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Adverse Reactions
Most frequent (≥25%*) adverse reactions in previously untreated patients with WT RAS mCRC1
System Organ Class Preferred Term Vectibix + FOLFOX (n=256) FOLFOX alone (n=250) Any Grade
n (%)Grade 3–4
n (%)Any Grade
n (%)Grade 3–4
n (%)Gastrointestinal disorders Diarrhea 167 (65) 48 (19) 129 (52) 22 (9) Stomatitis 77 (30) 14 (5) 36 (14) 1 (<1) Abdominal pain 71 (28) 12 (5) 62 (25) 13 (5) General disorders and administration site conditions Fatigue 100 (39) 26 (10) 90 (36) 7 (3) Pyrexia 81 (32) 2 (<1) 71 (28) 7 (3) Mucosal inflammation 64 (25) 13 (5) 40 (16) 1 (<1) Metabolic and nutritional disorders Anorexia 93 (36) 11 (4) 66 (26) 5 (2) Hypomagnesemia 77 (30) 19 (7) 17 (7) NR Nervous system disorders Paraesthesia 83 (32) 23 (9) 75 (30) 15 (6) Skin and subcutaneous tissue disorders Rash 142 (55) 44 (17) 20 (8) 1 (<1) Dermatitis acneiform 86 (34) 26 (10) NR NR Pruritus 66 (26) 3 (1) 11 (4) NR Adapted from the Product Monograph.1 -
Tolerability Profile
Serious adverse reactions1
Proportion of patients with wild-type RAS mCRC treated
with Vectibix in combination with FOLFOX<65 years of age ≥65 years of age Discontinuation rates 13% 24% Most common serious AE with a difference in patient incidence greater than 5% Diarrhea in 5% Diarrhea in 17% Additional serious AEs Pyrexia in 4% Nausea in 4%
Mucosal inflammation in 4%
Dehydration in 4%
Colorectal cancer metastatic in 4%Rate of Grade ≥3 AEs 89% 93% Grade ≥3 AE reported at a higher incidence (≥5%) in patients ≥65 years of age compared with patients <65 years of age Stomatitis
Asthenia
Mucosal inflammation
AnorexiaAdapted from the Product Monograph.1The commonly (2%) reported adverse reactions leading to discontinuation in patients with wild-type RAS mCRC receiving Vectibix (panitumumab) were rash, fatigue, dermatitis acneiform, and diarrhea.1
CHARACTERISTICS
* 25%, and a ≥2% difference between treatment arms.1
AE, adverse event; FOLFOX, infusional 5-fluorouracil, leucovorin, and oxaliplatin; KRAS, Kirsten rat sarcoma viral oncogene homologue; mCRC, metastatic colorectal cancer;
NR, not reported in the Vectibix Product Monograph; NRAS, Neuroblastoma RAS viral oncogene homologue; RAS, Rat sarcoma viral oncogene homologue; WT, wild-type.
In patients with WT RAS mCRC receiving Vectibix + FOLFOX vs. FOLFOX alone (n=512):1
| Characteristics | Vectibix + FOLFOX (n=259) | FOLFOX alone (n=253) |
|---|---|---|
| Age | ||
| Mean (years) | 60.5 | 59.8 |
| Range (years) | 27-81 | 24-82 |
| Gender | ||
| Male (n) | 173 | 158 |
| Female (n) | 86 | 95 |
| Ethnicity | ||
| White (%) | 91 | 92 |
| Primary Tumour Type | ||
| Colon (%) | 66 | 65 |
| Rectal (%) | 34 | 35 |
* Baseline disease characteristics were generally balanced between treatment arms.1
- ≥18 years old with previously untreated metastatic adenocarcinoma of the colon or rectum.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–2.
- Prior chemotherapy:
- Fluorouracil-based adjuvant chemotherapy allowed if disease recurrence occurred 6 months after completion.
- Prior oxaliplatin not allowed.
- At least one measurable lesion (≥20 mm).
ECOG, Eastern Cooperative Oncology Group (ECOG); FOLFOX, infusional 5-fluorouracil, leucovorin, and oxaliplatin; mCRC, metastatic colorectal cancer; RAS, Rat sarcoma viral oncogene homologue; WT, wild-type.
- 1183 patients with previously untreated mCRC
- Prospectively analyzed by tumour KRAS (exon 2) status, which was evaluable in 1096 patients (92.6%)
- 512 patients were determined to have wild-type RAS tumours
- A predefined retrospective subset analysis evaluated the treatment effect of Vectibix plus FOLFOX compared with FOLFOX alone in patients with wild-type RAS mCRC
![Patients with previously untreated mCRC (N=1183) were randomized 1:1 to one of two groups: Vectibix Q2W + FOLFOX Q2W (n=593) or FOLFOX Q2W (n=590).1
The primary endpoint was progression-free survival, while secondary endpoints consisted of overall survival, objective response rate, and safety. Duration of treatment was until disease progression, intolerance, or other reason (death, withdrawal, etc). 1
Tumours from the intention to treat (ITT) patient population were prospectively analyzed by tumour mutation status of KRAS (exon 2). In the Vectibix Q2W + FOLFOX Q2W treatment arm, 325 patients had wild-type KRAS, and 221 patients had mutant KRAS. Out of the FOLFOX alone treatment arm, 331 patients had wild-type KRAS tumours, and 219 patients had KRAS mutation on exon 2. 1
Tumours from both treatment arms were further analyzed for biomarker status through additional retrospective analysis for the status of KRAS (exon 3, 4) and NRAS (exon 2, 3, 4). 1
In the Vectibix Q2W + FOLFOX Q2W treatment arm, 259 patients had wild-type RAS and 272 patients had RAS mutations.3 [4A, p6] Out of the FOLFOX alone treatment arm, 253 patients had wild-type RAS tumours and 276 were determined to have RAS mutations.3 The mutation analysis was performed as Vectibix is not indicated for patients with mutant RAS (KRAS/NRAS) or for whom RAS status is unknown.
The dosing administration for FOLFOX Q2W consisted of oxaliplatin 85 mg/m2 and leucovorin 200 mg/m2 (or equivalent) intravenous (IV) infusion followed by fluorouracil 400 mg/m2 IV bolus every 2 weeks on day 1, and fluorouracil 600 mg/m2 22-hour continuous infusions every 2 weeks on days 1 and 2. Vectibix dosing consisted of panitumumab 6 mg/kg IV infusion every 2 weeks on day 1, administered before FOLFOX.2](-/media/themes/amgen/amgencompass-ca/amgencompass-vectibix/images/efficacy/study-prime.png)
![Patients with previously untreated mCRC (N=1183) were randomized 1:1 to one of two groups: Vectibix Q2W + FOLFOX Q2W (n=593) or FOLFOX Q2W (n=590).1
The primary endpoint was progression-free survival, while secondary endpoints consisted of overall survival, objective response rate, and safety. Duration of treatment was until disease progression, intolerance, or other reason (death, withdrawal, etc). 1
Tumours from the intention to treat (ITT) patient population were prospectively analyzed by tumour mutation status of KRAS (exon 2). In the Vectibix Q2W + FOLFOX Q2W treatment arm, 325 patients had wild-type KRAS, and 221 patients had mutant KRAS. Out of the FOLFOX alone treatment arm, 331 patients had wild-type KRAS tumours, and 219 patients had KRAS mutation on exon 2. 1
Tumours from both treatment arms were further analyzed for biomarker status through additional retrospective analysis for the status of KRAS (exon 3, 4) and NRAS (exon 2, 3, 4). 1
In the Vectibix Q2W + FOLFOX Q2W treatment arm, 259 patients had wild-type RAS and 272 patients had RAS mutations.3 [4A, p6] Out of the FOLFOX alone treatment arm, 253 patients had wild-type RAS tumours and 276 were determined to have RAS mutations.3 The mutation analysis was performed as Vectibix is not indicated for patients with mutant RAS (KRAS/NRAS) or for whom RAS status is unknown.
The dosing administration for FOLFOX Q2W consisted of oxaliplatin 85 mg/m2 and leucovorin 200 mg/m2 (or equivalent) intravenous (IV) infusion followed by fluorouracil 400 mg/m2 IV bolus every 2 weeks on day 1, and fluorouracil 600 mg/m2 22-hour continuous infusions every 2 weeks on days 1 and 2. Vectibix dosing consisted of panitumumab 6 mg/kg IV infusion every 2 weeks on day 1, administered before FOLFOX.2](-/media/themes/amgen/amgencompass-ca/amgencompass-vectibix/images/efficacy/study-prime-mobile.png?h=16&thn=1&w=16&hash=0D8777A00685CFE42C14836C47139EF3)
Adapted from the Vectibix Product Monograph,1 Douillard et al.,2 and Douillard et al.3
* Vectibix is not indicated for patients with mutant RAS (KRAS/NRAS) or for whom RAS status is unknown.
FOLFOX, infusional 5-fluorouracil, leucovorin, and oxaliplatin; ITT, intention to treat; IV, intravenous; 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.
