Three-arm randomised controlled phase 2 study comparing pemetrexed and erlotinib to either pemetrexed or erlotinib alone as second-line treatment for never-smokers with non-squamous non-small cell lung cancer
In: European journal of cancer (1990), Jg. 49 (2013), Heft 15, S. 3111-3121
academicJournal
- print, 30 ref
Zugriff:
Background: This randomised controlled phase 2 study compared pemetrexed and erlotinib in combination with either agent alone in terms of efficacy and safety as second-line treatment in a clinically selected population of never-smokers with non-squamous non-small cell lung cancer (NSCLC). Methods: Patients who had failed only one prior chemotherapy regimen and had Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤2 were randomised to either: pemetrexed 500 mg/m2 on day 1 plus erlotinib 150 mg daily on days 2-14; erlotinib 150 mg daily; or pemetrexed 500 mg/m2 on day 1 of a 21-day cycle until discontinuation criteria were met. The primary endpoint, progression-free survival (PFS), was analysed using a multivariate Cox model. Firstly, a global comparison across the three arms was performed. If the global null hypothesis was rejected at a two-sided 0.2 significance level, pairwise comparisons of pemetrexed-erlotinib versus erlotinib or pemetrexed were then conducted using the same model. Statistical significance was claimed only if both global and pairwise null hypotheses were rejected at a two-sided 0.05 significance level. Findings: A total of 240 patients (male, 35%; East Asian, 55%; ECOG PS 0-1, 93%) were included. A statistically significant difference in PFS was found across the three arms (global p = 0.003), with pemetrexed-erlotinib significantly better than either single agent: HR = 0.57, 95% confidence interval (CI): 0.40―0.81, p = 0.002 versus erlotinib; HR = 0.58, 95% CI: 0.39― 0.85, p = 0.005 versus pemetrexed. Median PFS (95% CI) was 7.4 (4.4, 12.9) months in pemetrexed-erlotinib, 3.8 (2.7, 6.3) months in erlotinib and 4.4 (3.0, 6.0) months in pemetrexed. Safety analyses showed a higher incidence of drug-related grade 3/4 toxicity in pemetrexed-erlotinib (60.0%) than in pemetrexed (28.9%) or erlotinib (12.0%); the majority being neutropenia, anaemia, rash and diarrhoea. Interpretation: Pemetrexed―erlotinib significantly improved PFS compared to either drug alone in this clinically selected population. The combination had more toxicity, but was clinically manageable.
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Three-arm randomised controlled phase 2 study comparing pemetrexed and erlotinib to either pemetrexed or erlotinib alone as second-line treatment for never-smokers with non-squamous non-small cell lung cancer
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Autor/in / Beteiligte Person: | DAE HO, LEE ; JUNG SHIN, LEE ; XIN, WANG ; ALTUG, Sedat ; ORLANDO, Mauro ; KIM, Sang-We ; RODRIGUES-PEREIRA, José ; BAOHUI, HAN ; SONG, Xiang-Qun ; JIE, WANG ; KIM, Hoon-Kyo ; TARINI PRASAD, SAHOO ; DIGUMARTI, Raghunadharao |
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Zeitschrift: | European journal of cancer (1990), Jg. 49 (2013), Heft 15, S. 3111-3121 |
Veröffentlichung: | Kidlington: Elsevier, 2013 |
Medientyp: | academicJournal |
Umfang: | print, 30 ref |
ISSN: | 0959-8049 (print) |
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