Survival Benefit of Pemetrexed in Lung Adenocarcinoma Patients With Anaplastic Lymphoma Kinase Gene Rearrangements

Abstract

Background: There have been conflicting findings regarding the efficacy of pemetrexed for lung cancer with anaplastic lymphoma kinase (ALK) rearrangement. This study was conducted to explore the benefits of pemetrexed in this patient group.

Patients and methods: Among patients who had received pemetrexed therapy between January 2010 and March 2014 for advanced stage lung adenocarcinoma, cases were selected with a confirmed ALK rearrangement, epidermal growth factor receptor (EGFR) mutation, or Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation. Clinical outcomes resulting from the pemetrexed-based regimen were analyzed according to the genetic alteration.

Results: A total of 442 patients were enrolled, including 52 with ALK translocation, 188 with EGFR mutation, 34 with KRAS mutation, and 168 wild type patients. The mean age was 57 ± 11 years and women were predominant in the ALK-positive and EGFR mutant groups. Pemetrexed-platinum combination therapy was usually performed as first-line therapy, whereas pemetrexed monotherapy was usually used as second-line therapy and beyond. The response rate (RR) was greater in the ALK-positive group than in the other groups (26.9% vs. 12.8%, 8.8%, and 18.5%; P = .046). The median progression-free survival (PFS) of ALK-positive patients was longer than that of the others (7.8 months vs. 2.5, 2.3, and 2.9 months; P < .001). This benefit on survival was more evident when pemetrexed was used as a single agent (P < .001).

Conclusion: ALK-positive patients showed a greater RR and longer PFS with pemetrexed-based therapy than patients without ALK rearrangements, suggesting that pemetrexed should be preferentially considered for the treatment of ALK-positive lung adenocarcinoma when use of crizotinib is not feasible.

Keywords: Anaplastic lymphoma kinase; Lung cancer; Pemetrexed; Progression-free survival.