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I. Jung
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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): I. Jung
- 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).
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-077 - A Randomized, Phase II Study of Nimotuzumab Plus Gefitinib vs Gefitinib in Advanced Non-Small Cell Lung Cancer After Platinum- Based Chemotherapy (ID 1176)
09:30 - 09:30 | Author(s): I. Jung
- Abstract
Background:
Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody. We aim to evaluate the efficacy of dual inhibition of EGFR with nimotuzumab plus gefitinib in advanced non-small cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy.
Methods:
An open label, randomized, phase II trial was conducted in 6 centers; 160 patients were randomized (1:1) to either nimotuzumab (200mg, IV weekly) plus gefitinib (250mg p.o. daily) or gefitinib alone until disease progression or intolerable toxicities. The primary endpoint was progression free survival (PFS) rate at 3 months. Secondary endpoints included PFS, overall survival (OS), overall response rate (ORR) and safety.
Results:
A total of 155 patients (78 in nimotuzumab plus gefitinib, 77 in gefitinib) were evaluable for efficacy and toxicity. Patient characteristics were well balanced in both groups. Majority of patients had adenocarcinoma histology (65.2%) and ECOG performance status 0 to 1 (83.5%). Among 102 patients with EGFR mutation results available, activating EGFR mutation was documented in 27 patients (12/50 in nimotuzumab plus gefitinib, 15/52 in gefitinib). With a median follow-up of 12.1 months, PFS rate at 3 months was 37.2% in nimotuzumab plus gefitinib and 48.1% in gefitinib [HR 1.03; 95% CI, 0.71–1.40; P=0.98]. Median PFS and OS were 2.0 months and 14.0 months in nimotuzumab plus gefitinib and 2.8 months and 13.2 months in gefitinib [HR 1.03, 95% CI 0.71-1.41, P=0.98 for PFS; HR 0.86, 95% CI 0.57–1.30, P=0.47 for OS]. The ORRs were 14.1% in nimotuzumab plus gefitinib and 22.1% in gefitinib, which was not statistically significant (P=0.76). As expected, patients with EGFR mutation showed significantly longer survival than those with wild-type EGFR or unknown EGFR mutation status (10.3 vs. 1.2 vs. 2.7 months, P < 0.001 for PFS; 23.5 vs. 13.5 vs. 10.5 months, P= 0.001 for OS). Combined treatment of nimotuzumab plus gefitinib did not show superior PFS compared to gefitinib alone in patients with EGFR mutation (13.5 vs. 10.2 months in gefitinib alone, P=0.30) and patients with wild-type EGFR (0.9 vs. 2.0 months in gefitinib alone, P=0.90). The median PFS was not significantly different between two treatment arms according to histology (2.8 vs. 2.9 months in gefitinib alone for adenocarcinoma, P=0.64; 1.2 vs. 2.8 months in gefitinib alone for non-adenocarcinoma, P=0.35). Adverse events (AEs) in both treatment arms were mostly grade 1 to 2 and easily manageable. Importantly, combined EGFR inhibition with nimotuzumab and gefitinib did not increase EGFR inhibition-related AEs, such as acneiform rash (32.4 vs. 30.3% in gefitinib alone, P=0.38), diarrhea (30.7 vs. 35.7% in gefitinib alone, P=0.32), and stomatitis (11.5 vs. 13.4% in gefitinib alone, P=0.19). There was no treatment-related death.
Conclusion:
The dual inhibition of EGFR with nimotuzumab plus gefitinib did not show superiority over gefitinib alone for second-line treatment of advanced NSCLC (NCT01498562).
