Alimta® Versus Its Combination With Carboplatin in Advanced Non-small-cell Lung Cancer in Patients Performance Status 2
Status:
Completed
Trial end date:
2012-12-01
Target enrollment:
Participant gender:
Summary
Optimal management of patients with advanced NSCLC and with PS 2 remains controversial and
underrepresented in clinical trials, typically accounting for 5 to 10% of enrolled patients.
Patient PS 2 proportion in population-based studies is considerably higher than that included
in clinical trials. Management of patients with PS of 2 in clinical practice is empirical and
inconsistent. Patients have median overall survival of 3 to 5 months in randomized trials,
and treatment options include best supportive care, single-agent and combination
chemotherapy. Retrospective studies have suggested that patients PS 2 may benefit from
first-line chemotherapy in terms of symptom improvement and overall survival. In many of
these studies, single-agent chemotherapy was compared with best supportive care alone. Data
on the role of cisplatin-based combinations for patients with PS 2 is more scant, with one
study questioning its benefit, and another interrupting accrual because of undue toxicity.
With regards to carboplatin, the Cancer and Leukemia Group B (CALGB) study 9730 compared
paclitaxel plus carboplatin versus paclitaxel alone in a subgroup of 107 patients with PS 2;
the median overall survival was significantly longer in group treated with combination
chemotherapy (4.7 versus 2.4 months). Combination chemotherapy with carboplatin and
paclitaxel also produced a statistically significantly higher incidence of severe
hematological and non-hematological toxicities. On the basis of aforementioned results, a
recent European panel stated that carboplatin-based or low-dose cisplatin-based doublets
might represent alternative options to single-agent chemoterapy in patients PS 2. Outside
clinical trials, single-agent chemotherapy with a 3rd generation agent remains valid option
for patients PS2. Results demonstrate that pemetrexed is an agent with established
single-agent activity in NSCLC, and suggest it is a potential candidate for combinations with
platinum and other agents currently utilized for patients with advanced NSCLC. Favorable
toxicity profile of pemetrexed suggests that this agent is an ideal candidate for single
agent testing and in combination among patients with PS 2. Substantial doubt remains in the
comparative benefit from monotherapy versus combination. Starting dose and schedule of
pemetrexed were set for this study based on its current labeling in the 2nd line treatment of
metastatic NSCLC and 1st line treatment of malignant pleural mesothelioma.