Does KRAS mutational status predict chemoresistance in advanced non-small cell lung cancer (NSCLC)?
BACKGROUND
Clinical implications of KRAS mutational status in advanced non-small cell lung cancer (NSCLC) remain unclear. To clarify this point, we retrospectively explored whether KRAS mutations could impact tumor response, and disease control rate (DCR) to first-line platinum-based chemotherapy (CT) as well as progression-free survival (PFS) or overall survival (OS).


METHODS
Between June 2009 and June 2012, 340 patients with advanced (stage IIIB/IV) NSCLC were reviewed in a single institution (Institut Gustave Roussy). Two hundred and one patients had a biomolecular profile and received a platinum-based first-line CT. Patients with an unknown mutational status or with actionable alterations were excluded. We retained two groups: patients with KRAS mutated tumor (MUT) and patients with wild-type KRAS/EGFR (WT). Multivariate analyses with Cox model were used. Survival curves were calculated with Kaplan-Meier method.


RESULTS
One hundred and eight patients were included in the analysis: 39 in the MUT group and 69 in the WT group. Baseline radiological assessment demonstrated more brain (P=0.01) and liver (P=0.04) metastases in MUT patients. DCR was 76% for MUT vs. 91% for WT group (P=0.03), regardless of the type of platinum-based CT (use of pemetrexed or not). Although no statistically significant differences were found, shorter PFS (4.9 vs. 6.0 months; P=0.79) and OS (10.3 vs. 13.2 months; P=0.40) were observed for patients with KRAS mutated tumors in univariate analysis.


CONCLUSIONS
KRAS mutant tumors had a lower DCR after the first-line platinum-based CT, but this difference did not translate in PFS or OS. The presence of KRAS mutations may confer a more aggressive disease, with greater baseline incidence of hepatic and cerebral metastases.
Department of Medical Oncology, Gustave Roussy, Villejuif, France; Department of Medical Oncology, University Hospital, Udine, Italy. Electronic address: m.macerelli@virgilio.it.
M
M
Macerelli
Department of Radiology, Gustave Roussy, Villejuif, France.
C
C
Caramella
Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France.
L
L
Faivre
Department of Medical Oncology, Gustave Roussy, Villejuif, France.
B
B
Besse
Department of Medical Oncology, Gustave Roussy, Villejuif, France.
D
D
Planchard
Department of Medical Oncology, Gustave Roussy, Villejuif, France; Department of Second Medical Oncology, Oncologic Venetian Institute, Padua, Italy.
V
V
Polo
Department of Medical Oncology, Gustave Roussy, Villejuif, France.
M
M
Ngo Camus
Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France.
A
A
Celebic
Translational Research Laboratory, Gustave Roussy, Villejuif, France.
V
V
Koubi-Pick
Translational Research Laboratory, Gustave Roussy, Villejuif, France.
L
L
Lacroix
Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France.
J P
JP
Pignon
Department of Medical Oncology, Gustave Roussy, Villejuif, France.
J C
JC
Soria
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D063646:Carcinogenesis; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D016019:Survival Analysis; D047368:Tumor Burden / Q000187:drug effects; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
Advanced non-small cell lung cancer; Chemoresistance; KRAS; Platinum-based chemotherapy; Specific point mutations; Tumor aggressiveness