M Macerelli1, C Caramella2, L Faivre3, B Besse4, D Planchard4, V Polo5, M Ngo Camus4, A Celebic3, V Koubi-Pick6, L Lacroix6, J P Pignon3, J C Soria4. 1. Department of Medical Oncology, Gustave Roussy, Villejuif, France; Department of Medical Oncology, University Hospital, Udine, Italy. Electronic address: m.macerelli@virgilio.it. 2. Department of Radiology, Gustave Roussy, Villejuif, France. 3. Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France. 4. Department of Medical Oncology, Gustave Roussy, Villejuif, France. 5. Department of Medical Oncology, Gustave Roussy, Villejuif, France; Department of Second Medical Oncology, Oncologic Venetian Institute, Padua, Italy. 6. Translational Research Laboratory, Gustave Roussy, Villejuif, France.
Abstract
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.
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.
Authors: Lisa Maria Mustachio; Yun Lu; Laura J Tafe; Vincent Memoli; Jaime Rodriguez-Canales; Barbara Mino; Pamela Andrea Villalobos; Ignacio Wistuba; Hiroyuki Katayama; Samir M Hanash; Jason Roszik; Masanori Kawakami; Kwang-Jin Cho; John F Hancock; Fadzai Chinyengetere; Shanhu Hu; Xi Liu; Sarah J Freemantle; Ethan Dmitrovsky Journal: Mol Cancer Res Date: 2017-02-27 Impact factor: 5.852