Vectibix® is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC):Read More
Early targeted therapy with Vectibix® + FOLFOX4 improved survival
in newly diagnosed WT RAS* mCRC patients2,3
Median PFS
Months (95% CI)
HR = 0.72 (95% CI: 0.58-0.90)
Median OS
Months (95% CI)
HR = 0.77 (95% CI: 0.64-0.94)
There are no OS or PFS benefits in patients with RAS-mutant mCRC treated with Vectibix®2
PRIME PHASE 3 STUDY DESIGN
PRIME was an open label, randomized (1:1), multicenter study of Vectibix® Q2W + FOLFOX4 vs FOLFOX4 Q2W alone in treatment of newly diagnosed mCRC patients. Among the study population of 1,183 patients with previously untreated mCRC, 656 were WT KRAS† patients. The extended RAS population in the post-hoc analysis consisted of 512 WT RAS* patients. Of these, 259 received Vectibix® + FOLFOX4 and 253 received FOLFOX4 alone.2,3
*Defined as wild type in both KRAS and NRAS.1
†Exon 2 in codons 12 and 13.1
1L = first-line; CI = confidence interval; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; HR = hazard ratio; mCRC = metastatic colorectal cancer; OS = overall survival; PFS = progression-free survival; PRIME = Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy; Q2W = every 2 weeks; WT = wild type.
PARADIGM Primary Analysis
A head-to-head, prospective, randomized (1:1), multicenter, open-label, phase 3 study comparing 1L Vectibix® (panitumumab) + mFOLFOX6 vs Avastin® (bevacizumab) + mFOLFOX6 in 802 Japanese patients with WT RAS* mCRC and left-sided primary tumors. Four hundred patients were randomized to the Vectibix® + mFOLFOX6 arm, and 312 of those patients had left-sided primary tumors; 402 patients were randomized to Avastin® + mFOLFOX6, and 292 of those patients had left-sided primary tumors. The primary endpoint of the study was OS in the left-sided population and, if the results were significant, OS in the overall population. Secondary endpoints included PFS, response rate (RR), duration of response (DOR), and curative resection (R0) in both left-sided and overall populations.
The PARADIGM Post Hoc Biomarker Analysis investigates tumor sidedness along with 3 clinically relevant biomarkers: RAS, BRAF, and microsatellite status4
Baseline plasma ctDNA (>10 ng/mL and >10 nM DNA) was sequenced using a custom panel (PlasmaSELECT-R 91, PGDx) to detect 90 mutations, 26 amplifications, and 3 rearrangements in mCRC-related genes, as well as MSI in 250kb targeted regions using stringent quality criteria.
90% of patients enrolled in PARADIGM with left-sided tumors were Double WT Non-MSI-H (n = 497/554)4
*Double WT Non-MSI-H = WT RAS + WT BRAF V600E + MSS or MSI-L.4
†Some patients had multiple primary lesions in both the left and right sides.
ctDNA = circulating tumor DNA; Double WT Non-MSI-H = WT RAS + WT BRAF V600E + MSS or MSI-L; mCRC = metastatic colorectal cancer; MSI-H = microsatellite instability-high; MSI-L = microsatellite instability-low; MSS = microsatellite stable; MT = mutant type; WT = wild type.
Vectibix® vs Avastin® in combination with mFOLFOX6
Post hoc analysis: study was not powered to evaluate efficacy or statistical significance
Double WT Non-MSI-H = WT RAS + WT BRAF V600E + MSS or MSI-L; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; mCRC = metastatic colorectal cancer; mOS = median overall survival; MSI-H = microsatellite instability-high; MSI-L = microsatellite instability-low; MSS = microsatellite stable; WT = wild type.
Vectibix® vs Avastin® in combination with mFOLFOX6
Post hoc analysis: study was not powered to evaluate efficacy or statistical significance.
FOLFOX = fluorouracil, leucovorin, and oxaliplatin; mCRC = metastatic colorectal cancer; mOS = median overall survival; MSI-H = microsatellite instability-high.
Vectibix® vs Avastin® in combination with mFOLFOX6
Post hoc analysis: study was not powered to evaluate efficacy or statistical significance.
CI = confidence interval; Double WT Non-MSI-H = WT RAS + WT BRAF V600E + MSS or MSI-L; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; HR = hazard ratio; mCRC = metastatic colorectal cancer; MSI-H = microsatellite instability-high; MSI-L = microsatellite instability-low; MSS = microsatellite stable; PFS = progression-free survival; WT = wild-type.
Vectibix® vs Avastin® in combination with mFOLFOX6
Post hoc analysis: study was not powered to evaluate efficacy or statistical significance.
CI = confidence interval; Double WT Non-MSI-H = WT RAS + WT BRAF V600E + MSS or MSI-L; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; HR = hazard ratio; mCRC = metastatic colorectal cancer; mOS = median overall survival; MSI-H = microsatellite instability-high; MSI-L = microsatellite instability-low; MSS = microsatellite stable; PFS = progression-free survival; WT = wild type.
Adverse events of any grade ≥ 20% in either treatment arm.1
Dermatological toxicity reactions occurred predominantly in the Vectibix® arm.1 Prophylactic measures may help reduce the severity of dermatologic toxicities.5 Examples of prophylactic skin treatments can be found here.
The rates of adverse events observed in patients included the Post Hoc Biomarker Analysis were consistent with the rates of adverse events seen in the overall PARADIGM study.6
PARADIGM = Panitumumab and RAS, Diagnostically useful Gene Mutation for metastatic colorectal cancer (mCRC).
DOSING
STUDY POPULATION
OUTCOMES
5-FU = 5-fluorouracil; EGFR = epidermal growth factor receptor; mCRC = metastatic colorectal cancer; PARADIGM = Panitumumab and RAS, Diagnostically useful Gene Mutation for metastatic colorectal cancer (mCRC); US = United States; USPI = United States Prescribing Information.
Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix® monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].
Please see Vectibix® full Prescribing Information, including Boxed WARNING.
Vectibix® is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC):
Vectibix® is not indicated for the treatment of patients with RAS-mutant mCRC or for whom RAS mutation status is unknown.
Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix® monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].
References
1. Watanabe J, Muro K, Shitara K, et al. JAMA. 2023;329:1271-1282. 2. Vectibix® (panitumumab) prescribing information, Amgen. 3. Douillard J-Y, Oliner KS, Siena S, et al. N Engl J Med. 2013;369:1023-1034. 4. Yamazaki K, Muro K, Watanabe J, et al. Presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 2-6, 2023; Chicago 5. Kobayashi Y, Komatsu Y, Yuki S, et al. Future Oncol. 2015;11:617-627. 6. Data on file, PARADIGM Post Hoc Biomarker Analysis Safety AEs; July 2021. 7. AVASTIN® (bevacizumab) prescribing information, Genentech. 8. Ma P, Yang BB, Wang YM, et al. J Clin Pharmacol. 2009;49:1142-1156. 9. Chen D, Li L, Zhang X, et al. Medicine (Baltimore). 2018;97:e0097. 10. Arnold D, Lueza B, Douillard JY, et al. Ann Oncol. 2017;28:1713-1729. 11. Tejpar S, Stintzing S, Ciardello F, et al. JAMA Oncol. 2017;3;194-201. 12. Loree JM, Dowers A, Tu D, et al. Clin Cancer Res. 2021;27:52-59.