SPIRITT: A randomized, multicenter, phase II study of panitumumab with FOLFIRI and bevacizumab with FOLFIRI as second-line treatment in patients with unresectable wild type KRAS metastatic colorectal cancer

J. Randolph Hecht, Allen Cohn, Shaker Dakhil, Mansoor Saleh, Bilal Piperdi, Mika Cline-Burkhardt, Ying Tian, William Y. Go

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Abstract

Background Second-line treatment with chemotherapy and anti-epidermal growth factor receptor or anti-vascular endothelial growth factor antibodies improves outcomes in patients with wild type Kirsten rat sarcoma viral oncogene homolog (KRAS) metastatic colorectal cancer (mCRC). The choice of biological agent in second-line mCRC remains unclear. In this randomized, phase II estimation trial, we compared FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) in combination with panitumumab or bevacizumab in patients with disease progression during oxaliplatin-based chemotherapy and bevacizumab. Patients and Methods One hundred eighty-two patients were randomized to FOLFIRI with panitumumab or bevacizumab. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), and safety. Results PFS was similar between arms, with a hazard ratio (HR) of 1.01 (95% confidence interval [CI], 0.68-1.50; P =.97). Median PFS was 7.7 months (95% CI, 5.7-11.8) in the panitumumab arm and 9.2 months (95% CI, 7.8-10.6) in the bevacizumab arm. OS was also similar between arms, with an HR of 1.06 (95% CI, 0.75-1.49; P =.75). Median OS was 18.0 months (95% CI, 13.5-21.7) in the panitumumab arm and 21.4 months (95% CI, 16.5-24.6) in the bevacizumab arm. ORR was 32% (95% CI, 23%-43%) in the panitumumab arm and 19% (95% CI, 11%-29%) in the bevacizumab arm. Skin disorders, diarrhea, hypomagnesemia, hypokalemia, dehydration, and hypotension were more frequent in the panitumumab arm. Neutropenia was more frequent in the bevacizumab-containing arm. Conclusion Panitumumab or bevacizumab with FOLFIRI as second-line treatment had efficacy similar in patients whose disease progressed during oxaliplatin-based chemotherapy with bevacizumab, with expected toxicities. The development of more accurate biomarkers might help caregivers and patients to better choose between therapies for individual patients.

Original languageEnglish (US)
Pages (from-to)72-80
Number of pages9
JournalClinical Colorectal Cancer
Volume14
Issue number2
DOIs
StatePublished - Jun 1 2015

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Colorectal Neoplasms
Confidence Intervals
oxaliplatin
Disease-Free Survival
irinotecan
Therapeutics
Drug Therapy
Survival
panitumumab
Bevacizumab
Hypokalemia
Leucovorin
Biological Factors
Neutropenia
Oncogenes
Dehydration
Epidermal Growth Factor Receptor
Fluorouracil
Sarcoma
Hypotension

Keywords

  • EGFR
  • metastatic colorectal cancer
  • VEGF
  • WT

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

Cite this

SPIRITT : A randomized, multicenter, phase II study of panitumumab with FOLFIRI and bevacizumab with FOLFIRI as second-line treatment in patients with unresectable wild type KRAS metastatic colorectal cancer. / Hecht, J. Randolph; Cohn, Allen; Dakhil, Shaker; Saleh, Mansoor; Piperdi, Bilal; Cline-Burkhardt, Mika; Tian, Ying; Go, William Y.

In: Clinical Colorectal Cancer, Vol. 14, No. 2, 01.06.2015, p. 72-80.

Research output: Contribution to journalArticle

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title = "SPIRITT: A randomized, multicenter, phase II study of panitumumab with FOLFIRI and bevacizumab with FOLFIRI as second-line treatment in patients with unresectable wild type KRAS metastatic colorectal cancer",
abstract = "Background Second-line treatment with chemotherapy and anti-epidermal growth factor receptor or anti-vascular endothelial growth factor antibodies improves outcomes in patients with wild type Kirsten rat sarcoma viral oncogene homolog (KRAS) metastatic colorectal cancer (mCRC). The choice of biological agent in second-line mCRC remains unclear. In this randomized, phase II estimation trial, we compared FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) in combination with panitumumab or bevacizumab in patients with disease progression during oxaliplatin-based chemotherapy and bevacizumab. Patients and Methods One hundred eighty-two patients were randomized to FOLFIRI with panitumumab or bevacizumab. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), and safety. Results PFS was similar between arms, with a hazard ratio (HR) of 1.01 (95{\%} confidence interval [CI], 0.68-1.50; P =.97). Median PFS was 7.7 months (95{\%} CI, 5.7-11.8) in the panitumumab arm and 9.2 months (95{\%} CI, 7.8-10.6) in the bevacizumab arm. OS was also similar between arms, with an HR of 1.06 (95{\%} CI, 0.75-1.49; P =.75). Median OS was 18.0 months (95{\%} CI, 13.5-21.7) in the panitumumab arm and 21.4 months (95{\%} CI, 16.5-24.6) in the bevacizumab arm. ORR was 32{\%} (95{\%} CI, 23{\%}-43{\%}) in the panitumumab arm and 19{\%} (95{\%} CI, 11{\%}-29{\%}) in the bevacizumab arm. Skin disorders, diarrhea, hypomagnesemia, hypokalemia, dehydration, and hypotension were more frequent in the panitumumab arm. Neutropenia was more frequent in the bevacizumab-containing arm. Conclusion Panitumumab or bevacizumab with FOLFIRI as second-line treatment had efficacy similar in patients whose disease progressed during oxaliplatin-based chemotherapy with bevacizumab, with expected toxicities. The development of more accurate biomarkers might help caregivers and patients to better choose between therapies for individual patients.",
keywords = "EGFR, metastatic colorectal cancer, VEGF, WT",
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T2 - A randomized, multicenter, phase II study of panitumumab with FOLFIRI and bevacizumab with FOLFIRI as second-line treatment in patients with unresectable wild type KRAS metastatic colorectal cancer

AU - Hecht, J. Randolph

AU - Cohn, Allen

AU - Dakhil, Shaker

AU - Saleh, Mansoor

AU - Piperdi, Bilal

AU - Cline-Burkhardt, Mika

AU - Tian, Ying

AU - Go, William Y.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Background Second-line treatment with chemotherapy and anti-epidermal growth factor receptor or anti-vascular endothelial growth factor antibodies improves outcomes in patients with wild type Kirsten rat sarcoma viral oncogene homolog (KRAS) metastatic colorectal cancer (mCRC). The choice of biological agent in second-line mCRC remains unclear. In this randomized, phase II estimation trial, we compared FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) in combination with panitumumab or bevacizumab in patients with disease progression during oxaliplatin-based chemotherapy and bevacizumab. Patients and Methods One hundred eighty-two patients were randomized to FOLFIRI with panitumumab or bevacizumab. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), and safety. Results PFS was similar between arms, with a hazard ratio (HR) of 1.01 (95% confidence interval [CI], 0.68-1.50; P =.97). Median PFS was 7.7 months (95% CI, 5.7-11.8) in the panitumumab arm and 9.2 months (95% CI, 7.8-10.6) in the bevacizumab arm. OS was also similar between arms, with an HR of 1.06 (95% CI, 0.75-1.49; P =.75). Median OS was 18.0 months (95% CI, 13.5-21.7) in the panitumumab arm and 21.4 months (95% CI, 16.5-24.6) in the bevacizumab arm. ORR was 32% (95% CI, 23%-43%) in the panitumumab arm and 19% (95% CI, 11%-29%) in the bevacizumab arm. Skin disorders, diarrhea, hypomagnesemia, hypokalemia, dehydration, and hypotension were more frequent in the panitumumab arm. Neutropenia was more frequent in the bevacizumab-containing arm. Conclusion Panitumumab or bevacizumab with FOLFIRI as second-line treatment had efficacy similar in patients whose disease progressed during oxaliplatin-based chemotherapy with bevacizumab, with expected toxicities. The development of more accurate biomarkers might help caregivers and patients to better choose between therapies for individual patients.

AB - Background Second-line treatment with chemotherapy and anti-epidermal growth factor receptor or anti-vascular endothelial growth factor antibodies improves outcomes in patients with wild type Kirsten rat sarcoma viral oncogene homolog (KRAS) metastatic colorectal cancer (mCRC). The choice of biological agent in second-line mCRC remains unclear. In this randomized, phase II estimation trial, we compared FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) in combination with panitumumab or bevacizumab in patients with disease progression during oxaliplatin-based chemotherapy and bevacizumab. Patients and Methods One hundred eighty-two patients were randomized to FOLFIRI with panitumumab or bevacizumab. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), and safety. Results PFS was similar between arms, with a hazard ratio (HR) of 1.01 (95% confidence interval [CI], 0.68-1.50; P =.97). Median PFS was 7.7 months (95% CI, 5.7-11.8) in the panitumumab arm and 9.2 months (95% CI, 7.8-10.6) in the bevacizumab arm. OS was also similar between arms, with an HR of 1.06 (95% CI, 0.75-1.49; P =.75). Median OS was 18.0 months (95% CI, 13.5-21.7) in the panitumumab arm and 21.4 months (95% CI, 16.5-24.6) in the bevacizumab arm. ORR was 32% (95% CI, 23%-43%) in the panitumumab arm and 19% (95% CI, 11%-29%) in the bevacizumab arm. Skin disorders, diarrhea, hypomagnesemia, hypokalemia, dehydration, and hypotension were more frequent in the panitumumab arm. Neutropenia was more frequent in the bevacizumab-containing arm. Conclusion Panitumumab or bevacizumab with FOLFIRI as second-line treatment had efficacy similar in patients whose disease progressed during oxaliplatin-based chemotherapy with bevacizumab, with expected toxicities. The development of more accurate biomarkers might help caregivers and patients to better choose between therapies for individual patients.

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KW - VEGF

KW - WT

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