Phase III Study of Immediate Compared With Delayed Docetaxel After Front-Line Therapy With Gemcitabine Plus Carboplatin in Advanced Non-Small-Cell Lung Cancer

Eli Lilly, Indianapolis, Indiana, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 02/2009; 27(4):591-8. DOI: 10.1200/JCO.2008.17.1405
Source: PubMed

ABSTRACT Gemcitabine plus carboplatin (GC) is active as front-line treatment for advanced non-small-cell lung cancer (NSCLC). For patients without progression, timing of second-line chemotherapy for optimum clinical benefit remains uncertain. This phase III, randomized trial assessed the efficacy and safety of docetaxel administered either immediately after GC or at disease progression.
The chemotherapy-naïve patients enrolled had either stage IIIB NSCLC with pleural effusion or stage IV NSCLC. Gemcitabine (1,000 mg/m(2)) was administered on days 1 and 8 followed by carboplatin (area under the curve = 5) on day 1. After four 21-day cycles, patients who did not have progression were randomly assigned either to an immediate docetaxel group (docetaxel 75 mg/m(2) on day 1 every 21 days, with maximum of six cycles) or to a delayed docetaxel group. The primary end point was overall survival (OS) measured from random assignment. Additional analyses included tumor response, toxicity, progression-free survival (PFS), and quality of life (QOL).
Enrollment totaled 566 patients; 398 patients completed GC; 309 patients were randomly assigned equally to the two docetaxel treatment groups. Toxicity profiles were generally comparable for the docetaxel groups. Median PFS for immediate docetaxel (5.7 months) was significantly greater (P = .0001) than for delayed docetaxel (2.7 months). Median OS for immediate docetaxel (12.3 months) was greater than for delayed docetaxel (9.7 months), but the difference was not statistically significant (P = .0853). QOL results were not statistically different (P = .76) between docetaxel groups.
We observed a statistically significant improvement in PFS and a nonstatistically significant increase in OS when docetaxel was administered immediately after front-line GC, without increasing toxicity or decreasing QOL.

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Available from: Panos Fidias, Sep 25, 2014
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    • "The study showed a significant 3 months improvement in PFS and a non-statistically significant 2.5 months increase in OS in favor of the “immediate” docetaxel arm, with no increase in toxicity or decrease in QOL. Even though the patients in the delayed arm were carefully assessed and followed and that docetaxel was available to all of these patients, 37.2% of the patients in this arm did not receive docetaxel due to a rapid disease progression or a rapid PS decline (14). "
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    • "The rationale for this strategy is that continuous treatment could effectively delay disease progression and improve survival. Nowadays, various agents have been applied in maintenance regimens, such as bevacizumab,36,37 cetuximab,38,39 docetaxel,40 gemcitabine,41 and pemetrexed,42,43 for switching or continuous maintenance therapy. However, of interest, the most robust results were observed in clinical trials that evaluated EGFR TKIs (erlotinib or gefitinib) as switch maintenance agents (Table 3). "
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    • "In contrast, the SATURN trial found that erlotinib as a switch maintenance agent only yielded an OS benefit for patients with SD after induction (HR = 0.72 SD versus HR = 0.90 for patients with a tumor response),10 an outcome reflected in the maintenance indication for which erlotinib is approved for treatment in Europe. In a separate study by Fidias et al.,20 docetaxel was found to be effective as a switch maintenance agent only for the cohort of patients with a tumor response after induction (HR = 0.61 versus 1.02 for patients with SD).4 Results from the study by Pérol et al.11 led to the suggestion that induction response may affect survival results when using continuation maintenance. The post hoc analyses reported herein sought to further explore the initial PARAMOUNT finding. "
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