Pemetrexed (Alimta) appears to be an effective treatment in persons with non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive, with such patients demonstrating a significantly better response to the drug than those whose cancer did not have this genetic mutation.
In Seoul, Korea, a total of 95 people with advanced NSCLC were genotyped into three groups: 43 (45%) had epidermal growth factor receptor (EGFR) mutations; 15 (16%) showed ALK rearrangement; and 37 (39%) had wild type NSCLC. Every 21 days, the participants received 500 mg of the chemotherapy agent pemetrexed, a folate analog metabolic inhibitor.
Tumor response was evaluated every two cycles or sooner if the patient exhibited clinical signs of progression. Patients continued treatment until disease progression warranted termination, until unacceptable toxicity was found, or until the patient or the physician decided to discontinue therapy.
Overall response rate to pemetrexed was superior in the ALK-translocated patients (46.7%) compared with the EGFR mutant (4.7%) and wild type (16.2%) patients. Time to progression was longer in the ALK-positive group (9.2 months) than in the EGFR mutant (1.4 months) or wild type (2.9 months) groups. Disease control rate, including partial response plus stable disease, was 86.7% for ALK-rearranged patients, 25.6% for EGFR mutant patients, and 56.8% for wild type patients.
The investigators called the ALK–positive overall response and disease control rates “excellent,” and deemed ALK positivity independently predictive of pemetrexed efficacy in NSCLC patients. However, they cautioned that the larger size of the EGFR mutant group may have affected results, and stated that further studies are needed (J Thorac Oncol. 2011;6:1474-1480).