Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

The American Society of Clinical Oncology (ASCO) held their annual symposium on Gastrointestinal cancers over the weekend in Fort Lauderdale, FL.  I was unable to attend the meeting, but it was interesting to follow it remotely via various people at the event. 

In 2008, van Cutsem first presented the interim phase III data from the front line trial of cetuximab
(Erbitux) with FOLFIRI in metastatic colorectal cancer (mCRC) in a plenary session at the ASCO annual meeting.  The data demonstrated that biomarker data suggested that the presence of wild type rather than mutant type KRAS predicted response to cetuximab in mCRC.

The updated CRYSTAL data was
probably the most anticipated abstract at this meeting.  Here's a snapshot from the abstract:

Picture 200The data above clearly shows a superior response rate, progression-free survival (PFS) and overall survival (OS) in favour of cetuximab in wild type KRAS.

What was also interesting is that BRAF, another mutation that has been shown to increase resistance to EGFR inhibitors, was not predictive of cetuximab activity, based on pooled data from the CRYSTAL and OPUS trials presented by Prof Kohne.

Overall, these data indicate that testing for KRAS mutational status is a valid way of deciding which patients should receive EGFR inhibitors such as cetuximab for the treatment of metastatic colorectal cancer.  Patients with mutant KRAS or BRAF mutations are less likely to do well on such therapy.

It will be interesting to see whether future trials with a RAS/RAF inhibitor such as sorafenib (Nexavar) with cetuximab are being considered in combination to overcome resistance.

{Updated: I should clarify that the wt KRAS effect is an EGFR class effect as you can see from similar data on panitumumab (Vectibix) in the second line setting in this abstract

The presenter, Peeters, noted that in patients with wild type KRAS:

  • PFS was 5.9 months for panitumumab plus FOLFIRI
    vs. 3.9 months for FOLFIRI alone (HR=0.73). 
  • Median OS was
    14.5 months for the study arm vs. 12.5 months for FOLFIRI alone
    (HR=0.85). 
  • Response rate for the panitumumab arm was
    35% compared with 10% for patients assigned to FOLFIRI alone. 

As with cetuximab, there was no difference in PFS, OS or
response rate in patients with mutant KRAS tumours.  The study met its primary endpoint, so it will be interesting to see if regulatory approval will be forthcoming in the second line setting for panitumumab.}

Acknowledgement:  Many thanks to Kerri Wachter who was at the meeting and provided information and tips that lead to this post.

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2 Responses to “Erbitux improves survival in patients with metastatic colorectal cancer and wild type KRAS tumours”

  1. craig

    Do single-agent mTORs have much efficacy against KRAS mutations?

  2. MaverickNY

    There is evidence in preclinical studies in lung and CRC cell lines that it might be a good idea to try an mTOR or PI3K inhibitor, however, I’ve yet to see anything concrete in human trials. It may yet come.
    There was this interesting paper recently in NSCLC for example, on MEK inhibition, as the pathways are all related downstream:
    http://www.nature.com/bjc/journal/v100/n2/abs/6604886a.html
    Which one is the best target, no one knows yet!

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