Comparing Adjuvant Chemotherapy Regimens in Non–Small-Cell Lung Cancer

Chicago—A randomized phase 2 trial found that cisplatin plus pemetrexed was a safe and effective adjuvant chemotherapy regimen for patients with early-stage non–small-cell lung cancer (NSCLC). Patients taking cisplatin plus pemetrexed experienced less toxicity and superior dose delivery compared with those taking cisplatin plus vinorelbine. Michael Kreuter, MD, the study’s lead author, presented the results in an oral abstract session at the ASCO meeting and said a longer follow-up was needed to determine the regimen’s long-term efficacy. Dr. Kreuter said recent studies showed adjuvant chemotherapy significantly improved survival in patients with early-stage NSCLC. The 5-year survival benefit was approximately 5.4%, according to Dr. Kreuter, although toxicity is a major issue in platinum-based chemotherapy regimens. This study included patients if they had stage IB, IIA, IIB, or T3N1 NSCLC, an Eastern Cooperative Oncology Group score of 0 or 1, and were amenable to cisplatin treatment. They were randomized in a 1:1 ratio to receive 4 cycles every 4 weeks of 25 mg/m2 vinorelbine on days 1, 8, 15, and 22 and 50 mg/m2 cisplatin on days 1 and 8; or 4 cycles every 3 weeks of 500 mg/m2 pemetrexed on day 1 and 75 mg/m2 cisplatin on day 1. The researchers conducted the study between October 2006 and December 2009 at 16 sites and found 132 patients who met the eligibility criteria. The arms were well balanced. The median age was 59 years, and 74% of patients were males. They were treated until February 2010, with the end point analysis occurring in December 2010. The primary end point was clinical feasibility, defined as no death due to cancer, toxicity, or comorbidity; no nonacceptance by patients leading to premature withdrawal; and no observations of dose-limiting toxicity. The feasibility rate in the cisplatin plus pemetrexed group was 95.5% compared with 75.4% in the cisplatin plus vinorelbine group (P=.001). Of the patients taking cisplatin plus pemetrexed, 1.5% died and 3.0% experienced dose-limiting toxicity. Of the patients taking cisplatin plus vinorelbine, 3.1% died, 6.2% withdrew consent, and 15.4% experienced dose-limiting toxicity. In the cisplatin plus pemetrexed group, 74.6% of patients received treatment per the protocol compared with 20.0% of patients who took cisplatin plus vinorelbine (P<.0001). The mean duration of therapy was 11.2 months in the cisplatin plus pemetrexed group and 9.9 months in the cisplatin plus vinorelbine group, while the median number of cycles was 3.64 in the cisplatin plus pemetrexed group and 2.74 in the cisplatin plus vinorelbine group. In addition, 10.5% of patients in the cisplatin plus pemetrexed group had a grade 3 or 4 hematologic toxicity compared with 73.5% of patients in the cisplatin plus vinorelbine group (P<.0001). The main difference was found in the number of patients with neutropenia (9 vs 69). There was no significant difference between the groups in the percentage of grade 3 or 4 nonhematologic toxicities (P=.7988). The authors defined the time to treatment failure (TTTF) as the time from surgery to withdrawal because of an adverse event; progression/relapse/death; failure to return to therapy; or refusal of treatment/withdrawal of consent. The median TTTF was not reached in the cisplatin plus pemetrexed group and was 3.6 months in the cisplatin plus vinorelbine group (P<.001). At a mean follow-up of approximately 4 months, 1 patient had died in the cisplatin plus pemetrexed group and 2 patients had died in the cisplatin plus vinorelbine group.