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Randomized Controlled Trial
. 2012 Jun;7(6):963-72.
doi: 10.1097/JTO.0b013e31824fe9e6.

A pooled exploratory analysis of the effect of tumor size and KRAS mutations on survival benefit from adjuvant platinum-based chemotherapy in node-negative non-small cell lung cancer

Sinead Cuffe  1 , Abderrahmane Bourredjem, Stephen Graziano, Jean-Pierre Pignon, Caroline Domerg, Monia Ezzalfani, Lesley Seymour, Elizabeth Strevel, Ronald Burkes, Marzia Capelletti, Pasi A Jänne, Ming-Sound Tsao, Frances A Shepherd
Affiliations
Randomized Controlled Trial

A pooled exploratory analysis of the effect of tumor size and KRAS mutations on survival benefit from adjuvant platinum-based chemotherapy in node-negative non-small cell lung cancer

Sinead Cuffe et al. J Thorac Oncol. 2012 Jun.

Abstract

Introduction: The staging of node-negative non-small-cell lung cancer is modified in the 7th edition TNM classification. Here, we pool data from the National Cancer Institute of Canada Clinical Trials Group JBR.10 trial and the Cancer and Leukemia Group B-9633 trial to explore the prognostic and predictive effects of the new T-size descriptors and KRAS mutation status.

Methods: Node-negative patients were reclassified as T2a (>3-≤5 cm), T2b (>5-≤7 cm), T3 (>7 cm) or T ≤ 3 cm (≤3 cm, but other T2 characteristics).

Results: Of 538 eligible patients, 288 (53.5%) were T2a, 111 (21%) T2b, 62 (11.5%) T3, whereas 77 (14%) T≤3 cm were excluded to avoid confounding. KRAS mutations were detected in 104 of 390 patients (27%). T-size was prognostic for disease-free survival (p = 0.03), but borderline for overall survival (OS; p = 0.10), on multivariable analysis. Significant interaction between the prognostic value of KRAS and tumor size was observed for OS (p = 0.01), but not disease-free survival (p = 0.10). There was a nonsignificant trend (p = 0.24) for increased chemotherapy effect on OS with advancing T-size (hazard ratio [HR] T2a 0.90, [0.63-1.30]; T2b 0.69, [0.38-1.24]; and T3 0.57, [0.28-1.17]). The HR for chemotherapy effect on OS in T2a patients with KRAS wild-type tumors was 0.81 (p = 0.36), whereas a trend for detrimental effect was observed in those with mutant tumors (HR 2.11; p = 0.09; interaction p = 0.05). Similar trends were observed in T2b to T3 patients with wild-type (HR 0.86; p = 0.62), and KRAS mutant tumors (HR 1.16; p = 0.74; interaction p = 0.58).

Conclusion: Chemotherapy effect seems to increase with tumor size. However, this small study could not identify subgroups of patients who did or did not derive significant benefit from adjuvant chemotherapy based on T-size or KRAS status.

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Figures

Figure 1
Figure 1
Study Population
Figure 2
Figure 2
Disease-free (a) and overall survival (b) by tumor size in the control arm of the T-size population
Figure 2
Figure 2
Disease-free (a) and overall survival (b) by tumor size in the control arm of the T-size population
Figure 3
Figure 3
Overall survival by tumor size among the 390 patients with both T-size and KRAS data available: (a) KRAS wild-type and (b) KRAS mutated tumors (HR for univariable analysis).
Figure 3
Figure 3
Overall survival by tumor size among the 390 patients with both T-size and KRAS data available: (a) KRAS wild-type and (b) KRAS mutated tumors (HR for univariable analysis).
Figure 4
Figure 4
Disease-free survival (a-c) and overall survival (d-f) (chemotherapy versus control) in the T2a, Tb2 and T3 subgroups.
Figure 4
Figure 4
Disease-free survival (a-c) and overall survival (d-f) (chemotherapy versus control) in the T2a, Tb2 and T3 subgroups.
Figure 4
Figure 4
Disease-free survival (a-c) and overall survival (d-f) (chemotherapy versus control) in the T2a, Tb2 and T3 subgroups.
Figure 4
Figure 4
Disease-free survival (a-c) and overall survival (d-f) (chemotherapy versus control) in the T2a, Tb2 and T3 subgroups.
Figure 4
Figure 4
Disease-free survival (a-c) and overall survival (d-f) (chemotherapy versus control) in the T2a, Tb2 and T3 subgroups.
Figure 4
Figure 4
Disease-free survival (a-c) and overall survival (d-f) (chemotherapy versus control) in the T2a, Tb2 and T3 subgroups.
Figure 5
Figure 5
Overall survival curves (chemotherapy versus control) for the T2a and T2b-T3 subgroups among patients with KRAS wild type tumors (a,b) and patients with KRAS mutant tumors (c,d).
Figure 5
Figure 5
Overall survival curves (chemotherapy versus control) for the T2a and T2b-T3 subgroups among patients with KRAS wild type tumors (a,b) and patients with KRAS mutant tumors (c,d).
Figure 5
Figure 5
Overall survival curves (chemotherapy versus control) for the T2a and T2b-T3 subgroups among patients with KRAS wild type tumors (a,b) and patients with KRAS mutant tumors (c,d).
Figure 5
Figure 5
Overall survival curves (chemotherapy versus control) for the T2a and T2b-T3 subgroups among patients with KRAS wild type tumors (a,b) and patients with KRAS mutant tumors (c,d).
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