articles for the new year!
by Kimberly Ha and Elizabeth Krutoholow
Source Pharmawire
09:11 Eli Lilly and Amgen: KRAS testing in colorectal cancer sees swift clinical adoption ahead of likely FDA re-labeling of Erbitux and Vectibix
Story * FDA label revisions for Lilly's Erbitux and Amgen's Vectibix likely
* ODAC panel member said she believes current retrospective data is adequate to support a label change
* Change in practice guidelines for KRAS testing already at the community physician level, not just academic centers
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Eli Lilly and Amgen's cancer drugs will see rapid adoption of routine KRAS gene testing for patients with advanced colorectal cancer, ahead of a likely FDA decision to relabel the drugs for use in only a subset of patients, according to physicians and industry executives.
Approximately one-third of patients with advanced colorectal cancer have mutated KRAS status.
There has been a wealth of research which suggests that patients with advanced colorectal cancer who have a mutation of the KRAS gene do not confer any benefit with treatments that inhibit the epidermal growth factor receptors (EGFR), said Nancy Roach, founder of the Colorectal Cancer Coalition.
These drugs include Lilly's Erbitux and Amgen's Vectibix - both which target the EGFR receptor - and have significant toxicities. Erbitux causes a severe, acne-like skin rash in certain patients, which ironically, acts as a predictive biomarker that the patient is responsive to the drug.
Numerous physicians from a number of different hospital networks throughout the US told this news service that KRAS testing is not only being conducted at academic centers, but that community physicians are also adopting the new practice guidelines ahead of the FDA's formal rulemaking decision.
"We’re not waiting for the FDA when there is fairly strong evidence to support testing patients for KRAS mutations," said Dr Wells Messersmith, director of gastrointestinal medical oncology at University of Colorado in Denver.
He added that academic centers in particular are using KRAS mutation testing as a prerequisite before using these drugs.
“We’re already doing KRAS testing for our patients at the University of Kansas Cancer Center,” said Dr Stephen Williamson, director of the oncology division there.
Right now, reimbursement is not a problem, he added. "Diagnostics are cheap and these drugs are expensive," said Dr Justin Stebbing, an oncologist at Imperial College London.
The National Comprehensive Cancer Network updated its colorectal cancer guidelines last year to include KRAS testing. More recently, the American Society of Clinical Oncology (ASCO) also recommended that patients test their tumors for KRAS gene status before treatment with Erbitux or Vectibix.
Dr Jean Grem, a voting panel member at the recent FDA ODAC meeting that discussed the KRAS issue, said she believes there is enough data in front of the agency to support relabeling these drugs with KRAS testing. "I have a feeling [that the FDA] probably will relabel. We don’t know for certain, but it seems this is widely adapted," said Grem.
"The FDA label is - I don’t want to say irrelevant - but the change in practice has already happened for most academic centers, and is growing steadily in private practice," said Messersmith.
Dr Stephen Little, the CEO of DxS, a personalized medicine company that has a KRAS test available, noted that a label change seems inevitable, because the FDA will likely accept the current retrospective studies - if they’re conducted properly - without requiring further prospective data. "But I don’t know if we will get formal guidance [on that issue]," he added.
Grem agreed that the FDA will likely discuss the importance of prospective data, and more of those studies will probably be conducted. But she added that the consensus at the ODAC panel was that the current retrospective data was adequate to support a label change. Grem already started conducting KRAS testing on her patients as soon as the data came out at last spring. "I think at the FDA, they were using the meeting as a forum to discuss the issue of how good the data has to be."
Physicians in private practice are also conducting KRAS testing, said Grem, who also noted that since the KRAS data garnered a lot of publicity at last year's ASCO meeting - testing is already being widely conducted not just at academic centers, but on a broader community level.
However, physicians stressed that just because a patient has normal KRAS status, and no gene mutation, it is not a guarantee that they will see a benefit. “Just because you have the normal KRAS status doesn’t mean you will benefit from these agents either. But it’s a definite way of screening out patients who will not benefit from treatment,” said Williamson.
"You’d be sparing a patient toxicities when they have no chance of benefit," said Grem.
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