The identification of patient (pt) characteristics associated with dermatologic toxicity severity during treatment with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies could inform treatment choices for patients with metastatic colorectal cancer.
Data from the randomized, first-line, phase 3 PRIME trial of pmab + FOLFOX vs FOLFOX and the randomized, second-line, phase 3 20050181 trial of pmab + FOLFIRI vs FOLFIRI were analyzed to evaluate the association of dermatologic toxicity severity with pt characteristics/laboratory values and treatment outcomes. This study was supported by Amgen Inc.
In the pmab arms from 20050181 and PRIME, pts with grade 2–4 dermatologic toxicity consistently had a trend of lower neutrophil-to-lymphocyte ratio (NLR) vs those with grade 0–1 at baseline, weeks 2–3, 4–5, 6–7, and 8–9 (Table; baseline, week 8–9 shown). Carcinoembryonic antigen was elevated in pts with grade 0–1 dermatologic toxicity in the pmab + FOLFOX group but reduced in grade 0–1 pts in the pmab + FOLFIRI group when each was compared with grade 2–4 dermatologic toxicity pts (Table). Among pts with progression-free survival ≥28 days, those with grade 2–4 dermatologic toxicity had improved overall survival and progression-free survival compared with pts with grade 0–1 toxicity (Table).
This study did not clearly identify pt characteristics that are potential dermatologic toxicity biomarkers; further studies are required to understand the relationship between NLR and dermatologic toxicity severity. Increased dermatologic toxicity severity was associated with improved clinical outcomes.
|Panitumumab + FOLFIRI||Panitumumab + FOLFOX|
|Grade 0–1||Grade 2–4||Grade 0–1||Grade 2–4|
|Patient Characteristics, n||57||150||55||201|
|Baseline NLR, median (IQR)*||3.7 (2.8–5.3)||3.1 (2.2–4.8)||4.2 (2.9–6.4)||3.1 (2.3–4.5)|
|Week 8–9 NLR, median (IQR)*||2.9 (1.5–3.7)||2.0 (1.4–3.1)||2.1 (1.4–3.1)||1.9 (1.2–2.9)|
|Basline BSA (m2), mean||1.7||1.9||1.9||1.8|
|Baseline ECOG performance status 0, %||26||58||44||64|
|Baseline ECOG performance status 1, %||67||37||42||32|
|Baseline CEA (µg/L), mean||220.0||422.4||848.7||466.4|
|Alkaline phosphatase†(U/L), mean (n)||226.0 (32)||190.4 (106)||255.3 (28)||147.2 (157)|
|Uric acid† (µmol/L), mean (n)||244.9 (29)||253.5 (94)||323.3 (28)||219.6 (137)|
|Uric acid change from baseline† (µmol/L), mean (n)||–34.1||–72.5||–1.4||–72.1|
|Creatinine† (µmol/L), mean (n)||70.0 (32)||73.5 (105)||71.6 (29)||68.1 (162)|
|Patients with narcotic concomitant medications, n (%)||25 (44)||73 (49)||33 (60)||101 (50)|
|White blood cell count† (109/L), mean (n)||5.5 (34)||5.9 (107)||7.9 (29)||6.1 (165)|
|Patients with NSAID concomitant medications, n (%)||16 (28)||52 (35)||27 (49)||71 (35)|
|Efficacy Outcomes, n||53||148||52||199|
|Overall survival (months), median (95% CI)||10.7 (7.8–14.5)||19.4 (16.0–21.3)||15.4 (9.4–23.6)||28.7 (25.4–NE)|
|Hazard ratio (95% CI)||0.51 (0.35–0.74)||0.45 (0.30–0.66)|
|Progression-free survival (months), median (95% CI)||3.9 (3.5–8.6)||8.4 (7.4–9.5)||7.2 (5.3–11.0)||11.3 (9.6–12.6)|
|Hazard ratio (95% CI)||0.83 (0.59–1.17)||0.64 (0.46–0.89)|
BSA, body surface area; CEA, carcinoembryonic antigen; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; IQR, interquartile range; NLR, neutrophil-to-lymphocyte ratio; NSAID, nonsteroidal anti-inflammatory drug; NE = not estimable. *From pooled local site data, platform counting bias should be considered. †Laboratory values within 7 days of worst skin toxicity.
Clinical trial identification
Legal entity responsible for the study
T.J. Price: Served as a consultant for Amgen Inc. and Merck. J-Y. Douillard: Received honoraria and travel expenses from, and served as a consultant for, Amgen Inc., Bayer, Merck and Roche Pharma AG, and received research funding from Merck Serono. X. Guan, C. Bohac: Employee of, and owns stock in, Amgen Inc. M. Peeters: Received honoraria, research funding, and travel expenses from Amgen Inc., and has served as a consultant and on speakers bureau for Amgen Inc.
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