531P - Associations between dermatologic toxicity severity, patient characteristics, and efficacy among patients treated with panitumumab (Pmab) and chemo...

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Gastrointestinal Cancers
Presenter Timothy Price
Citation Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370
Authors T.J. Price1, J. Douillard2, X. Guan3, C. Bohac4, M. Peeters5
  • 1Medical Oncology, Queen Elizabeth Hospital, 5011 - Adelaide/AU
  • 2Medical Oncology, ICO René Gauducheau, Nantes/FR
  • 3Biostatistics, Amgen Inc., Thousand Oaks/US
  • 4Clinical Research, Amgen Inc., Thousand Oaks/US
  • 5Oncology, Antwerp University Hospital, Edegem/BE

Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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)
P value 0.064 0.001
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)
P value 0.124 0.441
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

NCT00364013; NCT00339183

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

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.