A randomised, open-label phase II trial of afatinib versus cetuximab in patients with metastatic colorectal cancer

Authors: Hickish, T. et al.

Journal: European Journal of Cancer

Volume: 50

Issue: 18

Pages: 3136-3144

eISSN: 1879-0852

ISSN: 0959-8049

DOI: 10.1016/j.ejca.2014.08.008

Abstract:

Purpose This randomised phase II trial aimed to compare efficacy of the irreversible ErbB family blocker, afatinib, with cetuximab in patients with KRAS wild-type metastatic colorectal adenocarcinoma (mCRC) with progression following oxaliplatin- and irinotecan-based regimens. Efficacy in patients with KRAS mutations was also evaluated. Patients and methods Patients with KRAS wild-type tumours were randomised 2:1 to afatinib (40 mg/day, increasing to 50 mg/day if minimal toxicity) or cetuximab weekly (400 mg/m2 loading dose, then 250 mg/m2/week) according to number of previous chemotherapy lines. All patients with KRAS-mutated tumours received afatinib. Primary end-points were objective response (OR) for the wild-type group and disease control for the KRAS-mutated group. Secondary end-points were progression-free survival (PFS) and overall survival (OS). Results Patients with KRAS wild-type tumours (n = 50) received afatinib (n = 36) or cetuximab (n = 14). Unconfirmed and confirmed ORs were 3% and 0% for afatinib versus 20% and 13% for cetuximab (odds ratio: 0.122 [P = 0.0735] and <0.001, respectively). Median PFS was 46.0 and 144.5 days for afatinib and cetuximab, respectively. Median OS was 355 days with afatinib but not reached for cetuximab. In the KRAS-mutated group (n = 41), five (12%) patients achieved confirmed disease control (stable disease; P = 0.6394 [comparison versus 10%]); no ORs were reported. Median PFS and OS were 41.0 and 173 days, respectively. Most frequent treatment-related adverse events were diarrhoea and rash across groups. Conclusions The efficacy of afatinib was inferior to cetuximab in patients with KRAS wild-type mCRC. In patients with KRAS-mutated tumours, disease control was modest with afatinib. Afatinib had a manageable safety profile.

Source: Scopus

A randomised, open-label phase II trial of afatinib versus cetuximab in patients with metastatic colorectal cancer.

Authors: Hickish, T. et al.

Journal: Eur J Cancer

Volume: 50

Issue: 18

Pages: 3136-3144

eISSN: 1879-0852

DOI: 10.1016/j.ejca.2014.08.008

Abstract:

PURPOSE: This randomised phase II trial aimed to compare efficacy of the irreversible ErbB family blocker, afatinib, with cetuximab in patients with KRAS wild-type metastatic colorectal adenocarcinoma (mCRC) with progression following oxaliplatin- and irinotecan-based regimens. Efficacy in patients with KRAS mutations was also evaluated. PATIENTS AND METHODS: Patients with KRAS wild-type tumours were randomised 2:1 to afatinib (40 mg/day, increasing to 50 mg/day if minimal toxicity) or cetuximab weekly (400 mg/m2 loading dose, then 250 mg/m2/week) according to number of previous chemotherapy lines. All patients with KRAS-mutated tumours received afatinib. Primary end-points were objective response (OR) for the wild-type group and disease control for the KRAS-mutated group. Secondary end-points were progression-free survival (PFS) and overall survival (OS). RESULTS: Patients with KRAS wild-type tumours (n=50) received afatinib (n=36) or cetuximab (n=14). Unconfirmed and confirmed ORs were 3% and 0% for afatinib versus 20% and 13% for cetuximab (odds ratio: 0.122 [P=0.0735] and <0.001, respectively). Median PFS was 46.0 and 144.5 days for afatinib and cetuximab, respectively. Median OS was 355 days with afatinib but not reached for cetuximab. In the KRAS-mutated group (n=41), five (12%) patients achieved confirmed disease control (stable disease; P=0.6394 [comparison versus 10%]); no ORs were reported. Median PFS and OS were 41.0 and 173days, respectively. Most frequent treatment-related adverse events were diarrhoea and rash across groups. CONCLUSIONS: The efficacy of afatinib was inferior to cetuximab in patients with KRAS wild-type mCRC. In patients with KRAS-mutated tumours, disease control was modest with afatinib. Afatinib had a manageable safety profile.

Source: PubMed

A randomised, open-label phase II trial of afatinib versus cetuximab in patients with metastatic colorectal cancer

Authors: Hickish, T. et al.

Journal: EUROPEAN JOURNAL OF CANCER

Volume: 50

Issue: 18

Pages: 3136-3144

eISSN: 1879-0852

ISSN: 0959-8049

DOI: 10.1016/j.ejca.2014.08.008

Source: Web of Science (Lite)

A randomised, open-label phase II trial of afatinib versus cetuximab in patients with metastatic colorectal cancer.

Authors: Hickish, T. et al.

Journal: European Journal of Cancer

Volume: 50

Pages: 3136-3144

Source: Manual

Preferred by: Tamas Hickish

A randomised, open-label phase II trial of afatinib versus cetuximab in patients with metastatic colorectal cancer.

Authors: Hickish, T. et al.

Journal: European journal of cancer (Oxford, England : 1990)

Volume: 50

Issue: 18

Pages: 3136-3144

eISSN: 1879-0852

ISSN: 0959-8049

DOI: 10.1016/j.ejca.2014.08.008

Abstract:

Purpose

This randomised phase II trial aimed to compare efficacy of the irreversible ErbB family blocker, afatinib, with cetuximab in patients with KRAS wild-type metastatic colorectal adenocarcinoma (mCRC) with progression following oxaliplatin- and irinotecan-based regimens. Efficacy in patients with KRAS mutations was also evaluated.

Patients and methods

Patients with KRAS wild-type tumours were randomised 2:1 to afatinib (40 mg/day, increasing to 50 mg/day if minimal toxicity) or cetuximab weekly (400 mg/m2 loading dose, then 250 mg/m2/week) according to number of previous chemotherapy lines. All patients with KRAS-mutated tumours received afatinib. Primary end-points were objective response (OR) for the wild-type group and disease control for the KRAS-mutated group. Secondary end-points were progression-free survival (PFS) and overall survival (OS).

Results

Patients with KRAS wild-type tumours (n=50) received afatinib (n=36) or cetuximab (n=14). Unconfirmed and confirmed ORs were 3% and 0% for afatinib versus 20% and 13% for cetuximab (odds ratio: 0.122 [P=0.0735] and <0.001, respectively). Median PFS was 46.0 and 144.5 days for afatinib and cetuximab, respectively. Median OS was 355 days with afatinib but not reached for cetuximab. In the KRAS-mutated group (n=41), five (12%) patients achieved confirmed disease control (stable disease; P=0.6394 [comparison versus 10%]); no ORs were reported. Median PFS and OS were 41.0 and 173days, respectively. Most frequent treatment-related adverse events were diarrhoea and rash across groups.

Conclusions

The efficacy of afatinib was inferior to cetuximab in patients with KRAS wild-type mCRC. In patients with KRAS-mutated tumours, disease control was modest with afatinib. Afatinib had a manageable safety profile.

Source: Europe PubMed Central