Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer: The AFFIRM study

G. Folprecht, C. Pericay, M. P. Saunders, A. Thomas, R. Lopez Lopez, J. K. Roh, V. Chistyakov, T. Höhler, Jun Suk Kim, R. D. Hofheinz, S. P. Ackland, D. Swinson, M. Kopp, D. Udovitsa, M. Hall, T. Iveson, A. Vogel, J. R. Zalcberg

Research output: Contribution to journalArticle

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Abstract

Background: The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC. Patients and methods: Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis. Results: Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% [95% confidence interval (CI) 17.2- 34.4] for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2-30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89-9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62-9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74-1.36). The response rates were 49.1% (95% CI 39.7-58.6) and 45.9% (95% CI 36.4-55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%). Conclusion: No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity.

Original languageEnglish
Article numbermdw176
Pages (from-to)1273-1279
Number of pages7
JournalAnnals of Oncology
Volume27
Issue number7
DOIs
Publication statusPublished - 2016 Jul 1

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oxaliplatin
Leucovorin
Fluorouracil
Colorectal Neoplasms
Confidence Intervals
Disease-Free Survival
Therapeutics
Survival Rate
aflibercept

Keywords

  • Aflibercept
  • Angiogenesis
  • Colorectal cancer
  • mFOLFOX6
  • Oxaliplatin

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer : The AFFIRM study. / Folprecht, G.; Pericay, C.; Saunders, M. P.; Thomas, A.; Lopez Lopez, R.; Roh, J. K.; Chistyakov, V.; Höhler, T.; Kim, Jun Suk; Hofheinz, R. D.; Ackland, S. P.; Swinson, D.; Kopp, M.; Udovitsa, D.; Hall, M.; Iveson, T.; Vogel, A.; Zalcberg, J. R.

In: Annals of Oncology, Vol. 27, No. 7, mdw176, 01.07.2016, p. 1273-1279.

Research output: Contribution to journalArticle

Folprecht, G, Pericay, C, Saunders, MP, Thomas, A, Lopez Lopez, R, Roh, JK, Chistyakov, V, Höhler, T, Kim, JS, Hofheinz, RD, Ackland, SP, Swinson, D, Kopp, M, Udovitsa, D, Hall, M, Iveson, T, Vogel, A & Zalcberg, JR 2016, 'Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer: The AFFIRM study', Annals of Oncology, vol. 27, no. 7, mdw176, pp. 1273-1279. https://doi.org/10.1093/annonc/mdw176
Folprecht, G. ; Pericay, C. ; Saunders, M. P. ; Thomas, A. ; Lopez Lopez, R. ; Roh, J. K. ; Chistyakov, V. ; Höhler, T. ; Kim, Jun Suk ; Hofheinz, R. D. ; Ackland, S. P. ; Swinson, D. ; Kopp, M. ; Udovitsa, D. ; Hall, M. ; Iveson, T. ; Vogel, A. ; Zalcberg, J. R. / Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer : The AFFIRM study. In: Annals of Oncology. 2016 ; Vol. 27, No. 7. pp. 1273-1279.
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title = "Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer: The AFFIRM study",
abstract = "Background: The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC. Patients and methods: Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis. Results: Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8{\%} [95{\%} confidence interval (CI) 17.2- 34.4] for the aflibercept/mFOLFOX6 arm and 21.2{\%} (95{\%} CI 12.2-30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95{\%} CI 7.89-9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95{\%} CI 7.62-9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95{\%} CI 0.74-1.36). The response rates were 49.1{\%} (95{\%} CI 39.7-58.6) and 45.9{\%} (95{\%} CI 36.4-55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8{\%} versus 17.2{\%}) and diarrhea (13.4{\%} versus 5.2{\%}). Neutropenia grade 3/4 occurred in 36.1{\%} versus 29.3{\%}. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3{\%} versus 1.7{\%}), proteinuria (9.2{\%} versus 0{\%}), deep vein thrombosis (5.9{\%} versus 0.9{\%}) and pulmonary embolism (5.9{\%} versus 5.2{\%}). Conclusion: No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity.",
keywords = "Aflibercept, Angiogenesis, Colorectal cancer, mFOLFOX6, Oxaliplatin",
author = "G. Folprecht and C. Pericay and Saunders, {M. P.} and A. Thomas and {Lopez Lopez}, R. and Roh, {J. K.} and V. Chistyakov and T. H{\"o}hler and Kim, {Jun Suk} and Hofheinz, {R. D.} and Ackland, {S. P.} and D. Swinson and M. Kopp and D. Udovitsa and M. Hall and T. Iveson and A. Vogel and Zalcberg, {J. R.}",
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TY - JOUR

T1 - Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer

T2 - The AFFIRM study

AU - Folprecht, G.

AU - Pericay, C.

AU - Saunders, M. P.

AU - Thomas, A.

AU - Lopez Lopez, R.

AU - Roh, J. K.

AU - Chistyakov, V.

AU - Höhler, T.

AU - Kim, Jun Suk

AU - Hofheinz, R. D.

AU - Ackland, S. P.

AU - Swinson, D.

AU - Kopp, M.

AU - Udovitsa, D.

AU - Hall, M.

AU - Iveson, T.

AU - Vogel, A.

AU - Zalcberg, J. R.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Background: The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC. Patients and methods: Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis. Results: Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% [95% confidence interval (CI) 17.2- 34.4] for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2-30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89-9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62-9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74-1.36). The response rates were 49.1% (95% CI 39.7-58.6) and 45.9% (95% CI 36.4-55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%). Conclusion: No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity.

AB - Background: The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC. Patients and methods: Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis. Results: Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% [95% confidence interval (CI) 17.2- 34.4] for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2-30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89-9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62-9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74-1.36). The response rates were 49.1% (95% CI 39.7-58.6) and 45.9% (95% CI 36.4-55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%). Conclusion: No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity.

KW - Aflibercept

KW - Angiogenesis

KW - Colorectal cancer

KW - mFOLFOX6

KW - Oxaliplatin

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