Phase II selection design trial of concurrent chemotherapy and cetuximab versus chemotherapy followed by cetuximab in advanced-stage non-small-cell lung cancer

Southwest Oncology Group study S0342

Roy S. Herbst, Karen Kelly, Kari Chansky, Philip Mack, Wilbur A. Franklin, Fred R. Hirsch, James N. Atkins, Shaker R. Dakhil, Kathy S. Albain, Edward S. Kim, Mary Redman, John J. Crowley, David R Gandara

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Purpose: Randomized clinical trials failed to show a survival benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus concurrent chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC), with preclinical data suggesting potential negative interactions. In contrast, pilot trials of the EGFR-targeted antibody, cetuximab, plus chemotherapy suggested enhanced antitumor activity. This randomized phase II trial was designed to select a cetuximab plus chemotherapy regimen for phase III evaluation. Patients and Methods: Treatment-naive patients with advanced-stage NSCLC were randomly assigned to receive paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6) every 3 weeks plus concurrent cetuximab (400 mg/m2 loading dose followed by 250 mg/m2 weekly) for four cycles followed by maintenance cetuximab or sequential paclitaxel- carboplatin for four cycles followed by cetuximab. Results: Of 242 patients enrolled, 224 were eligible and assessable for response (106 and 118 patients in the concurrent and sequential arms, respectively). With a median follow-up time of 32 months, the median overall survival was 10.9 months (95% CI, 9.2 to 13.0 months) for patients receiving concurrent therapy and 10.7 months (95% CI, 8.5 to 12.8 months) for patients receiving sequential therapy (P = .57); 1-year survival rates were 45% (95% CI, 36% to 54%) and 44% (95% CI, 35% to 53%), respectively. Response rates and progression-free survival times were similar in both arms, as was grade 3 rash, whereas sensory neuropathy was higher in the concurrent arm (15% v5%in the sequential arm; P = .036). Conclusion: Although both regimens met the efficacy criterion for continued evaluation, the concurrent regimen of paclitaxel/carboplatin plus cetuximab was chosen.

Original languageEnglish (US)
Pages (from-to)4747-4754
Number of pages8
JournalJournal of Clinical Oncology
Volume28
Issue number31
DOIs
StatePublished - Nov 1 2010

Fingerprint

Non-Small Cell Lung Carcinoma
Drug Therapy
Carboplatin
Paclitaxel
Epidermal Growth Factor Receptor
Survival
Cetuximab
Exanthema
Protein-Tyrosine Kinases
Disease-Free Survival
Area Under Curve
Therapeutics
Survival Rate
Randomized Controlled Trials
Maintenance
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Phase II selection design trial of concurrent chemotherapy and cetuximab versus chemotherapy followed by cetuximab in advanced-stage non-small-cell lung cancer : Southwest Oncology Group study S0342. / Herbst, Roy S.; Kelly, Karen; Chansky, Kari; Mack, Philip; Franklin, Wilbur A.; Hirsch, Fred R.; Atkins, James N.; Dakhil, Shaker R.; Albain, Kathy S.; Kim, Edward S.; Redman, Mary; Crowley, John J.; Gandara, David R.

In: Journal of Clinical Oncology, Vol. 28, No. 31, 01.11.2010, p. 4747-4754.

Research output: Contribution to journalArticle

Herbst, Roy S. ; Kelly, Karen ; Chansky, Kari ; Mack, Philip ; Franklin, Wilbur A. ; Hirsch, Fred R. ; Atkins, James N. ; Dakhil, Shaker R. ; Albain, Kathy S. ; Kim, Edward S. ; Redman, Mary ; Crowley, John J. ; Gandara, David R. / Phase II selection design trial of concurrent chemotherapy and cetuximab versus chemotherapy followed by cetuximab in advanced-stage non-small-cell lung cancer : Southwest Oncology Group study S0342. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 31. pp. 4747-4754.
@article{b61fc0f9d02744a2b6d1f824f37bb564,
title = "Phase II selection design trial of concurrent chemotherapy and cetuximab versus chemotherapy followed by cetuximab in advanced-stage non-small-cell lung cancer: Southwest Oncology Group study S0342",
abstract = "Purpose: Randomized clinical trials failed to show a survival benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus concurrent chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC), with preclinical data suggesting potential negative interactions. In contrast, pilot trials of the EGFR-targeted antibody, cetuximab, plus chemotherapy suggested enhanced antitumor activity. This randomized phase II trial was designed to select a cetuximab plus chemotherapy regimen for phase III evaluation. Patients and Methods: Treatment-naive patients with advanced-stage NSCLC were randomly assigned to receive paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6) every 3 weeks plus concurrent cetuximab (400 mg/m2 loading dose followed by 250 mg/m2 weekly) for four cycles followed by maintenance cetuximab or sequential paclitaxel- carboplatin for four cycles followed by cetuximab. Results: Of 242 patients enrolled, 224 were eligible and assessable for response (106 and 118 patients in the concurrent and sequential arms, respectively). With a median follow-up time of 32 months, the median overall survival was 10.9 months (95{\%} CI, 9.2 to 13.0 months) for patients receiving concurrent therapy and 10.7 months (95{\%} CI, 8.5 to 12.8 months) for patients receiving sequential therapy (P = .57); 1-year survival rates were 45{\%} (95{\%} CI, 36{\%} to 54{\%}) and 44{\%} (95{\%} CI, 35{\%} to 53{\%}), respectively. Response rates and progression-free survival times were similar in both arms, as was grade 3 rash, whereas sensory neuropathy was higher in the concurrent arm (15{\%} v5{\%}in the sequential arm; P = .036). Conclusion: Although both regimens met the efficacy criterion for continued evaluation, the concurrent regimen of paclitaxel/carboplatin plus cetuximab was chosen.",
author = "Herbst, {Roy S.} and Karen Kelly and Kari Chansky and Philip Mack and Franklin, {Wilbur A.} and Hirsch, {Fred R.} and Atkins, {James N.} and Dakhil, {Shaker R.} and Albain, {Kathy S.} and Kim, {Edward S.} and Mary Redman and Crowley, {John J.} and Gandara, {David R}",
year = "2010",
month = "11",
day = "1",
doi = "10.1200/JCO.2009.27.9356",
language = "English (US)",
volume = "28",
pages = "4747--4754",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "31",

}

TY - JOUR

T1 - Phase II selection design trial of concurrent chemotherapy and cetuximab versus chemotherapy followed by cetuximab in advanced-stage non-small-cell lung cancer

T2 - Southwest Oncology Group study S0342

AU - Herbst, Roy S.

AU - Kelly, Karen

AU - Chansky, Kari

AU - Mack, Philip

AU - Franklin, Wilbur A.

AU - Hirsch, Fred R.

AU - Atkins, James N.

AU - Dakhil, Shaker R.

AU - Albain, Kathy S.

AU - Kim, Edward S.

AU - Redman, Mary

AU - Crowley, John J.

AU - Gandara, David R

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Purpose: Randomized clinical trials failed to show a survival benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus concurrent chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC), with preclinical data suggesting potential negative interactions. In contrast, pilot trials of the EGFR-targeted antibody, cetuximab, plus chemotherapy suggested enhanced antitumor activity. This randomized phase II trial was designed to select a cetuximab plus chemotherapy regimen for phase III evaluation. Patients and Methods: Treatment-naive patients with advanced-stage NSCLC were randomly assigned to receive paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6) every 3 weeks plus concurrent cetuximab (400 mg/m2 loading dose followed by 250 mg/m2 weekly) for four cycles followed by maintenance cetuximab or sequential paclitaxel- carboplatin for four cycles followed by cetuximab. Results: Of 242 patients enrolled, 224 were eligible and assessable for response (106 and 118 patients in the concurrent and sequential arms, respectively). With a median follow-up time of 32 months, the median overall survival was 10.9 months (95% CI, 9.2 to 13.0 months) for patients receiving concurrent therapy and 10.7 months (95% CI, 8.5 to 12.8 months) for patients receiving sequential therapy (P = .57); 1-year survival rates were 45% (95% CI, 36% to 54%) and 44% (95% CI, 35% to 53%), respectively. Response rates and progression-free survival times were similar in both arms, as was grade 3 rash, whereas sensory neuropathy was higher in the concurrent arm (15% v5%in the sequential arm; P = .036). Conclusion: Although both regimens met the efficacy criterion for continued evaluation, the concurrent regimen of paclitaxel/carboplatin plus cetuximab was chosen.

AB - Purpose: Randomized clinical trials failed to show a survival benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus concurrent chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC), with preclinical data suggesting potential negative interactions. In contrast, pilot trials of the EGFR-targeted antibody, cetuximab, plus chemotherapy suggested enhanced antitumor activity. This randomized phase II trial was designed to select a cetuximab plus chemotherapy regimen for phase III evaluation. Patients and Methods: Treatment-naive patients with advanced-stage NSCLC were randomly assigned to receive paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6) every 3 weeks plus concurrent cetuximab (400 mg/m2 loading dose followed by 250 mg/m2 weekly) for four cycles followed by maintenance cetuximab or sequential paclitaxel- carboplatin for four cycles followed by cetuximab. Results: Of 242 patients enrolled, 224 were eligible and assessable for response (106 and 118 patients in the concurrent and sequential arms, respectively). With a median follow-up time of 32 months, the median overall survival was 10.9 months (95% CI, 9.2 to 13.0 months) for patients receiving concurrent therapy and 10.7 months (95% CI, 8.5 to 12.8 months) for patients receiving sequential therapy (P = .57); 1-year survival rates were 45% (95% CI, 36% to 54%) and 44% (95% CI, 35% to 53%), respectively. Response rates and progression-free survival times were similar in both arms, as was grade 3 rash, whereas sensory neuropathy was higher in the concurrent arm (15% v5%in the sequential arm; P = .036). Conclusion: Although both regimens met the efficacy criterion for continued evaluation, the concurrent regimen of paclitaxel/carboplatin plus cetuximab was chosen.

UR - http://www.scopus.com/inward/record.url?scp=78149240941&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78149240941&partnerID=8YFLogxK

U2 - 10.1200/JCO.2009.27.9356

DO - 10.1200/JCO.2009.27.9356

M3 - Article

VL - 28

SP - 4747

EP - 4754

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 31

ER -