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S.M. Lim
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-064 - A Randomized Phase II Trial of ERCC1 and RRM1 Expression-Based Chemotherapy versus Docetaxel/Carboplatin in Advanced Non-Small Cell Lung Cancer (ID 976)
09:30 - 09:30 | Author(s): S.M. Lim
- Abstract
Background:
Platinum-based doublet chemotherapy is still mainstay in treatment of advanced non-small-cell lung cancer (NSCLC). There was no molecular determinant for guiding platinum-based chemotherapy. Excision repair cross-complementing group 1 gene (ERCC1) is important for platinum-induced DNA adduct repair and ribonucleotide reductase subunit 1 (RRM1) is crucial for nucleotide metabolism and has been known for the dominant molecular determinant of gemcitabine efficacy. We assessed whether selection of first-line chemotherapy based on ERCC1 and RRM1 mRNA expression levels would improve clinical outcomes in patients with advanced NSCLC.
Methods:
Eligible patients were randomly assigned 1:1 to experimental arm and control arm. The experimental arm consisted of gemcitabine/carboplatin (GC) if ERCC1 and RRM1 were 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 docetaxel/carboplatin (DC). All chemotherapy regimens were to be continued for maximum 4 cycles every 3 weeks or unacceptable toxicity. ERCC1 and RRM1 mRNA expression were measured by quantitative real-time PCR in formalin-fixed paraffin-embedded (FFPE) tissue. The trial was powered for an 80% improvement in overall response rate (ORR, P0=0.25, P1=0.45, α=0.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. The study was prematurely terminated after the futility analysis of 42 PFS events, which showed a low conditional probability (conditional power=0.14) of a statistically significant outcome.
Results:
A total of 56 patients (n=26 in experimental arm, n=30 in control arm) were evaluable for efficacy and toxicity. Patient characteristics were well balanced in both groups. Majority of patients had adenocarcinoma histology (64.3%) and ECOG performance status 0 to 1 (96.4%). EGFR mutation was documented in 8 patients (4 in experimental arm, 4 in control arm). Among 26 patients in the experimental arm, mRNA expression of ERCC1 and RRM1 ranged from 0.18 to 2.81 (median, 0.69) and 0.22 to 16.65 (median, 0.66), respectively. Based on mRNA expression levels, 19 (73.1%) patients were assigned to GC, 0 (0.0%) to GV, 4 (15.4%) to DC, and 3 (11.5%) to VD. The median number of chemotherapy cycles delivered was 3.7 in experimental arm and 3.5 in control arm. The ORRs were 26.9% in experimental arm and 40.0% in control arm, which were not statistically significant (P=0.58). With a median follow-up of 30.1 months, median PFS was 4.6 months in experimental arm and 5.1 months in control arm (hazard ratio [HR] 1.27; 95% CI 0.69-2.31; P=0.43). Median OS was 18.2 months in experimental arm and was 12.6 months in control arm (HR 0.71; 95% CI 0.32-1.53; P=0.38). The occurrence of grade 3 or higher neutropenia (69.2% vs. 93.4%, P=0.02) and febrile neutropenia (3.8% vs. 23.3%, P=0.04) was significantly more common in control arm. There was no treatment-related death.
Conclusion:
ERCC1 and RRM1 expression-based chemotherapy did not improve clinical outcomes in advanced NSCLC (NCT01648517).
