This cross-trial pooled analysis aimed to demonstrate improved efficacy of pemetrexed (pem) - platinum (plat) followed by pem continuation maintenance over gemcitabine (gem)-cisplatin (cis) without maintenance in advanced nonsquamous non-small-cell lung cancer (NSQ NSCLC) patients.
Analysis populations consisted of patients with similar baseline characteristics selected from 3 trials (JMDB, PARAMOUNT, and JMII) using a propensity score method. JMDB investigated first-line pem-cis (pem 500 mg/m2 + cis 75 mg/m2 every 21 days [q21d] for 6 cycles) and gem-cis (gem 1250 mg/m2 on days 1, 8 + cis 75 mg/m2 day 1 q21d for 6 cycles). PARAMOUNT compared pem maintenance vs placebo after patients with NSQ NSCLC completed 4 cycles of first-line pem-cis without progressive disease (PD). JMII examined pem-carboplatin (carb) (pem 500 mg/m2 + carb area under the curve 6 mg/mL*min q21d for 4 cycles) induction therapy followed by pem maintenance in NSQ NSCLC patients. Kaplan-Meier method and Cox regression were used to analyze overall survival (OS) and progression-free survival (PFS). Statistical inference was conducted on the overall population (OP); the analysis on the maintenance eligible population (MEP [completed 4 cycles without PD]) was descriptive.
OP was created with 530 patients in pem-plat and 534 patients in gem-cis arms. Of these, 287 in pem-plat and 285 in gem-cis were the MEP. In the OP, significant improvement were observed in pem-plat group than gem-cis, both in PFS (hazard ratio [HR] = 0.87, 95% confidence interval (CI): 0.77-0.99, p = .029; median PFS 5.16 m vs 5.49 m) and in OS (HR = 0.79, 95% CI: 0.69-0.91, p = .001; median OS 12.29 m vs 10.91 m). For the MEP, both median PFS (7.39 m vs 6.64 m) and median OS (18.37 m vs 13.63 m) were prolonged in pem-plat compared with gem-cis.
This cross-trial analysis supports pem-plat induction followed by pem continuation maintenance therapy as a preferred choice over gem-cis without maintenance as first-line chemotherapy for patients with advanced NSQ NSCLC.
Clinical trial identification
1. JMDB: NCT00087711 (Last verified: May 2009). 2. PARAMOUNT: NCT00789373 (Last verified: March 2016). 3. JMII: NCT01020786 (Last verified: June 2013)
Legal entity responsible for the study
Eli Lilly and company
Eli Lilly and company
Y-L. Wu: Ongoing unpaid consultant with Eli Lilly and MSD, and has received speaker fee from Eli Lilly, Roche, Boehringer Ingelheim, and AstraZeneca. B. Zhang, X. Wang: Currently employee of Eli Lilly and Company. M. Orlando, H. Chi: Employee and shareholders of Eli Lilly and Company.