Maintenance Therapy with Pemetrexed Improves Progression-Free Survival in Advanced Lung Cancer

Chicago—A randomized, double-blind, placebo-controlled phase 3 trial found that patients with advanced nonsquamous non–small-cell lung cancer (NSCLC) taking pemetrexed continuation maintenance therapy had a significantly improved progression-free survival compared with a placebo group. Luis Paz-Ares, MD, PhD, the study’s lead author, presented the results at the ASCO meeting in an oral abstract session. Dr. Paz-Ares said the trial indicated that pemetrexed maintenance therapy is effective following pemetrexed plus cisplatin induction therapy. He also said the study was fully powered for overall survival, and the authors plan on reporting the overall survival data when the minimum number of 390 events are reached. Dr. Paz-Ares said most patients with NSCLC have stage IIIB or IV disease when diagnosed and receive 4 to 6 courses of platinum-based combinations as first-line treatment. To prolong tumor response or stable disease, patients are treated with maintenance therapy. Previous trials showed pemetrexed was effective in treating advanced nonsquamous NSCLC as part of an induction regimen in combination with cisplatin and as a maintenance therapy for patients previously treated with a non-pemetrexed regimen. The study enrolled 939 patients in the induction phase, in which they received 4 cycles of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) on day 1 of a 21-day cycle. Of these patients, 539 did not experience disease progression during the induction phase and had an Eastern Cooperative Oncology Group performance status of 0 or 1. The 539 patients were randomized in a 2:1 ratio to receive maintenance pemetrexed (500 mg/m2 on day 1 of a 21-day cycle) plus best supportive care (n=359) or placebo plus best supportive care (n=180) until disease progression. Both arms also received folic acid and vitamin B12. The baseline characteristics were similar in the 2 groups. Approximately 58% of patients were male, approximately 95% were Caucasian, and the median age was approximately 62 years. Of the randomized patients, 333 in the pemetrexed group (92.8%) and 167 in the placebo group (92.8%) received treatment during the maintenance phase. In the pemetrexed group, the mean number of cycles per patient was 4.9 compared with 4.2 in the placebo group. At the time of the analysis, 302 progression-free survival events were recorded (184 in the pemetrexed group and 118 in the placebo group). Of the events, 95% were disease progression and 5% were deaths. Patients in the pemetrexed group had a median progression-free survival of 4.1 months compared with 2.8 months in the placebo group as assessed by the study’s investigators (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.49-0.79; P=.00006). The benefit favoring pemetrexed was consistent across all subgroups. An independent review of 88% of the patients found similar results, with a median progression-free survival of 3.9 months in the pemetrexed group and 2.6 months in the placebo group (HR, 0.64; 95% CI, 0.51-0.81; P=.0002). The response rate was 2.8% in the pemetrexed group compared with 0.6% in the placebo group (P=.176), while the disease control rate (percentage of patients with complete response, partial response, or stable disease) was 71.8% in the pemetrexed group compared with 59.6% in the placebo group (P=.009). The authors measured the health-related quality of life in both groups using the EQ-5D questionnaire at baseline, the first day of each cycle of induction or maintenance therapy, and at a 30-day post-discontinuation visit; there were no statistically significant differences between the groups. There was a statistically significant difference (P≤.05) in drug-related serious adverse events in the pemetrexed group (8.9%) compared with the placebo group (2.8%) as well as in the percentage of ≥1 grade 3 or 4 drug-related laboratory toxicities (9.2% for the pemetrexed group vs 0.6% in the placebo group; P≤.05). Dr. Paz-Ares said the main differences in grade 3 or 4 adverse events were found in fatigue, anemia, and neutropenia.