An Italian randomized phase II study (GOIRC 02-2006 study) recently reported in Journal of Clinical Oncology by Andrea Ardizzoni, MD, of Azienda Ospedaliero-Universitaria in Parma, Italy, and colleagues showed no progression-free survival benefit of adding carboplatin to pemetrexed (Alimta) in second-line treatment of advanced non–small cell lung cancer (NSCLC).
Study Design
In GOIRC 02-2006, 239 patients with advanced NSCLC who had disease progression during or after first-line platinum-based chemotherapy were randomly assigned to receive pemetrexed plus carboplatin (n = 119) or pemetrexed alone (n = 120). Pemetrexed was given at 500 mg/m2 and carboplatin at area under the curve of 5 on day 1 of a 21-day cycle.
Patients in both the pemetrexed-plus-carboplatin and pemetrexed-alone groups had a median age of 64 years, 76% and 72% were male, 63% and 58% had ECOG performance status of 0, 82% and 83% had stage IV disease, 72% and 71% had adenocarcinoma, 37.5% and 35% had objective response to first-line platinum-based chemotherapy, and 62.5% and 64% had a treatment-free interval of at least 3 months.
The primary endpoint was progression-free survival. A preplanned pooled analysis of the results of this study combined with those of a nearly identical Dutch phase II study (NVALT7) was performed to assess the effect of the addition of carboplatin to pemetrexed on overall survival.
Key Results
Both groups had a median of four treatment cycles, and the median follow up was 22.2 months. Median progression-free survival was 3.5 months in the carboplatin-plus-pemetrexed group vs 3.6 months in the pemetrexed group (hazard ratio [HR] = 1.05, P = .706). Response occurred in 12.6% vs 12.5% of patients (P = .980). Median overall survival was 9.2 vs 8.8 months (HR = 0.97, P = .834).
Grade 3 or 4 hematologic toxicities and the most clinically relevant nonhematologic adverse events were infrequent and of similar incidence in the carboplatin-plus-pemetrexed group and the pemetrexed-alone group, including neutropenia (11.6% vs 10.3%), leukopenia (8.0% vs 13.7%), thrombocytopenia (8.0% vs 6.0%), anemia (5.4% vs 8.6%), fatigue (5.4% vs 6.8%), febrile neutropenia (2.7% vs 3.4%), and diarrhea, vomiting, and oral mucositis (each 0.9% vs 1.7%).
Overall Survival
The NVALT7 study (N = 240) showed a significant prolongation of progression-free survival with the addition of carboplatin to pemetrexed.2 Differences between GOIRC 02-2006 and NVALT7 included a greater proportion of men, better performance status, lower response rate to first-line chemotherapy, shorter treatment-free intervals prior to study treatment, and a greater proportion of patients with adenocarcinoma in GOIRC02-2006. The pooled analysis of overall survival showed no significant difference between carboplatin plus pemetrexed and pemetrexed alone (median 8.7 vs 8.2 months, HR = 0.90, P = .316).
A subgroup analysis in the pooled population indicated that the addition of carboplatin to pemetrexed resulted in a significant prolongation of median progression-free survival (3.2 vs 2.0 months, adjusted HR = 0.42, P < .001 for interaction by histologic subtype) and median overall survival (8.7 vs 5.4 months, HR = 0.58, P = .039 for interaction) among patients with squamous tumors. No such difference was seen among patients with nonsquamous tumors. ■
Disclosure: Among the study investigators, Drs. Andrea Ardizzoni, Marcello Tiseo, Corrado Boni, Filippo de Marinis, Lucio Crinò, and Egbert F. Smit have received honoraria from Eli Lilly. All other authors reported no potential conflicts of interest.
References
1. Ardizzoni A, Tiseo M, Boni L, et al: Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non–small-cell lung cancer (NSCLC): Results of GOIRC 02-2006 randomized phase II study and pooled analysis with NVALT7 trial. J Clin Oncol 30:4501-4507, 2012.
2. Smit EF, Burgers SA, Biesma B, et al: Randomized phase II and pharmacogenetic study of pemetrexed compared with pemetrexed plus carboplatin in pretreated patients with advanced non–small-cell lung cancer. J Clin Oncol 27:2038-2045, 2009.
