapie anterioară cu bevacizumab (grupul B). Supraviețuirea globală a fost semnificativ mai mare în grupul B (35,6 luni versus 24,8 luni, p = 0,01). Supraviețuirea globală și supraviețuirea liberă de progresia bolii calculate de la debutul liniei cu agentul inhibitor al receptorului factorului de creștere epidermal nu a fost semnificativ diferită între cele două grupuri. Analiza multivariată a supraviețuirii a arătat c ă administrarea bevacizumabului nu a influențat semnificativ supraviețuirea. Rezultatele studiului arată că administrarea anterioară de bevacizumab nu influențează eficiența inhibitorilor factorului de creștere epidermal în liniile ulterioare de tratament.

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Section: Resultsmentioning

confidence: 99%

Efficacy of Cetuximab/Panitumumab After Previous Bevacizumab in Metastatic Colorectal Cancer

Gherman¹

2020

FARMACIA

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“…Alternatively, a small retrospective analysis that investigated the survival of KRAS WT patients who were sequentially treated with cetuximab and bevacizumab reported that patients receiving bevacizumab first had similar survival outcomes compared to patients receiving cetuximab first (PFS: 13 vs 10 months, P =0.798; OS: 44 vs 39 months, P =0.862) 29. Burge et al analyzed a multicenter registry and found that initial bevacizumab use did not impact the efficacy of EGFR antibodies in subsequent therapy as PFS and OS from anti-EGFR mAb commencement were not significantly different from prior bevacizumab use,32 which is similar to other reports 30,31. In addition, a longer gap between bevacizumab and anti-EGFR mAb (>6 months) was linked to a longer median PFS in right-sided tumors, while left-sided tumors had no difference, which may reflect a distinct subgroup with a superior prognosis in right-sided tumors 32…”

Section: Resultsmentioning

confidence: 99%

“…Burge et al analyzed a multicenter registry and found that initial bevacizumab use did not impact the efficacy of EGFR antibodies in subsequent therapy as PFS and OS from anti-EGFR mAb commencement were not significantly different from prior bevacizumab use,32 which is similar to other reports 30,31. In addition, a longer gap between bevacizumab and anti-EGFR mAb (>6 months) was linked to a longer median PFS in right-sided tumors, while left-sided tumors had no difference, which may reflect a distinct subgroup with a superior prognosis in right-sided tumors 32…”

Section: Resultsmentioning

confidence: 99%

<p>Optimizing sequential treatment with anti-EGFR and VEGF mAb in metastatic colorectal cancer: current results and controversies</p>

Chen¹,

Gu²,

Wang³

2019

CMAR

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Anti-EGFR mAb (cetuximab or panitumumab) and anti-VEGF mAb (bevacizumab) are the two main targeted agents available for RAS wild-type (WT) metastatic colorectal cancer (mCRC) treatment. Nonetheless, three head-to-head clinical trials evaluating anti-EGFR mAb vs -VEGF mAb in first-line treatment failed to conclude a uniform result. Recently, a few small clinical studies revealed that prior use of bevacizumab may impair the effect of cetuximab or panitumumab. Preclinical studies have also suggested that pretreatment with bevacizumab may lead to simultaneous resistance to anti-EGFR mAb. Therefore, we performed this review to summarize the available data regarding the optimal sequential treatment of anti-EGFR and -VEGF mAb for RAS or KRAS WT mCRC and discuss the potential mechanisms that may explain this phenomenon. Primary tumor location and early tumor shrinkage have emerged as new potential prognostic and predictive factors in mCRC. We also collected information to explore whether these factors affect the optimal sequencing of targeted therapy in mCRC. However, definite conclusions cannot be made, and we can only speculate on optimal treatment recommendations based on the contradictory results.

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“…On the 12th month after treatment, the volumes of the thyroid group and non-hypothyroidism group decreased by 14.15% and 10.60%, respectively. Some studies (12)(13)(14) have shown that thyroid dysfunction is caused by TKIs, which may be due to the inhibition of VEGFR2-induced degradation of the capillary network in the glands. These dysfunctions mainly manifest in poor vascular structure, fibrin deposition, and blood flow stagnation, followed by the loss of vascular endothelial cells and a decrease of thyroid capillary density, which can be as high as 68%.…”

Section: Discussionmentioning

confidence: 99%

Sonography monitoring of thyroid morphology and function in patients with metastatic renal cell carcinoma treated with targeted drugs

Liu

Chen

et al. 2020

Ann Palliat Med

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Backgrounds: The incidence rate of renal cell carcinoma (RCC) has gradually increased worldwide over the past decade. Targeted therapy is the primary method for treating metastatic renal cell carcinoma (mRCC), and the development of thyroid dysfunction is one of the most common adverse reactions of this treatment.Therefore, this study aimed to assess the value of sonography in monitoring the morphology and functions of the thyroid in metastatic renal cell carcinoma patients treated with targeted drugs.Methods: In total, 37 patients from September 2016 to April 2019 with clinically confirmed mRCC that were treated with targeted drugs (19 with sunitinib and 18 with sorafenib) were enrolled in this study.The enrolled patients were divided into the hypothyroidism group and the non-hypothyroidism groups according to the changes in the serum concentration of the thyroid-stimulating hormone (TSH) during the treatment period. The serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), and TSH were measured by the Roche method before and after treatment. Simultaneously, the major axis, transverse diameter, and anteroposterior diameter of the bilateral lobes and isthmus of the thyroid gland were measured by ultrasound, and every thyroid volume was calculated. The changes in the thyroid volume, the thyroid volume change rate, and the homochronous serum concentration of TSH, FT3, FT4 in the hypothyroidism group, and the non-hypothyroidism group were then compared to assess the value of using sonography for monitoring the changes of thyroid morphology and functions.Results: In total, 20 patients had hypothyroidism (hypothyroidism group), while 17 patients did not have hypothyroidism (non-hypothyroidism group). The thyroid volumes in both groups decreased gradually after targeted therapy. In the 1 st , 2 nd , 3 rd , 4 th , 5 th , 6 th , 9 th , and 12th month after the treatment, the rate of change in thyroid volume in the hypothyroidism group (n=20) was 0.84 (0.47)%, 3.36 (1.34)%, 6.95

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Previous Bevacizumab and Efficacy of Later Anti–Epidermal Growth Factor Receptor Antibodies in Metastatic Colorectal Cancer: Results From a Large International Registry

Abstract: Previous bevacizumab use had no effect on the activity of subsequent EGFRIs. The apparent effect of time between biologic agents in right-sided tumors might reflect patient selection.

Cited by 8 publications

References 23 publications

Efficacy of Cetuximab/Panitumumab After Previous Bevacizumab in Metastatic Colorectal Cancer

Efficacy of Cetuximab/Panitumumab After Previous Bevacizumab in Metastatic Colorectal Cancer

<p>Optimizing sequential treatment with anti-EGFR and VEGF mAb in metastatic colorectal cancer: current results and controversies</p>

Sonography monitoring of thyroid morphology and function in patients with metastatic renal cell carcinoma treated with targeted drugs

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