By Edward C. Li, PharmD, BCOP, Drugs & Biologics Editor
In recent years, molecular marker testing has become more important in the clinical decision-making process for patients with cancer. Evidence has shown that some molecular and pharmacogenomics markers are correlated with both efficacy and toxicity in certain patient populations. However, routine testing for some of these markers can be considered premature, based on the available evidence. As such, practice patterns for ordering these tests are expected to vary in some cases. The NCCN Clinical Practice Guidelines (NCCN Guidelines™) for Breast, Colon, and Non-Small Cell Lung Cancers discuss the clinical utility of specific biomarkers and offer recommendations for routine evaluation when the evidence supports it.
The NCCN Guidelines™ for Non-Small Cell Lung Cancer (NSCLC) discuss EGFR mutations and the significant association between specific mutations and response to treatment with Tyrosine Kinase Inhibitors. However, the guidelines do not explicitly state that routine testing for these mutations should be part of the initial work up. As such, data from an NCCN Trends™ Survey shows that clinicians vary in their approaches to ordering molecular marker tests in NSCLC. According to this survey, which was conducted at the 2010 NCCN Annual Conference, 27% of respondents who treat NSCLC patients (n = 216) test for EGFR mutations before any systemic treatment is considered, compared to 24% who test for EGFR mutations only when treatment with an EGFR inhibitor is being considered. A smaller sample (12%) test for EGFR mutations only when there are clinical signs suggesting an EGFR mutation may be present and when they are considering treating with an EGFR inhibitor. Meanwhile, 30% of respondents do not routinely test for EGFR mutations in NSCLC.
For this survey, 405 respondents participated, with 40% of the respondents identifying themselves as practicing physicians in a cancer specialty. An additional 24% were advanced practitioners or nurses in oncology, and 6% were pharmacists specializing in oncology. The survey included questions on practice patterns for molecular and pharmacogenomics markers.
In the management of colon cancer, the practice of testing for KRAS mutations also varied. For those who treat colon cancer (n = 222), 51% of respondents test for KRAS mutations before any systemic therapy is considered, while 37% test for KRAS mutations when an EGFR inhibitor is being considered. A small number of respondents (12%) do not routinely test for KRAS mutations in colon cancer. The NCCN Guidelines for Colon Cancer discuss KRAS mutations and how they predict a lack of response to anti-EGFR antibodies. The guidelines “strongly recommend genotyping of tumor tissue in all patients with metastatic colorectal cancer at the time of diagnosis of stage IV disease.”
HER2 is another example of a biomarker that should be routinely evaluated. The NCCN Guidelines for Breast Cancer recommend determining HER2 status as part of the initial work up for patients with stage I-IV breast cancer. While this survey identified that the practice of testing for EGFR and KRAS is variable, the practice of testing for HER2 status in breast cancer is expectedly consistent. For those who treat breast cancer (n = 217), 92% of respondents test for HER2 status before systemic therapy is considered.
Which of the following BEST describes your practice in testing for HER2 status in patients with breast cancer?
Additionally, the practice of testing UGT1A1 status in patients being treated with irinotecan has not been well established, as recognized by the NCCN Guidelines for Colon Cancer. Consistent with this concept, this survey identified that 63% of respondents do not routinely test for UGT1A1 status in patients being considered for irinotecan therapy. For those who utilize the UGT1A1 testing, most is done in situations where a patient has already received irinotecan and has experienced toxicity attributed to irinotecan (16% of respondents).
Which of the following BEST describes your practice in testing for the homozygous UGT1A1*28 allele in patients receiving irinotecan?