ALK Mutation Yields Poorer Survival in NSCLC Patients in Pre–ALK-Inhibitor Era

Patients with advanced non–small-cell lung cancer (NSCLC) who are ALK-positive had significantly worse survival outcomes compared with ALK-wild type patients, according to a study of patients treated in the pre–ALK-inhibitor era.

Human anaplastic lymphoma kinase in complex with crizotinib; source: A2-33, Wikimedia Commons

The EML4-ALK translocation is now considered a clear positive predictive marker of treatment with the ALK-inhibitor crizotinib (Xalkori), but the prognostic value in general of this mutation is not well known. Researchers at Seoul National University Hospital and elsewhere in South Korea reported results of a study including 262 total patients with advanced NSCLC, from which any patient who received crizotinib was excluded. The final analysis, including 23 ALK-positive patients, 46 EGFR mutation–positive patients, and 46 patients with wild type of both genes (WT/WT), was published in the July 15 issue of Cancer.

The median overall survival of the ALK-positive patients was 12.2 months; in the EGFR mutation–positive patients overall survival was 29.6 months (P = .001 vs ALK-positive). WT/WT patients had a median overall survival of 19.3 months (P = .127 vs ALK-positive). Progression-free survival was not significantly different between the groups, at 3.8 months, 4.9 months, and 3.7 months, respectively.

Progression-free survival following EGFR tyrosine kinase inhibitor (TKI) therapy, however, did yield differences; a total of 86 patients received an EGFR TKI, including 57 who received gefitinib (Iressa), 29 who received erlotinib (Tarceva), and 4 patients who received both. The median for ALK-positive patients was only 1.3 months, compared with 9.8 months in EGFR mutation–positive patients (P < .001 vs ALK-positive) and 2 months in WT/WT patients (P = .037 vs ALK-positive). Treatment response rates to cytotoxic chemotherapy did not differ between the three groups.

One of the study authors, Dong-Wan Kim, MD, PhD, of Seoul National University Hospital, said in an e-mail that the study’s key message is that “ALK-positive patients experienced poor survival outcomes compared with ALK-wild type patients in the pre–ALK-inhibitor era. Because [crizotinib] is available in the United States and Korea, this poor survival outcome could be improved.”

Study Details

Baseline characteristics of patients were generally well matched between the ALK-positive, EGFR mutation–positive, and WT/WT groups, with no significant differences with regard to age, gender, and smoking history. More patients in the EGFR mutation–positive group had adenocarcinomas than did those in the ALK-positive group (89.1% vs 69.6%, P = .043).

The most common first-line treatment received was a paclitaxel/carboplatin combination, followed by gemcitabine/vinorelbine. There were a variety of metastasis sites among all patients, with secondary lung sites and bone and CNS the most common.