A randomized phase II trial of ERCC1 and RRM1 mRNA expression-based chemotherapy versus docetaxel/carboplatin in advanced non-small cell lung cancer.

Cancer Chemother Pharmacol 2016 Mar 25;77(3):539-48. Epub 2016 Jan 25.

Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Gu, Seoul, 120-752, Korea.

Objectives: To evaluate whether the selection of first-line chemotherapy based on ERCC1 and RRM1 mRNA expression levels would improve clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients.

Materials And Methods: Eligible patients were randomly assigned 1:1 to the experimental and control arms; the experimental arm received gemcitabine/carboplatin (GC) if ERCC1 and RRM1 expression was low, gemcitabine/vinorelbine (GV) if ERCC1 was high and RRM1 was low, docetaxel/carboplatin (DC) if ERCC1 was low and RRM1 was high, and docetaxel/vinorelbine (DV) if both were high. In the control arm, patients received DC.

Results: This study was prematurely terminated after the futility analysis of 43 progression-free survival (PFS) events. A total of 55 patients (n = 26 in the experimental arm, n = 29 in the control arm) were evaluable for efficacy and toxicity. Nineteen (73.1%) patients were assigned to receive GC, 0 (0.0%) to GV, 4 (15.4%) to DC, and 3 (11.5%) to DV in the experimental arm. The overall response rates were 42.3 and 48.3% in the experimental and control arms, respectively, which were not statistically different (P = 0.657). The median PFS was 5.2 months in the experimental arm and 5.4 months in the control arm (P = 0.286). The median overall survival was 17.4 months in the experimental arm and 12.6 months in the control arm (P = 0.638). The occurrence of grade 3 or higher neutropenia (69.2 vs. 93.1%, P = 0.035) and febrile neutropenia (3.8 vs. 24.1%, P = 0.054) was more common in the control arm.

Conclusion: ERCC1 and RRM1 mRNA expression-based chemotherapy did not improve clinical outcomes in advanced NSCLC (NCT01648517).

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http://dx.doi.org/10.1007/s00280-016-2968-zDOI Listing
March 2016
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