Randomized, Phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) Versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer

The PRIME study

Jean Yves Douillard, Salvatore Siena, James Cassidy, Josep Tabernero, Ronald Burkes, Mario Barugel, Yves Humblet, G. Bodoky, David Cunningham, Jacek Jassem, Fernando Rivera, Ilona Kocákova, Paul Ruff, Maria Błasińska-Morawiec, Martin Šmakal, Jean Luc Canon, Mark Rother, Kelly S. Oliner, Michael Wolf, Jennifer Gansert

Research output: Contribution to journalArticle

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Abstract

Purpose: Panitumumab, a fully human anti - epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS), is approved as monotherapy for patients with chemotherapyrefractory metastatic colorectal cancer (mCRC). The Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) was designed to evaluate the efficacy and safety of panitumumab plus infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as initial treatment for mCRC. Patients and Methods: In this multicenter, phase III trial, patients with no prior chemotherapy for mCRC, Eastern Cooperative Oncology Group performance status of 0 to 2, and available tissue for biomarker testing were randomly assigned 1:1 to receive panitumumab-FOLFOX4 versus FOLFOX4. The primary end point was PFS; overall survival (OS) was a secondary end point. Results were prospectively analyzed on an intent-to-treat basis by tumor KRAS status. Results: KRAS results were available for 93% of the 1,183 patients randomly assigned. In the wild-type (WT) KRAS stratum, panitumumab-FOLFOX4 significantly improved PFS compared with FOLFOX4 (median PFS, 9.6 v 8.0 months, respectively; hazard ratio [HR], 0.80; 95% CI, 0.66 to 0.97; P = .02). A nonsignificant increase in OS was also observed for panitumumab-FOLFOX4 versus FOLFOX4 (median OS, 23.9 v 19.7 months, respectively; HR, 0.83; 95% CI, 0.67 to 1.02; P = .072). In the mutant KRAS stratum, PFS was significantly reduced in the panitumumab-FOLFOX4 arm versus the FOLFOX4 arm (HR, 1.29; 95% CI, 1.04 to 1.62; P = .02), and median OS was 15.5 months versus 19.3 months, respectively (HR, 1.24; 95% CI, 0.98 to 1.57; P = .068). Adverse event rates were generally comparable across arms with the exception of toxicities known to be associated with anti-EGFR therapy. Conclusion: This study demonstrated that panitumumab-FOLFOX4 was well tolerated and significantly improved PFS in patients with WT KRAS tumors and underscores the importance of KRAS testing for patients with mCRC.

Original languageEnglish
Pages (from-to)4697-4705
Number of pages9
JournalJournal of Clinical Oncology
Volume28
Issue number31
DOIs
Publication statusPublished - Nov 1 2010

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oxaliplatin
Leucovorin
Fluorouracil
Colorectal Neoplasms
Disease-Free Survival
Survival
Therapeutics
Epidermal Growth Factor Receptor
panitumumab
Combination Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Randomized, Phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) Versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer : The PRIME study. / Douillard, Jean Yves; Siena, Salvatore; Cassidy, James; Tabernero, Josep; Burkes, Ronald; Barugel, Mario; Humblet, Yves; Bodoky, G.; Cunningham, David; Jassem, Jacek; Rivera, Fernando; Kocákova, Ilona; Ruff, Paul; Błasińska-Morawiec, Maria; Šmakal, Martin; Canon, Jean Luc; Rother, Mark; Oliner, Kelly S.; Wolf, Michael; Gansert, Jennifer.

In: Journal of Clinical Oncology, Vol. 28, No. 31, 01.11.2010, p. 4697-4705.

Research output: Contribution to journalArticle

Douillard, JY, Siena, S, Cassidy, J, Tabernero, J, Burkes, R, Barugel, M, Humblet, Y, Bodoky, G, Cunningham, D, Jassem, J, Rivera, F, Kocákova, I, Ruff, P, Błasińska-Morawiec, M, Šmakal, M, Canon, JL, Rother, M, Oliner, KS, Wolf, M & Gansert, J 2010, 'Randomized, Phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) Versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study', Journal of Clinical Oncology, vol. 28, no. 31, pp. 4697-4705. https://doi.org/10.1200/JCO.2009.27.4860
Douillard, Jean Yves ; Siena, Salvatore ; Cassidy, James ; Tabernero, Josep ; Burkes, Ronald ; Barugel, Mario ; Humblet, Yves ; Bodoky, G. ; Cunningham, David ; Jassem, Jacek ; Rivera, Fernando ; Kocákova, Ilona ; Ruff, Paul ; Błasińska-Morawiec, Maria ; Šmakal, Martin ; Canon, Jean Luc ; Rother, Mark ; Oliner, Kelly S. ; Wolf, Michael ; Gansert, Jennifer. / Randomized, Phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) Versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer : The PRIME study. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 31. pp. 4697-4705.
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title = "Randomized, Phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) Versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study",
abstract = "Purpose: Panitumumab, a fully human anti - epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS), is approved as monotherapy for patients with chemotherapyrefractory metastatic colorectal cancer (mCRC). The Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) was designed to evaluate the efficacy and safety of panitumumab plus infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as initial treatment for mCRC. Patients and Methods: In this multicenter, phase III trial, patients with no prior chemotherapy for mCRC, Eastern Cooperative Oncology Group performance status of 0 to 2, and available tissue for biomarker testing were randomly assigned 1:1 to receive panitumumab-FOLFOX4 versus FOLFOX4. The primary end point was PFS; overall survival (OS) was a secondary end point. Results were prospectively analyzed on an intent-to-treat basis by tumor KRAS status. Results: KRAS results were available for 93{\%} of the 1,183 patients randomly assigned. In the wild-type (WT) KRAS stratum, panitumumab-FOLFOX4 significantly improved PFS compared with FOLFOX4 (median PFS, 9.6 v 8.0 months, respectively; hazard ratio [HR], 0.80; 95{\%} CI, 0.66 to 0.97; P = .02). A nonsignificant increase in OS was also observed for panitumumab-FOLFOX4 versus FOLFOX4 (median OS, 23.9 v 19.7 months, respectively; HR, 0.83; 95{\%} CI, 0.67 to 1.02; P = .072). In the mutant KRAS stratum, PFS was significantly reduced in the panitumumab-FOLFOX4 arm versus the FOLFOX4 arm (HR, 1.29; 95{\%} CI, 1.04 to 1.62; P = .02), and median OS was 15.5 months versus 19.3 months, respectively (HR, 1.24; 95{\%} CI, 0.98 to 1.57; P = .068). Adverse event rates were generally comparable across arms with the exception of toxicities known to be associated with anti-EGFR therapy. Conclusion: This study demonstrated that panitumumab-FOLFOX4 was well tolerated and significantly improved PFS in patients with WT KRAS tumors and underscores the importance of KRAS testing for patients with mCRC.",
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TY - JOUR

T1 - Randomized, Phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) Versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer

T2 - The PRIME study

AU - Douillard, Jean Yves

AU - Siena, Salvatore

AU - Cassidy, James

AU - Tabernero, Josep

AU - Burkes, Ronald

AU - Barugel, Mario

AU - Humblet, Yves

AU - Bodoky, G.

AU - Cunningham, David

AU - Jassem, Jacek

AU - Rivera, Fernando

AU - Kocákova, Ilona

AU - Ruff, Paul

AU - Błasińska-Morawiec, Maria

AU - Šmakal, Martin

AU - Canon, Jean Luc

AU - Rother, Mark

AU - Oliner, Kelly S.

AU - Wolf, Michael

AU - Gansert, Jennifer

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Purpose: Panitumumab, a fully human anti - epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS), is approved as monotherapy for patients with chemotherapyrefractory metastatic colorectal cancer (mCRC). The Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) was designed to evaluate the efficacy and safety of panitumumab plus infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as initial treatment for mCRC. Patients and Methods: In this multicenter, phase III trial, patients with no prior chemotherapy for mCRC, Eastern Cooperative Oncology Group performance status of 0 to 2, and available tissue for biomarker testing were randomly assigned 1:1 to receive panitumumab-FOLFOX4 versus FOLFOX4. The primary end point was PFS; overall survival (OS) was a secondary end point. Results were prospectively analyzed on an intent-to-treat basis by tumor KRAS status. Results: KRAS results were available for 93% of the 1,183 patients randomly assigned. In the wild-type (WT) KRAS stratum, panitumumab-FOLFOX4 significantly improved PFS compared with FOLFOX4 (median PFS, 9.6 v 8.0 months, respectively; hazard ratio [HR], 0.80; 95% CI, 0.66 to 0.97; P = .02). A nonsignificant increase in OS was also observed for panitumumab-FOLFOX4 versus FOLFOX4 (median OS, 23.9 v 19.7 months, respectively; HR, 0.83; 95% CI, 0.67 to 1.02; P = .072). In the mutant KRAS stratum, PFS was significantly reduced in the panitumumab-FOLFOX4 arm versus the FOLFOX4 arm (HR, 1.29; 95% CI, 1.04 to 1.62; P = .02), and median OS was 15.5 months versus 19.3 months, respectively (HR, 1.24; 95% CI, 0.98 to 1.57; P = .068). Adverse event rates were generally comparable across arms with the exception of toxicities known to be associated with anti-EGFR therapy. Conclusion: This study demonstrated that panitumumab-FOLFOX4 was well tolerated and significantly improved PFS in patients with WT KRAS tumors and underscores the importance of KRAS testing for patients with mCRC.

AB - Purpose: Panitumumab, a fully human anti - epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS), is approved as monotherapy for patients with chemotherapyrefractory metastatic colorectal cancer (mCRC). The Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) was designed to evaluate the efficacy and safety of panitumumab plus infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as initial treatment for mCRC. Patients and Methods: In this multicenter, phase III trial, patients with no prior chemotherapy for mCRC, Eastern Cooperative Oncology Group performance status of 0 to 2, and available tissue for biomarker testing were randomly assigned 1:1 to receive panitumumab-FOLFOX4 versus FOLFOX4. The primary end point was PFS; overall survival (OS) was a secondary end point. Results were prospectively analyzed on an intent-to-treat basis by tumor KRAS status. Results: KRAS results were available for 93% of the 1,183 patients randomly assigned. In the wild-type (WT) KRAS stratum, panitumumab-FOLFOX4 significantly improved PFS compared with FOLFOX4 (median PFS, 9.6 v 8.0 months, respectively; hazard ratio [HR], 0.80; 95% CI, 0.66 to 0.97; P = .02). A nonsignificant increase in OS was also observed for panitumumab-FOLFOX4 versus FOLFOX4 (median OS, 23.9 v 19.7 months, respectively; HR, 0.83; 95% CI, 0.67 to 1.02; P = .072). In the mutant KRAS stratum, PFS was significantly reduced in the panitumumab-FOLFOX4 arm versus the FOLFOX4 arm (HR, 1.29; 95% CI, 1.04 to 1.62; P = .02), and median OS was 15.5 months versus 19.3 months, respectively (HR, 1.24; 95% CI, 0.98 to 1.57; P = .068). Adverse event rates were generally comparable across arms with the exception of toxicities known to be associated with anti-EGFR therapy. Conclusion: This study demonstrated that panitumumab-FOLFOX4 was well tolerated and significantly improved PFS in patients with WT KRAS tumors and underscores the importance of KRAS testing for patients with mCRC.

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