The bevacizumab experience in advanced renal cell carcinoma

Figures & data

Table 1 Comparison between the 2 bevacizumab randomized controlled phase 3 trials in advanced RCC

	CALGB	AVOREN
Sample size	732	649
Median age, y	61	61
Male patients,%	73%	68%
Performance status (≥80% by KPS or ≥1 by ECOG)	98%	94%
Prior nephrectomy	85%	100%
MSKCC risk
Good	26%	27%
Intermediate	64%	56%
Poor	10%	9%
Unknown	0%	9%
Placebo-controlled	No	Yes
Maximum weeks of IFN-α allowed by trial	None	52
Assessment of efficacy	Investigator-assessed	Independent
Overall survival	18.3 vs 17.4 (stratified, P = 0.097)	23.3 vs 21.3 (stratified, P = 0.1291)
Progression-free survival, mo	8.5 vs 5.2	10.2 vs 5.4
Response rate	25.5% vs 13.1%	31% vs 13%

Abbreviations: RCC, renal cell carcinoma; MSKCC, Memorial Sloan-Kettering Cancer Center; IFN, interferon.

Table 2 Comparative incidences of toxicities among bevacizumab and the multityrosine kinase inhibitors used to treat advanced renal cell carcinoma

	Bevacizumab^Citation13,Citation16,Citation31^–^Citation33	Sunitinib^Citation58,Citation61^–^Citation66	Sorafenib^Citation58,Citation61,Citation65,Citation80^–^Citation83	Pazopanib^Citation84^–^Citation86
Fatigue	<10%–93%	54%–58%	29%–37%	19%–46%
Decline in cardiac ejection fraction	<1%	13%–21%	<1%–5%a	<1%
Hypertension	20%–28%	30%	17%–22%	40%–47%
Acute coronary syndrome, chest pain	1%–3%	NR	2.9%	5%
Arteriothrombolic events	1%–4%	1.3%	1.7%	3%
Venothrombolic events	3%–4%	2%	<1%	NR
Hemorrhage/bleeding	5%–33%	18%–30%	15%	16%
Proteinuria	18%–71%	Case reportsb	Case reportsb	9%
Rash	0%–<5%	24%–27%	40%–41%	8%–16%
Hand–foot syndrome	0%–<5%	21%–29%	30%–60%	6%–11%
Diarrhea	20%–21%	58%–61%	43%–55%	52%–63%
Nausea	<10%–58%	49%–52%	19%–23%	26%–42%
Vomiting	<10%	28%–32%	12%–16%	20%–21%
Mucositis/stomatitis	0%–,5%	30%–43%	5%–17%	<10%
Myelosuppression
Leukopenia	NR	78%	>10%	35%–37%
Neutropenia	7%–43%	72%–77%	18%	27%–34%
Anemia	16%	71%–79%	8%–44%	<10%–26%
Thrombocytopenia	6%–10%	65%–68%	12%	26%–32%
Transaminitis	8%	46%–56%	1%–10%	53%–54%
Hyperbilirubinemia	0%–5%	12%–20%	<1%	28%–36%
Hypothyroidism	<1%	14%	<1%	4%
Infusion reaction	<3%	n/a	n/a	n/a

Notes:

a Unclear if the higher 5% incidence was associated with clinical heart failure in the Schmidinger study.

b Postmarketing case reports.

Abbreviations: NA, not applicable; NR, not reported.

Table 3 Efficacy results for the phase 3 VEGF inhibitor randomized controlled trials in treatment-naïve advanced RCC

Trial	No	PFS, mo	OS, mo	ORR,%	Time to response, mo	Median duration response, mo
Bevacizumab + IFN-α vs placebo/IFN-α (AVOREN)^Citation30,Citation31	649	10.2 vs 5.4 (P = 0.0001)	23.3 vs 21.3 (stratified, P = 0.1291)	31 vs 13	2.2 vs 3.7	13.5 vs 11.1
Bevacizumab + IFN-α vs IFN-α (CALGB 90206)^Citation32,Citation33	732	8.5 vs 5.2 (P < 0.0001)	18.3 vs17.4 (stratified, P = 0.097)	25.5 vs 13.1	NR	11.9 vs 8.7
Sunitinib vs IFN-α62,63	750	11 vs 5 P < 0.001	26.4 vs 21.8 (P = 0.051, stratified, P = 0.049)	47 vs 12	NR	NR
Pazopanib vs BSC/placebo^Citation86	233	11.1 vs 2.8 P < 0.0001	NR	32 vs 4	3.0a	14.7a

Note:

a All treatment groups, not just treatment naïve.

Abbreviations: RCC, renal cell carcinoma; PFS, progression-free survival; OS, overall survival; IFN, interferon; NR, not reported; BSC, best supportive care.

Bevacizumab [package insert]. Genentech; 2009. South San Francisco, CA, USA.

 Google Scholar

YangJCHaworthLSherryRMA randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancerN Engl J Med200334942743412890841

 PubMed Web of Science ®Google Scholar

EscudierBPluzanskaAKoralewskiPBevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trialLancet20073702103211118156031

 PubMed Web of Science ®Google Scholar

RiniBIHalabiSRosenbergJEBevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206J Clin Oncol2008265422542818936475

 PubMed Web of Science ®Google Scholar

ChoueiriTKSchutzFAJeYRosenbergJEBellmuntJRisk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trialsJ Clin Oncol2010282280228520351323

 PubMed Web of Science ®Google Scholar

LenihanDJTyrosine kinase inhibitors: can promising new therapy associated with cardiac toxicity strengthen the concept of teamwork?J Clin Oncol2008265154515518838702

 PubMed Web of Science ®Google Scholar

TelliMLWittelesRMFisherGASrinivasSCardiotoxicity associated with the cancer therapeutic agent sunitinib malateAnn Oncol2008191613161818436521

 PubMed Web of Science ®Google Scholar

SchmidingerMZielinskiCCVoglUMCardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinomaJ Clin Oncol2008265204521218838713

 PubMed Web of Science ®Google Scholar

Sorafenib [package insert]. Bayer Pharmaceutical; 2009. Wayne, NJ, USA.

 Google Scholar

EscudierBSzczylikCHutsonTERandomized phase II trial of first-line treatment with sorafenib versus interferon alfa-2a in patients with metastatic renal cell carcinomaJ Clin Oncol2009271280128919171708

 PubMed Web of Science ®Google Scholar

Votrient [prescribing information]. GlaxoSmithKline; 2010. Research Triangle, NC, USA.

 Google Scholar

SternbergCNDavisIDMardiakJPazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trialJ Clin Oncol2010281061106820100962

 PubMed Web of Science ®Google Scholar

EscudierBBellmuntJNegrierSPhase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): f inal analysis of overall survivalJ Clin Oncol20101214412150

 Google Scholar

RiniBIHalabiSRosenbergJEPhase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206J Clin Oncol20102137214320368558

 PubMed Web of Science ®Google Scholar