Introduction
Methods
Study designs and patients
Skin toxicity
QoL endpoints and analyses
Primary analysis
Secondary analyses
Results
Patients
PRIME | 181 | 408 | ||||
---|---|---|---|---|---|---|
Panitumumab + FOLFOX4 (n = 232) | FOLFOX4 (n = 224) | Panitumumab + FOLFIRI (n = 187) | FOLFIRI (n = 194) | Panitumumab + BSC (n = 66) | BSC (n = 48) | |
Sex | ||||||
Male | 153 (66) | 145 (65) | 120 (64) | 126 (65) | 42 (64) | 32 (67) |
Female | 79 (34) | 79 (35) | 67 (36) | 68 (35) | 24 (36) | 16 (33) |
Age (years), median (range) | 61.0 (27.0, 81.0) | 61.0 (24.0, 82.0) | 60.0 (28.0, 81.0) | 60.5 (33.0, 85.0) | 61.5 (29.0, 79.0) | 62.5 (32.0, 81.0) |
Age group, n (%) (years) | ||||||
<65 | 151 (65) | 143 (64) | 116 (62) | 125 (64) | 37 (56) | 29 (60) |
≥65 | 81 (35) | 81 (36) | 71 (38) | 69 (36) | 29 (44) | 19 (40) |
<75 | 213 (92) | 201 (90) | 178 (95) | 182 (94) | 57 (86) | 42 (88) |
≥75 | 19 (8) | 23 (10) | 9 (5) | 12 (6) | 9 (14) | 6 (13) |
ECOG performance score, n (%) | ||||||
0 or 1 | 221 (95) | 209 (93) | 180 (96) | 184 (95) | 60 (91) | 41 (85) |
2 | 11 (5) | 15 (7) | 7 (4) | 10 (5) | 6 (9) | 7 (15) |
Primary tumour diagnosis, n (%) | ||||||
Colon | 151 (65) | 148 (66) | 107 (57) | 135 (70) | 45 (68) | 32 (67) |
Rectum | 81 (35) | 76 (34) | 80 (43) | 59 (30) | 21 (32) | 16 (33) |
Site of metastases, n (%) | N/A | N/A | ||||
Liver only | 47 (20) | 34 (15) | 34 (18) | 47 (24) | ||
Liver + other | 152 (66) | 153 (68) | 127 (68) | 119 (61) | ||
Other only | 33 (14) | 37 (17) | 26 (14) | 28 (14) | ||
Number of metastases, n (%) | N/A | N/A | ||||
1 | 55 (24) | 41 (18) | 38 (20) | 53 (27) | ||
2 | 80 (34) | 84 (38) | 70 (37) | 57 (29) | ||
3+ | 97 (42) | 99 (44) | 79 (42) | 83 (43) | ||
Missing | 0 (0) | 0 (0) | 0 (0) | 1 (<1) | ||
Median EuroQoL score (range) | ||||||
Health state index | 0.80 (−0.48, 1.00)a
| 0.80 (−0.01, 1.00)c
| 0.80 (−0.18, 1.00)e
| 0.80 (−0.18, 1.00) | 0.78 (−0.07, 1.00)h
| 0.73 (0.09, 1.00)j
|
Overall health rating | 78.0 (0.0, 100.0)b
| 70.0 (6.0, 100.0)d
| 75.0 (20.0, 100.0)f
| 75.0 (20.00, 100.0)g
| 70.5 (29.0, 97.0)i
| 60.0 (9.0, 93.0)j
|
Quality of life
PRIME | 181 | 408 | ||||
---|---|---|---|---|---|---|
Panitumumab + FOLFOX4 | FOLFOX4 | Panitumumab + FOLFIRI | FOLFIRI | Panitumumab + BSC | BSC | |
(a)
| ||||||
Health state index |
n = 224 |
n = 221 |
n = 186 |
n = 194 |
n = 61 |
n = 45 |
Adjusted LS mean | −0.005 | 0.006 | −0.028 | 0.017 | −0.003 | 0.108 |
95 % confidence intervals | −0.027, 0.017 | −0.022, 0.034 | −0.052, −0.004 | −0.049, 0.014 | −0.076, 0.070 | −0.103, 0.319 |
Difference | −0.011 (−0.042, 0.020) | −0.011 (−0.047, 0.025) | −0.111 (−0.323, 0.101) | |||
p value | 0.50 | 0.56 | 0.30 | |||
Overall health rating |
n = 222 |
n = 218 |
n = 182 |
n = 190 |
n = 59 |
n = 45 |
Adjusted LS mean | −0.91 | 0.73 | −1.19 | −0.73 | −0.28 | −0.59 |
95 % confidence intervals | −2.77, 0.96 | −1.67, 3.14 | −2.90, 0.51 | −2.89, 1.43 | −4.08, 3.51 | −6.35, 5.16 |
Difference | −1.64 (−4.26, 0.98) | −0.47 (−2.85, 1.92) | 0.31 (−4.54, 5.15) | |||
p value | 0.22 | 0.70 | 0.90 | |||
(b)
| ||||||
Health state index |
n = 224 |
n = 221 |
n = 186 |
n = 194 |
n = 61 |
n = 44 |
Adjusted LS mean | 0.021 | 0.041 | −0.027 | −0.016 | −0.048 | 0.175 |
95 % confidence intervals | −0.014, 0.057 | 0.003, 0.079 | −0.085, 0.032 | −0.076, 0.044 | −0.116, 0.019 | −0.039, 0.388 |
Difference | −0.019 (−0.050, 0.012) | −0.011 (−0.047, 0.026) | −0.223 (−0.457, 0.010) | |||
p value | 0.22 | 0.57 | 0.06 | |||
Overall health rating |
n = 222 |
n = 218 |
n = 182 |
n = 190 |
n = 59 |
n = 44 |
Adjusted LS mean | −1.65 | 0.40 | −0.74 | −0.48 | −3.29 | 1.24 |
95 % confidence intervals | −4.25, 0.95 | −2.36, 3.16 | −4.58, 3.11 | −4.41, 3.45 | −7.18, 0.59 | −7.00, 9.49 |
Difference | −2.05 (−4.59, 0.49) | −0.26 (−2.72, 2.20) | −4.54 (−14.60, 5.53) | |||
p value | 0.11 | 0.84 | 0.38 |
Skin toxicity
Skin toxicity (MedDRA preferred term), n (%) | PRIME | 181 | 408 | |||
---|---|---|---|---|---|---|
Panitumumab + FOLFOX4 (n = 232) | FOLFOX4 (n = 224) | Panitumumab + FOLFIRI (n = 187) | FOLFIRI (n = 194) | Panitumumab + BSC (n = 65) | BSC (n = 48) | |
(a)
| ||||||
Rash | 131 (56) | 17 (8) | 105 (56) | 17 (9) | 12 (18) | 1 (2) |
Dermatitis acneiform | 83 (36) | 0 | 55 (29) | 2 (1) | 45 (69) | 0 (0) |
Pruritus | 63 (27) | 11 (5) | 40 (21) | 8 (4) | 51 (78) | 2 (4) |
Dry skin | 56 (24) | 9 (4) | 40 (21) | 11 (6) | 10 (15) | 0 (0) |
Skin fissures | 43 (19) | 1 (<1) | 38 (20) | 1 (1) | 22 (34) | 0 (0) |
Erythema | 42 (18) | 8 (4) | 27 (14) | 6 (3) | 49 (75) | 1 (2) |
Acne | 36 (16) | 1 (<1) | 29 (16) | 4 (2) | 13 (20) | 0 (0) |
Palmar–plantar erythrodysaesthesia syndrome | 24 (10) | 7 (3) | 20 (11) | 10 (5) | 1 (2) | 0 (0) |
Exfoliative rash | 7 (3) | 3 (1) | 6 (3) | 0 (0) | 20 (31) | 0 (0) |
Skin toxicity (MedDRA preferred term), n (%) | PRIME | 181 | ||
---|---|---|---|---|
Panitumumab + FOLFOX4 | FOLFOX4 | Panitumumab + FOLFIRI | FOLFIRI | |
(b)
| ||||
Rash | 10 (4) | 0 (0) | 6 (3) | 0 (0) |
Dermatitis acneiform | 4 (2) | 0 (0) | 0 (0) | 0 (0) |
Acne | 1 (1) | 0 (0) | 2 (1) | 0 (0) |
Analysis of quality of life by skin toxicity
PRIME Worst skin toxicity grade | 181 Worst skin toxicity grade | 408 Worst skin toxicity grade | ||||
---|---|---|---|---|---|---|
<3 | ≥3 | <3 | ≥3 | <3 | ≥3 | |
Health state index |
n = 351 |
n = 94 |
n = 299 |
n = 81 |
n = 95 |
n = 11 |
Adjusted LS mean | 0.007 | −0.006 | −0.024 | −0.022 | 0.029 | 0.076 |
95 % confidence intervals | −0.012, 0.025 | −0.040, 0.029 | −0.044, −0.004 | −0.059, 0.016 | −0.077, 0.135 | −0.078, 0.229 |
Difference | 0.0123 (−0.026, 0.050) | −0.003 (−0.046, 0.041) | −0.047 (−0.170, 0.076) | |||
p value | 0.52 | 0.91 | 0.45 | |||
Overall health rating |
n = 348 |
n = 92 |
n = 294 |
n = 78 |
n = 93 |
n = 11 |
Adjusted LS mean | −0.02 | −0.15 | −1.33 | −0.59 | −3.08 | 2.21 |
95 % confidence intervals | −1.61, 1.56 | −3.03, 2.74 | −2.78, 0.11 | −3.20, 2.03 | −6.27, 0.10 | −4.87, 9.29 |
Difference | 0.13 (−3.03, 3.29) | −0.75 (−3.65, 2.15) | −5.29 (−12.3, 1.71) | |||
p value | 0.94 | 0.61 | 0.14 |
Worst skin toxicity grade | ||||
---|---|---|---|---|
<3 | ≥3 | |||
Panitumumab + FOLFOX4 | FOLFOX4 | Panitumumab + FOLFOX4 | FOLFOX4 | |
(a)
| ||||
Health state index |
n = 136 |
n = 215 |
n = 88 |
n = 6 |
Adjusted LS mean | −0.003 | 0.011 | −0.004 | 0.009 |
95 % confidence intervals | −0.033, 0.027 | −0.014, 0.036 | −0.040, 0.032 | −0.116, 0.134 |
Difference | −0.015 (−0.053, 0.024) | −0.013 (−0.140, 0.114) | ||
Overall health rating |
n = 136 |
n = 212 |
n = 86 |
n = 6 |
Adjusted LS mean | −0.30 | 0.66 | −1.56 | 2.10 |
95 % confidence intervals | −2.83, 2.23 | −1.46, 2.78 | −4.66, 1.54 | −8.36, 12.57 |
Difference | −0.96 (−4.23, 2.32) | −3.66 (−14.30, 6.98) |
Worst skin toxicity grade | ||||
---|---|---|---|---|
<3 | ≥3 | |||
Panitumumab + FOLFIRI | FOLFIRI | Panitumumab + FOLFIRI | FOLFIRI | |
(b)
| ||||
Health state index |
n = 111 |
n = 188 |
n = 75 |
n = 6 |
Adjusted LS mean | −0.019 | −0.022 | −0.038 | 0.032 |
95 % confidence intervals | −0.051, 0.014 | −0.047, 0.004 | −0.074, −0.001 | −0.100, 0.164 |
Difference | 0.003 (−0.038, 0.044) | −0.070 (−0.206, 0.066) | ||
Overall health rating |
n = 110 |
n = 184 |
n = 72 |
n = 6 |
Adjusted LS mean | −2.10 | −0.61 | −1.39 | 6.82 |
95 % confidence intervals | −4.47, 0.26 | −2.53, 1.32 | −4.15, 1.38 | −2.04, 15.68 |
Difference | −1.50 (−4.53, 1.53) | −8.21 (−17.26, 0.85) |
Worst skin toxicity grade | ||||
---|---|---|---|---|
<3 | ≥3 | |||
Panitumumab + BSC | BSC | Panitumumab + BSC | BSC | |
(c)
| ||||
Health state index |
n = 50 |
n = 45 |
n = 11 |
n = 0 |
Adjusted LS mean | −0.027 | 0.084 | 0.026 | − |
95 % confidence intervals | −0.096, 0.042 | −0.122, 0.291 | −0.146, 0.199 | − |
Difference | −0.112 (−0.329, 0.106) | − | ||
Overall health rating |
n = 48 |
n = 45 |
n = 11 |
n = 0 |
Adjusted LS mean | −2.47 | −3.08 | 3.54 | − |
95 % confidence intervals | −5.72, 0.77 | −14.57, 8.41 | −3.51, 10.59 | − |
Difference | 0.60 (−11.36, 12.57) | − |