Cited by 415Cancer Genomics and DiagnosticsLung Cancer Treatments and MutationsLung Cancer Diagnosis and Treatment

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Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib

Punnoose, Elizabeth A., Atwal, Siminder, Liu, Weiqun, Raja, Rajiv, Fine, Bernard M., Hughes, Brett G.M., Hicks, Rodney J., Hampton, Garret M., Amler, Lukas C., Pirzkall, Andrea, Lackner, Mark R.·2012·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-11-3148

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Abstract

PURPOSE: Elevated levels or increases in circulating tumor cells (CTC) portend poor prognosis in patients with epithelial cancers. Less is known about CTCs as surrogate endpoints or their use for predictive biomarker evaluation. This study investigated the utility of CTC enumeration and characterization using the CellSearch platform, as well as mutation detection in circulating tumor DNA (ctDNA), in patients with advanced non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Forty-one patients were enrolled in a single-arm phase II clinical trial of erlotinib and pertuzumab. Peripheral blood was analyzed for CTC enumeration, EGFR expression in CTCs, and detection of oncogenic mutations in CTCs and ctDNA. Changes in CTC levels were correlated with 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomographic (FDG-PET) and computed tomographic (CT) imaging and survival endpoints. RESULTS: CTCs were detected (≥ 1 CTC) at baseline in 78% of patients. Greater sensitivity for mutation detection was observed in ctDNA than in CTCs and detected mutations were strongly concordant with mutation status in matched tumor. Higher baseline CTC counts were associated with response to treatment by Response Evaluation Criteria in Solid Tumors (RECIST, P = 0.009) and decreased CTC counts upon treatment were associated with FDG-PET and RECIST response (P = 0.014 and P = 0.019) and longer progression-free survival (P = 0.050). CONCLUSION: These data provide evidence of a correlation between decreases in CTC counts and radiographic response by either FDG-PET or RECIST in patients with advanced NSCLC. These findings require prospective validation but suggest a potential role for using CTC decreases as an early indication of response to therapy and ctDNA for real-time assessment of mutation status from blood.

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Authors: Punnoose, E. A., Atwal, S., Liu, W., Raja, R., Fine, B. M., Hughes, B. G. M., Hicks, R. J., Hampton, G. M., Amler, L. C., Pirzkall, A., & Lackner, M. R.
Affiliations: Genentech (US)
ORCID: Punnoose, Elizabeth A.
Liu, Weiqun
Raja, Rajiv
Fine, Bernard M.
Hughes, Brett G.M.
Hicks, Rodney J.
Lackner, Mark R.
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2012-04-15
Volume: 18
Issue: 8
Pages: 2391-2401
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-11-3148
OpenAlex: W2103077070
Cited by: 415
References: 29
Citations by year: 2026: 2 · 2025: 6 · 2024: 14 · 2023: 26 · 2022: 17 · 2021: 27 · 2020: 33 · 2019: 39 · 2018: 34 · 2017: 56 · 2016: 53 · 2015: 38 · 2014: 38 · 2013: 23 · 2012: 8
FWCI: 11.36
Type: journal article
Language: en
Open access: closed
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords: circulating tumor cells, circulating tumor DNA, non-small cell lung cancer, pertuzumab, erlotinib, EGFR expression, oncogenic mutations, predictive biomarkers, treatment response monitoring, CellSearch, FDG-PET, RECIST, progression-free survival, liquid biopsy
MeSH terms: Erlotinib Hydrochloride, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, DNA, Neoplasm, Female, Genotype, Humans, Lung Neoplasms, Male, Mutation, Neoplastic Cells, Circulating, Quinazolines, Biomarkers, Tumor, Disease-Free Survival, Endpoint Determination, Positron-Emission Tomography, Antibodies, Monoclonal, Humanized, ErbB Receptors

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Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib

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