NO PROGNOSTIC ROLE OF p53/KRAS MUTATIONS IN LUNG CANCER

In a pooled analysis of four trials of platinum adjuvant therapy vs observation in resected early-stage non–small cell lung cancer (NSCLC), Shepherd et al found no prognostic effect of KRAS or EGFR with TP53 comutation but a potential negative predictive effect for adjuvant therapy with TP53 and KRAS comutation. These findings were reported in the Journal of Clinical Oncology.

Study Details

The study involved 3,633 patients in 3 trials from the LACE (Lung Adjuvant Cisplatin Evaluation) database comparing cisplatin-based therapy with observation and the CALBG 9633 trial comparing carboplatin-based therapy with observation in patients with resected disease. Mutation analyses for TP53, KRAS, and EGFR were blinded.

Prognostic and Predictive Effects

Of 3,533 patients with NSCLC, 1,181 (557 deaths) were used for TP53/KRAS analysis, and 404 (170 deaths) were used for TP53/EGFR analysis.

Among patients in the observational cohort, no prognostic effect for TP53/KRAS mutation status (mutant or wild-type) for overall survival was observed (P = .61). A predictive deleterious effect (P = .04) was observed for adjuvant chemotherapy in patients with TP53/KRAS comutations vs wild-type/wild-type (hazard ratio = 2.49, P = .03; P = .01 for interaction).

Among patients with adenocarcinoma, TP53/EGFR comutation was not prognostic in the observation cohort (P = .83) or predictive of outcome with chemotherapy (P = .86) for overall survival. Similar results were observed for TP53/KRAS analysis and TP53/EGFR analysis for disease-free survival.

The investigators concluded: “We could identify no prognostic effect of the KRAS or EGFR driver and TP53tumor suppressor comutation. Our observation of a potential negative predictive effect of TP53/KRAScomutation requires validation.”

The study was supported by F. Hoffmann-La Roche.

Frances A. Shepherd, MD, FRCPC, of Princess Margaret Cancer Centre, is the corresponding author of the Journal of Clinical Oncology article.