Management of skin toxicities during panitumumab treatment in metastatic colorectal cancer

Table 1 Demographic data (primary analysis set, n = 229)

	n	Results
Male gender, n (%)	229	132 (57.6)
Age (yr)	229
Mean (SD)	229	66.2 (11.5)
≥ 75, n (%)	229	68 (29.7)
Cancer other than metastatic colorectal cancer, n (%)	228	20 (8.8)
Duration since diagnosis of primary disease (yr), mean (SD)	226	2.9 (2.3)
Duration since diagnosis of metastatic disease (yr), mean (SD)	227	2.0 (1.5)
Metastatic sites, n (%)
Liver	229	170 (74.2)
Lung	229	92 (40.2)
Peritoneum	229	38 (16.6)
Lymph nodes	229	59 (25.8)
Bone	229	10 (4.4)
Other	229	29 (12.7)
BRAF genotyping performed, n (%)	225	70 (31.1)
If performed, BRAF genotyping
Non-mutated BRAF	70	62 (88.6)
Mutated BRAF	70	5 (7.1)
BRAF not assessable	70	3 (4.3)
Previous radiotherapy treatment (any cancer), n (%)	227	62 (27.3)
Previous adjuvant chemotherapya, n (%)	227	101 (44.5)
Previous chemotherapy for metastatic diseaseb, n (%)	229	207 (90.4)
Total treatment duration, weeks, mean (SD)
Line 1	207	26.3 (21.9)
Line 2	165	23.0 (20.5)
Line 3	97	19.9 (17.1)
Line 4	24	19.9 (17.6)
Previous radiotherapy for metastatic disease, n (%)		30 (13.1)
Abdominal lymph nodes	218	5 (26.3)
Pelvic	221	10 (45.5)
Other	221	18 (81.8)

^aMost frequent chemotherapy protocols (n = 99): LV5FU2/oxaliplatin FOLFOX (n = 42, 42.4%). FOLFIRI/bevacizumab (n = 9, 9.1%), LV5FU2 (n = 6, 6.1%), FOLFOX/bevacizumab (n = 5, 5.1%);

^bMost frequent chemotherapy protocols for lines 1 to 4, respectively: LV5FU2/oxaliplatin FOLFOX (22.2%, 13.3%, 8.2%, 16.7%), FOLFIRI/bevacizumab (28.0%, 18.2%, 23.7%, 0%); for lines 5 to 8 (n = 11, 6, 3,1): LV5FU2/oxaliplatin (27.3%, 0%, 33.3%, 0%). BRAF: Serine/threonine-protein kinase B-Raf; FOLFIRI: Folinic acid, fluorouracil and irinotecan; FOLFOX: Folinic acid, fluorouracil and oxaliplatin.

Table 2 Primary endpoint: dermatological toxicities (primary analysis set, n = 229)

	Day 15 (n = 214)	Month 1 (n = 208)	Month 2 (n = 186)	Month 3 (n = 153)	Month 4 (n = 122)	Month 5 (n = 93)	Month 6 (n = 87)
At least one dermatological toxicity, n (%)	127 (59.3)	141 (67.8)	139 (74.7)	107 (69.9)	76 (63.3)	52 (57.1)	40 (46.5)
Dermatological toxicities
Rash/acneiform rash, n (%)	111 (51.9)	123 (59.1)	110 (59.1)	85 (55.6)	56 (45.9)	41 (44.1)	34 (39.1)
Grade 1-2	101 (47.2)	115 (55.3)	99 (53.2)	82 (53.6)	51 (41.8)	39 (41.9)	33 (37.9)
Grade 3-4	10 (4.7)	7 (3.4)	8 (4.3)	2 (1.1)	4 (3.2)	1 (1.1)	1 (1.1)
Grade missing	0	1	3	1	1	1	0
Skin cracks, n (%)	5 (2.3)	17 (8.2)	35 (18.8)	34 (22.2)	23 (18.9)	20 (21.5)	17 (19.5)
Grade 1-2	4 (1.9)	16 (7.7)	32 (17.2)	33 (21.6)	22 (18.0)	19 (20.4)	17 (19.8)
Grade 3-4	1 (0.5)	1 (0.5)	3 (1.6)	1 (0.6)	1 (0.8)	0	0
Grade missing	0	0	0	0	0	1	0
Paronychia/Perionyxis, n (%)	6 (2.8)	11 (5.3)	22 (11.8)	15 (9.8)	12 (9.8)	9 (9.7)	5 (5.7)
Grade 1-2	6 (2.8)	10 (4.8)	21 (11.3)	15 (9.8)	12 (9.8)	8 (8.6)	5 (5.7)
Grade 3-4	0	1 (0.5)	1 (0.5)	0	0	1 (1.1)	0
Xerosis, n (%)	27 (12.6)	36 (17.3)	53 (28.5)	44 (28.8)	22 (18.0)	15 (16.1)	11 (12.6)
Grade 1-2	27 (12.6)	34 (16.3)	51 (27.4)	43 (28.1)	21 (17.2)	15 (16.1)	11 (12.6)
Grade 3-4	0	2 (1.0)	2 (1.1)	0	1 (0.8)	0	0
Grade missing	0	0	0	1	0	0	0
Mucositis, n (%)	12 (5.6)	15 (7.2)	19 (10.2)	8 (5.2)	3 (2.5)	3 (3.2)	2 (2.3)
Grade 1-2	12 (5.6)	15 (7.2)	18 (9.7)	8 (5.2)	3 (2.5)	3 (3.2)	2 (2.3)
Grade 3-4	0	0	1 (0.5)	0	0	0	0
Hypertrichosis, n (%)	1 (0.5)	4 (1.9)	5 (2.7)	7 (4.6)	7 (5.7)	2 (2.2)	2 (2.3)
Grade 1-2	1 (0.5)	4 (1.9)	5 (2.7)	7 (4.6)	7 (5.7)	2 (2.2)	2 (2.3)
Other, n (%)	5 (2.3)	5 (2.4)	4 (2.2)	4 (2.6)	3 (2.5)	0	1 (1.1)
Grade 1-2	5 (2.3)	5 (2.4)	4 (2.2)	4 (2.6)	3 (2.5)	0	1 (1.1)

Table 3 Doses delayed and dose adjustment (decrease) in patients with rash/acneiform rash according to the toxicity grades (Primary analysis set, n = 229)

	Day 15 (n = 214)	Month 1 (n = 208)	Month 2 (n = 186)	Month 3 (n = 153)	Month 4 (n = 122)	Month 5 (n = 93)	Month 6 (n = 87)
Rash/acneiform rash, grade 1-2, n	101	115	99	82	51	39	33
Doses delayed, n (%)	2 (2.0)	4 (3.5)	13 (13.1)	21 (25.9)	4 (7.8)	4 (10.3)	9 (27.3)
MD	0	0	0	1	0	0	0
Dose adjustment, n (%)	0	7 (6.3)	3 (3.3)	13 (16.9)	12 (25.5)	8 (20.5)	6 (18.2)
MD	1	3	8	5	4	0	3
Rash/acneiform rash, grade 3-4, n	10	7	8	2	4	1	1
Doses delayed, n (%)	1 (10.0)	1 (14.3)	4 (50.0)	2 (100)	1 (25.0)	0	0
MD	0	0	0	0	0	0	0
Dose adjustment, n (%)	2 (25.0)	0	2 (33.3)	2 (100)	1 (25.0)	0	0
MD	2	2	2	0	0	0	1

MD: Missing data.

Table 4 Preventive treatments for dermatological toxicities (Primary analysis set, n = 229)

	n = 229
At least one preventive treatment, n (%)	151/229 (65.9)
Emollients	114/151 (75.5)
Oral antibiotics	127/151 (84.1)
Emollients and oral antibiotics	95/151 (62.9)
Sunscreen	9/150 (6.0)
Topical corticosteroids	14/151 (9.3)
Other (including topical antibiotics)	33/151 (21.9)
Topical antibiotics	30/33 (90.9)

Table 5 Curative treatments for dermatological toxicities (Primary analysis set, n = 229)

	Day 15 (n = 214)	Month 1 (n = 208)	Month 2 (n = 186)	Month 3 (n = 153)	Month 4 (n = 122)	Month 5 (n = 93)	Month 6 (n = 87)
At least one curative treatment, n (%)	117/214 (54.7)	124/208 (59.6)	118/186 (63.4)	92/153 (60.1)	63/120 (52.5)	47/92 (51.1)	39/87 (44.8)
Emollients	74 (63.2)	82 (66.1)	84 (71.2)	69 (75.0)	45 (71.4)	29 (61.7)	24 (61.5)
Oral antibiotics	88 (75.2)	90 (72.6)	88 (74.6)	65 (70.7)	43 (68.3)	31 (66.0)	28 (71.8)
Emollients and oral antibiotics	60 (51.3)	61 (49.2)	61 (51.7)	47 (51.1)	28 (44.4)	17 (36.2)	16 (41.0)
Antiseptics	9 (7.8)	7 (5.6)	11 (9.3)	7 (7.6)	2 (3.2)	1 (2.1)	0 (0.0)
Antihistamines	12 (10.3)	10 (8.1)	11 (9.4)	10 (10.9)	6 (9.5)	5 (10.6)	2 (5.1)
Corticosteroids	19 (16.2)	26 (21.0)	23 (19.5)	19 (20.7)	12 (19.0)	6 (12.8)	9 (23.1)
Other (including topical antibiotics)	51 (44.0)	47 (37.9)	35 (29.7)	29 (31.9)	20 (31.7)	16 (34.0)	13 (33.3)
Topical antibiotics	48 (94.1)	43 (91.5)	30 (85.7)	25 (86.2)	18 (90.0)	16 (100)	13 (100)