Open Access Research article

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

Michael L Maitland134*, Matthew R Levine1, Mario E Lacouture27, Kristen E Wroblewski5, Christine H Chung89, Ilyssa O Gordon6, Livia Szeto1, Gail Ratko10, Keyoumars Soltani2, Mark F Kozloff110, Philip C Hoffman1, Ravi Salgia134, David P Carbone9, Theodore G Karrison45 and Everett E Vokes14

Author Affiliations

1 University of Chicago, Section of Hematology/Oncology, 5841 S Maryland Ave, MC 2115, Chicago, IL 60637, USA

2 University of Chicago, Section of Dermatology, 5841 S Maryland Ave, MC 5067, Chicago, IL 60637, USA

3 University of Chicago, Committee on Clinical Pharmacology and Pharmacogenomics, 900 E 57th St, KCBD 6121, Box 11, Chicago, IL 60637, USA

4 University of Chicago, Comprehensive Cancer Center, 5847 S Maryland Ave, MC 1140, Chicago, IL 60637, USA

5 Department of Health Studies, University of Chicago, 5841 S Maryland Ave, MC 2007, Chicago, IL 60637, USA

6 Department of Pathology, University of Chicago, 5841 S Maryland Ave, MC 6101, Chicago, IL, USA

7 Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA

8 Johns Hopkins University, Kimmel Cancer Center, Suite 1100, 401 N Broadway, Baltimore, MD 21287, USA

9 Vanderbilt University Medical Center, 1211 Medical Center Dr, Nashville, TN 37232, USA

10 Ingalls Hospital, One Ingalls Dr, Harvey, IL 60426, USA

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BMC Cancer 2014, 14:5  doi:10.1186/1471-2407-14-5

Published: 4 January 2014

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.

Trial registration

Clinicaltrials.gov Identifier NCT00203931

Keywords:
Pemetrexed; Lung Cancer; Cetuximab; Rash; EGFR; Proteomics