408 STUDY
A randomized, open-label, active-controlled, multicentre, phase 3 study1

Demonstrated safety profile in the phase 3 408 STUDY
  • Adverse Reactions

    Most common (≥20%*) adverse reactions in chemorefractory patients with WT KRAS† mCRC1

    System Organ Class Preferred Term Vectibix + BSC (n=123) BSC alone (n=120)
    Any Grade
    n (%)    		 Grade 3–4
    n (%)         		Any Grade
    n (%)     		Grade 3–4
    n (%)
    Gastrointestinal disorders Diarrhea 30 (24) 3 (2) 13 (11) NR
    General disorders and administration site conditions Fatigue 40 (33) 6 (5) 15 (13) 4 (3)
    Infections and infestations Paronychia 41 (33) 4 (3) NR NR
    Respiratory, thoracic, and mediastinal disorders Cough 24 (20) NR 9 (8) NR
    Skin and subcutaneous tissue disorders Erythema 86 (70) 10 (8) 1 (<1) NR
    Pruritus 83 (67) 4 (3) 2 (2) NR
    Dermatitis acneiform 72 (59) 9 (7) 1 (<1) NR
    Rash 25 (20) 2 (2) 1 (<1) NR
    Exfoliative rash 31 (25) 4 (3) NR NR
    Skin fissures 30 (24) 3 (2) NR NR
    Adapted from the Product Monograph.1

    Most common (≥20%*) adverse reactions in patients with WT RAS mCRC1

    System Organ Class Preferred Term Vectibix + BSC (n=72) BSC alone (n=64)
    Any Grade
    n (%)    		 Grade 3–4
    n (%)         		Any Grade
    n (%)         		Grade 3–4
    n (%)
    Gastrointestinal disorders Diarrhea 16 (22) NR 5 (8) NR
    General disorders and administration site conditions Fatigue 28 (39) 2 (3) 9 (14) 1 (2)
    Infections and infestations Paronychia 30 (42) 4 (6) NR NR
    Respiratory, thoracic, and mediastinal disorders Cough 15 (21) NR 5 (8) NR
    Skin and subcutaneous tissue disorders Pruritus 51 (71) 4 (6) 2 (3) NR
    Erythema 49 (68) 4 (6) 1 (2) NR
    Dermatitis acneiform 45 (63) 5 (7) NR NR
    Skin fissures 22 (31) 1 (1) NR NR
    Exfoliative rash 21 (29) 2 (3) NR NR
    Adapted from the Product Monograph.1
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STUDY DESIGN
BASELINE
CHARACTERISTICS
Learn about the 408 Study by reading the publication.
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* In the Vectibix + BSC arm.

† KRAS (exon 2).

BSC, best supportive care; KRAS, Kirsten rat sarcoma viral oncogene homologue; NR, not reported in the Vectibix Product Monograph; mCRC, metastatic colorectal cancer;
RAS, Rat sarcoma viral oncogene homologue; WT, wild-type.

Baseline characteristics

All patients (n=463)4,5

Characteristics Vectibix + BSC (n=231) BSC alone (n=232)
Age
Mean age (range), years 61.2 (10.3) 61.4 (10.8)
Gender
Male (n) 146 148
Female (n) 85 84
Ethnicity
White (%) 99 98
Primary Tumour Type
Colon (%) 66 68
Rectal (%) 34 32
All patients (n=463)
Eastern Cooperative Oncology Group (ECOG) Performance Status
0 40%
1 45%
2 14%
3 1%
Prior fluoropyrimidine, irinotecan, and oxaliplatin chemotherapy
2 lines 100%
3 lines 37%
>3 lines 6%
Patient eligibility:4
  • ≥18 years old with pathologic diagnosis of metastatic colorectal adenocarcinoma and radiologic documentation of disease progression during or within 6 months following the last administration of fluoropyrimidine, irinotecan, and oxaliplatin.
  • Adequate exposure to prior chemotherapy, with average dose-intensity of irinotecan (≥65mg/m2 per week) and of oxaliplatin (≥30mg/m2 per week).
  • Two or three prior chemotherapy regimens for metastatic colorectal cancer.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–2.
  • ≥1% EGFR-positive membrane staining in evaluated tumour cells (primary or metastatic) by immunohistochemistry.

BSC, best supportive care; ECOG, Eastern Cooperative Oncology Group.

408 WAS A MULTINATIONAL, RANDOMIZED, CONTROLLED PHASE 3 STUDY WITH THE FOLLOWING STUDY DESIGN1,4,5
463 patients with EGFR-expressing mCRC after confirmed failure on fluoropyrimidine-, oxaliplatin- and irinotecan-containing regimens were randomized 1:1 to one of two groups: Vectibix at dosing administration of 6 mg/kg every two weeks (Q2W) + BSC (n=231) or BSC (n=232). Tumours from the original patient population were retrospectively analyzed by tumour KRAS mutation status. Of the 427 patients who had a tumour sample analyzed for KRAS, 243 were determined to have wild-type KRAS and 184 were determined to have mutant KRAS. Among patients that were randomized to receive Vectibix + BSC, 124 had wild-type and 84 had mutant KRAS; among patients that were randomized to receive BSC alone, 119 had wild-type and 100 had mutant KRAS. Duration of treatment was until disease progression or treatment toxicity. The primary endpoint was progression-free survival, while secondary endpoints consisted of overall survival, objective response rate, and safety. Upon disease progression, 167 patients originally randomized to BSC alone treatment arm were eligible to crossover to optional treatment of Vectibix at dosing administration of 6 mg/kg every two weeks (Q2W) + BSC. 463 patients with EGFR-expressing mCRC after confirmed failure on fluoropyrimidine-, oxaliplatin- and irinotecan-containing regimens were randomized 1:1 to one of two groups: Vectibix at dosing administration of 6 mg/kg every two weeks (Q2W) + BSC (n=231) or BSC (n=232). Tumours from the original patient population were retrospectively analyzed by tumour KRAS mutation status. Of the 427 patients who had a tumour sample analyzed for KRAS, 243 were determined to have wild-type KRAS and 184 were determined to have mutant KRAS. Among patients that were randomized to receive Vectibix + BSC, 124 had wild-type and 84 had mutant KRAS; among patients that were randomized to receive BSC alone, 119 had wild-type and 100 had mutant KRAS. Duration of treatment was until disease progression or treatment toxicity. The primary endpoint was progression-free survival, while secondary endpoints consisted of overall survival, objective response rate, and safety. Upon disease progression, 167 patients originally randomized to BSC alone treatment arm were eligible to crossover to optional treatment of Vectibix at dosing administration of 6 mg/kg every two weeks (Q2W) + BSC.

* Vectibix is not indicated for patients with mutant RAS (KRAS/NRAS) or for whom RAS status is unknown.

Adapted from the Vectibix Product Monograph,1 Amado et al.,4 and Van Cutsem et al.5

BSC, best supportive care; EGFR, epidermal growth factor receptor; KRAS, Kirsten rat sarcoma viral oncogene homologue; mCRC, metastatic colorectal cancer; MT, mutant; NRAS, Neuroblastoma RAS viral oncogene homologue; Q2W, every 2 weeks; RAS, Rat sarcoma viral oncogene homologue; WT, wild-type.