arrow4 Comments
  1. Andy
    Jun 27 - 5:38 am

    Hi Sally, nice write-ups. I’ve a question for both afatinib and selumetinib: what do you think of their safety profiles, which are also important in determining how useful they’ll be in practice? Thanks!

  2. Lila Guterman
    Jun 27 - 1:29 pm

    For more on afantinib and related drugs, check out the cover story I wrote last year in C&EN on covalent drugs: http://cen.acs.org/articles/89/i36/Covalent-Drugs-Form-Long-Lived.html

  3. sally
    Jun 28 - 2:12 pm

    Hi Andy, glad you liked the summary.

    From what I can recall from the ASCO presentations this year, afatinib has a similar safety profile to EGFR inhibitors such as erlotinib, with the acneiform rash being a class/TKI effect. Other common events included stomatitis/mucositis and paronychia (skin infections around the nails).

    Selumetinib and the MEK inhibitors are not the easier partner for combination therapy – they also tend to cause diarrhea (70% of patients experienced it in the trial reported, although none were grade 3/4) as well as nausea and vomiting. Grade 3/4 adverse events included acneiform rash 6.8% (vs none in the docetaxel arm) and asthenia. Hem toxicities were also slightly increased with the combination over docetaxel alone.

    Overall from talking to trialists at ASCO, my sense is that the MEK inhibitors will be tougher from a combination standpoint than pan ErbB inhibitors, although neither will be a walk in park.

  4. Elaine
    Aug 26 - 3:56 am

    Sally, could you kindly expound on comment on erbitux ‘unlikely to see much action in lung ca until a biomarker for it is found’? ECOG trial aside, does this mean that for patients considering tarceva+erbitux or afatinib + erbitux for maintenance NSCLC, these combos may actually just be better (and much cheaper) considered alone?

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