Mode of action afatinib* slide kit

Boehringer Ingelheim

The development of resistance to the first-generation EGFR tyrosine kinase inhibitors (TKI) has been demonstrated in NSCLC.1 One specific mechanism of resistance is the presence of a point mutation in the ATP-binding pocket referred to as the T790M mutation. This mutation, which may be either innate or acquired, renders these tumor cells insensitive to first-generation EGFR TKIs.2,3

BIBW 2992 (compound code of Afatinib) is being investigated as a novel, potent, small-molecule inhibitor of 2 members of the EGFR family: EGFR and HER2. In vitro, this agent irreversibly binds to and inhibits EGFR- and HER2-containing homodimers and heterodimers, thus preventing downstream signal transduction.4

References

1. Sequist LV. Oncologist. 2007;12(3):325-330.

2. Herbst RS, Heymach JV, Lippman SM. N Engl J Med. 2008;359(13):1367-1380.

3. Sharma SV, Bell DW, Settleman J, Haber DA. Nat Rev Cancer. 2007;7(3):169-181.

4. Li D, Ambrogio L, Shimamura L, et al. Oncogene. 2008;27(34):4702-4711.

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Source for healthcare professionals: www.inoncology.com
* Nintedanib (BIBF 1120), afatinib (BIBW 2992) and volasertib (BI 6727) are investigational compounds. Their safety and efficacy have not yet been fully established.

† Not an official event of the 2012 ASCO Annual Meeting. Not sponsored or endorsed by ASCO or the Conquer Cancer Foundation.

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