A phase II trial and a pooled analysis with another study found no benefit to adding carboplatin(Drug information on carboplatin) to pemetrexed(Drug information on pemetrexed) versus pemetrexed alone in previously treated patients with advanced non–small-cell lung cancer (NSCLC). There was a significant survival improvement, however, among a subgroup of patients with squamous tumors.
Study authors led by Andrea Ardizzoni, MD, of Azienda Ospedaliero-Universitaria in Parma, Italy, wrote in the Journal of Clinical Oncology that preclinical and phase I trials showed some antitumor activity when pemetrexed (Alimta) was combined with cisplatin and carboplatin. They conducted a randomized phase II study of 239 patients, and then pooled the results with a very similar study of 240 patients that commenced around the same time in the Netherlands.
In the main study, median progression-free survival was 3.5 months in the pemetrexed/carboplatin arm vs 3.6 months in the pemetrexed alone group (P = .706). Median overall survival was also similar, at 9.2 months in the experimental arm and 8.8 months in the standard therapy arm (P = .834). Serious hematologic and nonhematologic toxicities were similar between the two groups.
In a pooled analysis (total of 479 patients) with the other trial, known as NVALT7, the results were similar. The median overall survival for the pooled group of pemetrexed/carboplatin was 8.7 months, compared with 8.2 months in pemetrexed alone patients (HR, 0.90; 95% CI, 0.74–1.10; P = .316). The response rate was higher in the group who received the combination therapy, at 15% vs 9%. There was a nonsignificant increase in progression-free survival in the combination group as well, at 3.9 months vs 3 months.
A subgroup analysis showed that patients with squamous tumors did benefit from the addition of carboplatin to pemetrexed. These patients had a progression-free survival of 3.2 months compared with 2 months for pemetrexed alone (adjusted HR, 0.42; 95% CI, 0.27–0.65), and an overall survival of 8.7 months vs 5.4 months (adjusted HR, 0.58; 95% CI, 0.37–0.91). There was no difference between the treatment arms for nonsquamous tumors.
The authors noted that there was no correlation found between prior response to platinum-based first line chemotherapy and the addition of carboplatin to pemetrexed, contrary to hypotheses. “On the basis of this result, single-drug therapy with last-generation agents, such as pemetrexed or docetaxel(Drug information on docetaxel), should remain the standard of care in second-line chemotherapy treatment of NSCLC,” they wrote.
The US Food and Drug Administration (FDA) recently expanded the labeling for pemetrexed in light of recent research. Pemetrexed is currently approved as first-line therapy for locally advanced or metastatic non-squamous NSCLC in combination with cisplatin, and now as maintenance therapy for patients who have not progressed after first-line platinum-based chemotherapy. The new labeling includes results of a phase III randomized trial with 539 patients of pemetrexed maintenance therapy. Pemetrexed yielded significant improvements in both progression-free survival and overall survival compared with placebo for maintenance therapy.