The evidence supporting this treatment comes from a non-inferiority, phase lll, randomised study to compare the overall survival between treatment arms in 1,725 chemotherapy naive patients with stage lllB or lV NSCLC and an ECOG PS of 0 to 1.
Patients received either cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 every 3 weeks or cisplatin 75 mg/m2 and gemcitabine 1,250 mg/m2 on day 1 every 3 weeks for up to six cycles.
A total of 1,725 patients were enrolled between July 2004 and December 2005, the baseline characteristics were balanced between the two arms. All patients were analysed for efficacy, 1,669 patients were analysed for safety. As of March 2007, 1,270 of the 1,725 patients had died, 75% cisplatin/gemcitabine arm and 72.3% cisplatin/pemetrexed arm.r
Optimal chemotherapy doublet
The predictive influence of histological subtypes on outcomes has been shown in recent studies. In a combined analysis of individual patient data from three phase III trials in first line treatment of NSCLC, Treat et alr demonstrated a difference in overall survival between patients with non-squamous and squamous histology to different chemotherapy combinations. In patients with non-squamous histology, pemetrexed/cisplatin conferred superior median overall survival (11 months) compared with other regimens including gemcitabine/carboplatin (8.3 months). However, in patients with squamous histology, vinorelbine/cisplatin conferred the best median overall survival outcome and gemcitabine/cisplatin was superior to pemetrexed/ cisplatin.
Progression free survival was non-inferior (cisplatin/pemetrexed median PFS, 4.8 months; cisplatin/gemcitabine median PFS, 5.1 months; HR = 1.04)
Objective response rates were comparable, whereas the duration of response was longer for cisplatin/gemcitabine than cisplatin/pemetrexed (4.5 v 5.1 months) although both were not statistically significant.r
|Overall survival (squamous cell carcinoma)
|| 9.4 months
|Overall survival (adenocarcinoma)
|| 12.6 months
Overall survival (large cell carcinoma)
|Overall survival non-squamous (adenocarcinoma + large cell carcinoma)
|Overall survival (other histology's)
|Overall survival 12 months
|Overall survival 24 months
Overall survival and progression free survival for the entire populationr
© J Clin Oncol 2008
© Lung Cancer 2012
Key haematologic grade 3 or 4 drug related toxicities were significantly (P < 0.001) lower for cisplatin/pemetrexed than cisplatin/gemcitabine (neutropenia, 15% v 27%; anaemia 6% v 10%, and thrombocytopenia 4% v 13% respectively).
No significant differences in hospital admissions or hospital days observed between the two groups.
Deaths attributed to study drug toxicity were low and were similar between arms 9 patients (1.0%) for cisplatin/pemetrexed and 6 patients (0.7%) for cisplatin/gemcitabine.r
© J Clin Oncol 2008