A phase 2 cooperative group adjuvant trial using a biomarker-based decision algorithm in patients with stage i non-small cell lung cancer (SWOG-0720, NCT00792701)

Gerold Bepler, Ralph G. Zinner, James Moon, Royce Calhoun, Kemp Kernstine, Charles C. Williams, Philip C. Mack, Vasco Oliveira, Zhong Zheng, Philip J. Stella, Mary W. Redman, David R. Gandara

Research output: Contribution to journalArticle

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Abstract

BACKGROUND This cooperative group adjuvant phase 2 trial in patients with completely resected stage I non-small cell lung cancer with tumor diameters measuring ≥ 2 cm was designed to assess the feasibility and preliminary efficacy of assigning patients to therapy or observation using a molecularly based decision algorithm. METHODS At least a lobectomy and sampling of recommended mediastinal lymph node stations, good Zubrod performance status, adequate organ function, and a formalin-fixed and paraffin-embedded tumor specimen were required. Excision repair cross-complementing group 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) were analyzed using immunofluorescence-based in situ automated quantitative image analysis and categorized as high or low using prespecified cutoff values. Patients with high ERCC1 and RRM1 were assigned to observation and all others to 4 cycles of cisplatin and gemcitabine. Feasibility was defined as treatment assignment within 84 days from surgery in > 85% of patients. Secondary objectives were to estimate the 2-year survival. RESULTS Treatment assignment met the feasibility criteria in 88% of eligible patients (71 of 81 patients). The collective 2-year disease-free and overall survival rates were 80% and 96%, respectively. Protein levels for RRM1 fell within the previously established range, ERCC1 levels were slightly lower than expected, and they were significantly correlated (correlation coefficient, 0.4). The rates of assignment of patients to observation (22%) and chemotherapy (78%) were as expected. CONCLUSIONS Gene expression analysis for treatment assignment is feasible. Survival results are encouraging and require future validation. Real-time performance of quantitative in situ ERCC1 and RRM1 analysis requires further development.

Original languageEnglish (US)
Pages (from-to)2343-2351
Number of pages9
JournalCancer
Volume120
Issue number15
DOIs
StatePublished - Aug 1 2014

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Non-Small Cell Lung Carcinoma
Biomarkers
Ribonucleotide Reductases
DNA Repair
Observation
gemcitabine
Survival
Therapeutics
Ambulatory Surgical Procedures
Paraffin
Formaldehyde
Cisplatin
Disease-Free Survival
Fluorescent Antibody Technique
Neoplasms
Survival Rate
Lymph Nodes
Gene Expression
Drug Therapy
Proteins

Keywords

  • adjuvant therapy
  • ERCC1 (excision repair cross-complementing group 1)
  • lung cancer
  • personalized medicine
  • RRM1 (ribonucleotide reductase M1)

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

A phase 2 cooperative group adjuvant trial using a biomarker-based decision algorithm in patients with stage i non-small cell lung cancer (SWOG-0720, NCT00792701). / Bepler, Gerold; Zinner, Ralph G.; Moon, James; Calhoun, Royce; Kernstine, Kemp; Williams, Charles C.; Mack, Philip C.; Oliveira, Vasco; Zheng, Zhong; Stella, Philip J.; Redman, Mary W.; Gandara, David R.

In: Cancer, Vol. 120, No. 15, 01.08.2014, p. 2343-2351.

Research output: Contribution to journalArticle

Bepler, G, Zinner, RG, Moon, J, Calhoun, R, Kernstine, K, Williams, CC, Mack, PC, Oliveira, V, Zheng, Z, Stella, PJ, Redman, MW & Gandara, DR 2014, 'A phase 2 cooperative group adjuvant trial using a biomarker-based decision algorithm in patients with stage i non-small cell lung cancer (SWOG-0720, NCT00792701)', Cancer, vol. 120, no. 15, pp. 2343-2351. https://doi.org/10.1002/cncr.28714
Bepler, Gerold ; Zinner, Ralph G. ; Moon, James ; Calhoun, Royce ; Kernstine, Kemp ; Williams, Charles C. ; Mack, Philip C. ; Oliveira, Vasco ; Zheng, Zhong ; Stella, Philip J. ; Redman, Mary W. ; Gandara, David R. / A phase 2 cooperative group adjuvant trial using a biomarker-based decision algorithm in patients with stage i non-small cell lung cancer (SWOG-0720, NCT00792701). In: Cancer. 2014 ; Vol. 120, No. 15. pp. 2343-2351.
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abstract = "BACKGROUND This cooperative group adjuvant phase 2 trial in patients with completely resected stage I non-small cell lung cancer with tumor diameters measuring ≥ 2 cm was designed to assess the feasibility and preliminary efficacy of assigning patients to therapy or observation using a molecularly based decision algorithm. METHODS At least a lobectomy and sampling of recommended mediastinal lymph node stations, good Zubrod performance status, adequate organ function, and a formalin-fixed and paraffin-embedded tumor specimen were required. Excision repair cross-complementing group 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) were analyzed using immunofluorescence-based in situ automated quantitative image analysis and categorized as high or low using prespecified cutoff values. Patients with high ERCC1 and RRM1 were assigned to observation and all others to 4 cycles of cisplatin and gemcitabine. Feasibility was defined as treatment assignment within 84 days from surgery in > 85{\%} of patients. Secondary objectives were to estimate the 2-year survival. RESULTS Treatment assignment met the feasibility criteria in 88{\%} of eligible patients (71 of 81 patients). The collective 2-year disease-free and overall survival rates were 80{\%} and 96{\%}, respectively. Protein levels for RRM1 fell within the previously established range, ERCC1 levels were slightly lower than expected, and they were significantly correlated (correlation coefficient, 0.4). The rates of assignment of patients to observation (22{\%}) and chemotherapy (78{\%}) were as expected. CONCLUSIONS Gene expression analysis for treatment assignment is feasible. Survival results are encouraging and require future validation. Real-time performance of quantitative in situ ERCC1 and RRM1 analysis requires further development.",
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T1 - A phase 2 cooperative group adjuvant trial using a biomarker-based decision algorithm in patients with stage i non-small cell lung cancer (SWOG-0720, NCT00792701)

AU - Bepler, Gerold

AU - Zinner, Ralph G.

AU - Moon, James

AU - Calhoun, Royce

AU - Kernstine, Kemp

AU - Williams, Charles C.

AU - Mack, Philip C.

AU - Oliveira, Vasco

AU - Zheng, Zhong

AU - Stella, Philip J.

AU - Redman, Mary W.

AU - Gandara, David R.

PY - 2014/8/1

Y1 - 2014/8/1

N2 - BACKGROUND This cooperative group adjuvant phase 2 trial in patients with completely resected stage I non-small cell lung cancer with tumor diameters measuring ≥ 2 cm was designed to assess the feasibility and preliminary efficacy of assigning patients to therapy or observation using a molecularly based decision algorithm. METHODS At least a lobectomy and sampling of recommended mediastinal lymph node stations, good Zubrod performance status, adequate organ function, and a formalin-fixed and paraffin-embedded tumor specimen were required. Excision repair cross-complementing group 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) were analyzed using immunofluorescence-based in situ automated quantitative image analysis and categorized as high or low using prespecified cutoff values. Patients with high ERCC1 and RRM1 were assigned to observation and all others to 4 cycles of cisplatin and gemcitabine. Feasibility was defined as treatment assignment within 84 days from surgery in > 85% of patients. Secondary objectives were to estimate the 2-year survival. RESULTS Treatment assignment met the feasibility criteria in 88% of eligible patients (71 of 81 patients). The collective 2-year disease-free and overall survival rates were 80% and 96%, respectively. Protein levels for RRM1 fell within the previously established range, ERCC1 levels were slightly lower than expected, and they were significantly correlated (correlation coefficient, 0.4). The rates of assignment of patients to observation (22%) and chemotherapy (78%) were as expected. CONCLUSIONS Gene expression analysis for treatment assignment is feasible. Survival results are encouraging and require future validation. Real-time performance of quantitative in situ ERCC1 and RRM1 analysis requires further development.

AB - BACKGROUND This cooperative group adjuvant phase 2 trial in patients with completely resected stage I non-small cell lung cancer with tumor diameters measuring ≥ 2 cm was designed to assess the feasibility and preliminary efficacy of assigning patients to therapy or observation using a molecularly based decision algorithm. METHODS At least a lobectomy and sampling of recommended mediastinal lymph node stations, good Zubrod performance status, adequate organ function, and a formalin-fixed and paraffin-embedded tumor specimen were required. Excision repair cross-complementing group 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) were analyzed using immunofluorescence-based in situ automated quantitative image analysis and categorized as high or low using prespecified cutoff values. Patients with high ERCC1 and RRM1 were assigned to observation and all others to 4 cycles of cisplatin and gemcitabine. Feasibility was defined as treatment assignment within 84 days from surgery in > 85% of patients. Secondary objectives were to estimate the 2-year survival. RESULTS Treatment assignment met the feasibility criteria in 88% of eligible patients (71 of 81 patients). The collective 2-year disease-free and overall survival rates were 80% and 96%, respectively. Protein levels for RRM1 fell within the previously established range, ERCC1 levels were slightly lower than expected, and they were significantly correlated (correlation coefficient, 0.4). The rates of assignment of patients to observation (22%) and chemotherapy (78%) were as expected. CONCLUSIONS Gene expression analysis for treatment assignment is feasible. Survival results are encouraging and require future validation. Real-time performance of quantitative in situ ERCC1 and RRM1 analysis requires further development.

KW - adjuvant therapy

KW - ERCC1 (excision repair cross-complementing group 1)

KW - lung cancer

KW - personalized medicine

KW - RRM1 (ribonucleotide reductase M1)

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