Treatment of metastatic colorectal cancer: focus on panitumumab

Figures & data

Figure 1 Simplified EGFR pathway.

Abbreviations: EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; mTOR, mammalian target of rapamycin; P13K, phosphatidylinositol 3-kinase.

Table 1 Summary of panitumumab monotherapy trials

Trial	KRAS status	Treatment regimen	PFS (months)	HR (P-value)	OS (months)	HR (P-value)	ORR
Phase III
Van Cutsem et al^Citation31 (n=463)	Unselected	BSC + Pan	8	0.54 (<0.0001)	NR	1	10%
		BSC	7.3		NR		0%
	KRAS-WT	BSC + Pan	12.3	0.45 (<0.0001)	8.1	0.99	17%
		BSC	7.3		7.6		0%
	KRAS-MT	BSC + Pan	7.4	0.99	4.9	1.02	0%
		BSC	7.3		4.4		0%
ASPECCT^Citation33 (n=1,010)	KRAS-WT exon 2	Pan	4.1	1	10.4	0.97 (0.0007)	22%
		Cetuximab	4.4		10		19.8%
Phase II
Hecht et al^Citation42 (n=148)	Unselected	Pan	14 weeks		9		9%
Muro et al^Citation49 (n=52)	Unselected	Pan	8 weeks		9.3		14%

Abbreviations: PFS, progression-free survival; HR, hazard ratio; OS, overall survival; ORR, overall response rate; BSC, best supportive care; Pan, panitumumab; NR, not reported; n, number of patients.

Table 2 Summary of first-line panitumumab trials

Trial	KRAS status	Treatment regimen	PFS (months)	HR (P-value)	OS (months)	HR (P-value)	ORR
Phase III
PRIME^Citation25 (n=1,183)	KRAS-WT	FOLFOX4 + Pan	10	0.8 (0.01)	23.8	0.83 (0.03)	57%
		FOLFOX4	8.6		19.4		48%
	KRAS-MT	FOLFOX4 + Pan	7.4	1.27 (0.02)	15.5	1.17 (0.014)	40%
		FOLFOX4	9.2		19.2		41%
Phase II
PEAK^Citation35 (n=285)	KRAS-WT exon 2	FOLFOX + Pan	10.9	0.87 (0.35)	34.2	0.62 (0.009)	57.8%
		FOLFOX + Bev	10.1		24.3		53.5%
Kohne et al^Citation50 (n=154)	Unselected	FOLFIRI + Pan	7.6		NR		49%
	KRAS-WT	FOLFIRI + Pan	8.9		NR		56%
	KRAS-MT	FOLFIRI + Pan	7.2		NR		38%
Berlin et al^Citation51 (n=43)	Unselected	FOLFIRI + Pan	10.9		22.5		42%
	Unselected	IFL + Pan	5.6		17		46%

Abbreviations: PFS, progression-free survival; HR, hazard ratio; OS, overall survival; ORR, overall response rate; Pan, panitumumab; FOLFOX, folinic acid/infusional 5-fluorouracil/oxaliplatin; Bev, bevacizumab; FOLFIRI, folinic acid/infusional 5-fluorouracil/irinotecan; IRL, folinic acid/bolus 5-fluorouracil/irinotecan; n, number of patients; NR, not reported.

Table 3 Summary of second-line panitumumab trials

Trial	KRAS status	Treatment regimen	PFS (months)	HR (P-value)	OS (months)	HR (P-value)	ORR
Phase III
Peeters et al^Citation36 (n=1,186)	KRAS-WT	FOLFIRI + Pan	6.7	0.82 (0.023)	14.5	0.92 (0.37)	36%
		FOLFIRI	4.9		12.5		10%
PICCOLO^Citation37 (n=460)	KRAS-WT	Irinotecan + Pan	NR	0.78 (0.015)	10.4	1.01 (0.91)	34%
		Irinotecan	NR		10.9		12%
Phase II
SPIRITT^Citation38 n=182	KRAS-WT	FOLFIRI + Pan	7.7	1.01 (0.97)	18	1.06 (0.75)	32%
		FOLFIRI + Bev	9.2		21.4		19%
Cohn et al^Citation52 (n=116)	KRAS-WT	FOLFIRI + Pan	6	KRAS-WT vs KRAS-MT	11.5	KRAS-WT vs KRAS-MT	23%
	KRAS-MT	FOLFIRI + Pan	4.3		7.1		16%
				HR 0.8		HR 0.6
STEPP^Citation41 (n=87)	KRAS-WT	Iri/FOLFIRI + Pan	5.5		13.7		16%
	KRAS-MT	Iri/FOLFIRI + Pan	3.3		13.3		8%

Abbreviations: PFS, progression-free survival; HR, hazard ratio; OS, overall survival; ORR, overall response rate; FOLFIRI, folinic acid/infusional 5-fluorouracil/irinotecan; Pan, panitumumab; Bev, bevacizumab; Iri, Irinotecan; n, number of patients; NR, not reported.

Van CutsemEPeetersMSienaSOpen-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancerJ Clin Oncol200725131658166417470858

 PubMed Web of Science ®Google Scholar

PriceTJPeetersMKimTWPanitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 studyLancet Oncol201415656957924739896

 PubMed Web of Science ®Google Scholar

HechtJRPatnaikABerlinJPanitumumab monotherapy in patients with previously treated metastatic colorectal cancerCancer2007110598098817671985

 PubMed Web of Science ®Google Scholar

MuroKYoshinoTDoiTA phase 2 clinical trial of panitumumab monotherapy in Japanese patients with metastatic colorectal cancerJpn J Clin Oncol200939532132619287023

 PubMed Web of Science ®Google Scholar

DouillardJYSienaSCassidyJRandomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME studyJ Clin Oncol2010284697470520921465

 PubMed Web of Science ®Google Scholar

SchwartzbergLSRiveraEKarthausMPEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOL-FOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancerJ Clin Oncol201432212240224724687833

 PubMed Web of Science ®Google Scholar

KohneCHHofheinzRMineurLFirst-line panitumumab plus irinotecan/5-fluorouracil/leucovorin treatment in patients with metastatic colorectal cancerJ Cancer Res Clin Oncol20121381657221960318

 PubMed Web of Science ®Google Scholar

BerlinJPoseyJTchekmedyianSPanitumumab with irinotecan/ leucovorin/5-fluorouracil for first-line treatment of metastatic colorectal cancerClin Colorectal Cancer20076642743217531105

 PubMed Web of Science ®Google Scholar

PeetersMPriceTCervantesAFinal results from a randomized phase 3 study of FOLFIRI {+/−} panitumumab for second-line treatment of metastatic colorectal cancerAnn Oncol201425110711624356622

 PubMed Web of Science ®Google Scholar

SeymourMTBrownSRMiddletonGPanitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trialLancet Oncol201314874975923725851

 PubMed Web of Science ®Google Scholar

HechtJRCohnALDakhilSRSPIRITT (study 20060141): a randomized phase II study of FOLFIRI with either panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC)2013 Gastrointestinal Cancers SymposiumJanuary 24–26, 2013San Francisco, CA Abstract 454

 Google Scholar

CohnAShumakerGKhandelwalPAn open-label, single-arm, phase 2 trial of panitumumab plus FOLFIRI as second-line therapy in patients with metastatic colorectal cancerClin Colorectal Cancer200110317117721855038

 PubMed Web of Science ®Google Scholar

LacoutureMEMitchellEPPiperdiBSkin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-Emptive Skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancerJ Clin Oncol20102881351135720142600

 PubMed Web of Science ®Google Scholar