Epidermal growth factor receptor mutation status in circulating free DNA in serum: from IPASS, a phase III study of gefitinib or carboplatin/paclitaxel in non-small cell lung cancer

Koichi Goto, Yukito Ichinose, Yuichiro Ohe, Nobuyuki Yamamoto, Shunichi Negoro, Kazuto Nishio, Yohji Itoh, Haiyi Jiang, Emma Duffield, Rose McCormack, Nagahiro Saijo, Tony Mok, Masahiro Fukuoka
Journal of Thoracic Oncology 2012, 7 (1): 115-21

INTRODUCTION: In IPASS (IRESSA Pan-Asia Study), clinically selected patients with pulmonary adenocarcinoma received first-line gefitinib or carboplatin/paclitaxel. This preplanned, exploratory analysis was conducted to increase understanding of the use of surrogate samples, such as serum, versus tumor biopsy samples for determining EGFR mutation status in the Japanese cohort (n = 233).

METHODS: EGFR mutations were assessed using tumor tissue-derived DNA (n = 91) and circulating free (cf) DNA from pretreatment serum samples (n = 194).

RESULTS: Fewer patients were EGFR mutation positive when assessed using pretreatment cfDNA (23.7%) versus tumor tissue-derived DNA (61.5%). cfDNA results identified no false positives but a high rate of false negatives (56.9%). There was a significant interaction between cfDNA EGFR mutation status and treatment for progression-free survival (PFS) (p = 0.045). PFS was significantly longer and objective response rate (ORR) higher with gefitinib than carboplatin/paclitaxel in the cfDNA EGFR mutation-positive subgroup (PFS: hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.14-0.60; p < 0.001; ORR: odds ratio [OR], 1.71; 95% CI, 0.48-6.09; 75.0% versus 63.6%; p = 0.40). There was a slight numerical advantage in PFS and ORR for gefitinib over carboplatin/paclitaxel in the cfDNA EGFR mutation-negative subgroup, likely due to the high rate of false negatives within this subgroup.

CONCLUSIONS: These results merit further investigation to determine whether alternative sources of tumor DNA, such as cfDNA in serum, could be used for determining EGFR mutation status in future; currently, where a sample is available, analysis of tumor material is recommended.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"