title: Evaluation of a novel rash scale and a serum proteomic predictor in a randomized phase II trial of sequential or concurrent cetuximab and pemetrexed in previously treated non-small cell lung cancer.
abstract: BACKGROUND
  Candidate predictive biomarkers for epidermal growth factor receptor inhibitors (EGFRi), skin rash and serum proteomic assays, require further qualification to improve EGFRi therapy in non-small cell lung cancer (NSCLC). In a phase II trial that was closed to accrual because of changes in clinical practice we examined the relationships among candidate biomarkers, quantitative changes in tumor size, progression-free and overall survival.
  
  
  METHODS
  55 patients with progressive NSCLC after platinum therapy were randomized to receive (Arm A) cetuximab, followed by pemetrexed at progression, or (Arm B) concurrent cetuximab and pemetrexed. All received cetuximab monotherapy for the first 14 days. Pre-treatment serum and weekly rash assessments by standard and EGFRi-induced rash (EIR) scales were collected.
  
  
  RESULTS
  43 patients (20-Arm A, 23-Arm B) completed the 14-day run-in. Median survival was 9.1 months. Arm B had better median overall (Arm B = 10.3 [95% CI 7.5, 16.8]; Arm A = 3.5 [2.8, 11.7] months P = 0.046) and progression-free survival (Arm B = 2.3 [1.6, 3.1]; Arm A = 1.6 [0.9, 1.9] months P = 0.11). The EIR scale distributed ratings among 6 rather than 3 categories but ordinal scale rash severity did not predict outcomes. The serum proteomic classifier and absence of rash after 21 days of cetuximab did.
  
  
  CONCLUSIONS
  Absence of rash after 21 days of cetuximab therapy and the serum proteomic classifier, but not ordinal rash severity, were associated with NSCLC outcomes. Although in a small study, these observations were consistent with results from larger retrospective analyses.
authors.affiliation: University of Chicago, Section of Hematology/Oncology, 5841 S Maryland Ave, MC 2115, Chicago, IL 60637, USA. mmaitlan@medicine.bsd.uchicago.edu.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Maitland
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Levine
authors.forename: Mario E
authors.initials: ME
authors.lastname: Lacouture
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Wroblewski
authors.forename: Christine H
authors.initials: CH
authors.lastname: Chung
authors.forename: Ilyssa O
authors.initials: IO
authors.lastname: Gordon
authors.forename: Livia
authors.initials: L
authors.lastname: Szeto
authors.forename: Gail
authors.initials: G
authors.lastname: Ratko
authors.forename: Keyoumars
authors.initials: K
authors.lastname: Soltani
authors.forename: Mark F
authors.initials: MF
authors.lastname: Kozloff
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hoffman
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
authors.forename: David P
authors.initials: DP
authors.lastname: Carbone
authors.forename: Theodore G
authors.initials: TG
authors.lastname: Karrison
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D000068818:Cetuximab; D002641:Chicago; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005076:Exanthema / Q000097:blood / Q000139:chemically induced*; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D011237:Predictive Value of Tests; D040901:Proteomics / Q000379:methods; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D001798:Blood Proteins; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab