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J. Zhou
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MO12 - Prognostic and Predictive Biomarkers III (ID 96)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:B. Han, M. Edelman
- Coordinates: 10/29/2013, 10:30 - 12:00, Parkside Ballroom B, Level 1
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MO12.03 - Biomarker analysis of a randomized, controlled, multicenter clinical trial comparing pemetrexed/cisplatin and gmcitabine/cisplatin as first-line treatment for advanced nonsquamous non-small cell lung cancer (ID 3483)
10:40 - 10:45 | Author(s): J. Zhou
- Abstract
- Presentation
Background
The platinum-based doublet regimen was standard of care in advanced non-small cell lung cancer (NSCLC), but the biomarkers to predict the efficacy of first-line chemotherapy is still controversial.Methods
We collected 239 tumor samples (83.0%) from a a randomized, controlled, multicenter clinical trial, which enrolled 288 treatment naïve nonsquamous NSCLC patients who were randomly assigned (1:1) to experimental group to receive cisplatin plus pemetrexed (PC) or the control group to receive gemcitabine plus cisplatin (GC) every 3 weeks for up to 6 cycles. We evaluated the EGFR mutation by Amplification Refractory Mutation System(ARMS) method and EML4-ALK fusion by real-time PCR. Meanwhile, the mRNA expression of excision repair cross complementation 1 (ERCC-1), thymidylate synthase (TS), ribonucleotide reductase M1(RRM-1), and folatereceptor 1(FR-1) was tested by real-time PCR. All of the EGFR mutation, ALK fusion and mRNA expression were analyzed for the correlation with progression free survival, the primary endpoint in the tiral.Results
The EGFR mutation rate was 46.6%(110/236) in the overall population and the ALK fusion rate was 12.0%(29/233). The median PFS was similar between the EGFR mutated patients and wild-type patients(6.0m vs 5.7m,p=0.85), however, the patients of EGFR wild-type had better PFS in the PC group compared with GC group (5.7m vs 3.5m, p=0.03). There are no significant difference between groups in EGFR mutated patients(5.6m vs 6.1m, p=0.59). The patients with ALK fusion seem to have better PFS compared with fusion negative patients (7.7m vs 5.7m), but the difference is not significant(p=0.48). The mRNA expression level was available in 225 patients(94.1%) and we determined the median expression as the cutoff value. The TS expression is significantly correlated with ERCC-1(r=0.67,p<0.001) and negatively correlated with FR-1 expression(r=-0.21,p=0.002). EGFR mutation correlated with lower TS expression(p=0.034) and ALK fusion correlated with higher FR-1 expression(p=0.017). The differences of PFS between the high and low expression of ERCC-1, TS, RRM-1and FR-1 was not significant, in both PC group and GC group.Conclusion
The expression level of ERCC-1, TS, RRM-1and FR-1 could not effectively predict the progression free survival of NSCLC patients receiving platinum-based doublet regimen. The pemetrexed plus cisplatin regimen should be the priority choice for EGFR wild type patients compared with gemcitabine plus cisplatin regimen.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:
- Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P2.11-017 - Icotinib in advanced lung adenocarcinoma patients pretreated with pemetrexed (ID 1604)
09:30 - 09:30 | Author(s): J. Zhou
- Abstract
Background
In non-small cell lung cancer (NSCLC), the well-developed epidermal growth factor receptor (EGFR) is important therapeutic target. EGFR activating gene mutations have been proved strongly predictive of response to EGFR-tyrosine kinase inhibitors in NSCLC. However, both in daily clinical practice and clinical trials, patients with unknown EGFR gene status (UN-EGFR-GS) are very common. In this study, we assessed efficacy and tolerability of sequential treatment of first-line pemetrexed followed by icotinib in Chinese advanced lung adenocarcinoma with UN-EGFR-GS.Methods
We retrospectively analyzed 15 patients with advanced lung adenocarcinoma, who were treated first-line chemotherapy with pemetrexed and sequential using icotinib. The clinical characteristics, toxicity and survival status were collected through reviewing medical records, electronic preserved data, interviewing with patients or their family members. The overall survival (OS) was defined as the time of starting pemetrexed treatment to death or lost to follow up. The clinical course of included patients and treatment were prospectively monitored.Results
Totally, 15 patients with advanced lung adenocarcinoma were included, 9 females, 6 males. The median age is 57 years old (ranges: 40-73y). Of the 15 patients, 11 were non-smokers and 4 were smokers. All the patients at least received one cycle of pemetrexed chemotherapy, and then were administered with icotinib. Four cases were received pemetrexed combined with carboplatin, 8 combined with cisplatin, and 3 as single use. The mean cycles of pemetrexed given to patients were 3.8(1-6cycles). The response rate to pemetrexed was 20.0% (3/15), stable disease 33.3% (5/15), progressive disease 40% (6/15). The icotinib use of 4 patients was for the purpose of maintenance therapy, 11 for second line. The response rate to icotinib was 40% (6/15), stable disease 26.7% (4/15), progressive disease 33.3% (5/15). There was no grade 3-4 toxicities observed during icotinib treatment phase. The most common grade 1-2 toxicities were rashes (26.7%), diarrheas (30%), elevated aminotransferase (13.3%) and elevated BUN (6.7%). At the end of follow up, 8 patients were dead, 7 alive. The median OS was 22.6 months. Two patients were still on icotinib treatment.Conclusion
The sequence of first-line pemetrexed-based chemotherapy followed by icotinib treatment is a promising option for advanced lung adenocarcinoma with UN-EGFR-GS in China. The sequence yielded promising results with acceptable toxicity. The role of the sequential model for advanced NSCLC patients with adenocarcinoma histology should be further investigated in studies with larger sample sizes.
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P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:
- Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P3.11-015 - An open label, dose escalation, phase I trial to evaluate the tolerability and antitumor activity of icotinib in patients with advanced non-small-cell lung cancer (ID 1499)
09:30 - 09:30 | Author(s): J. Zhou
- Abstract
Background
A phase I, dose escalation study was conducted to evaluate the safety and antitumor activity of icotinib, an oral epidermal growth factor receptor inhibitor which was approved for treating advanced non-small-cell lung cancer (NSCLC) in China, and to explore its tolerable and effective dose range, and the maximum tolerated dose (MTD) in patients with advanced NSCLC.Methods
Patients were enrolled into sequential dose-escalating cohorts to receive icotinib orally three times daily (tid) from 225 mg/day to 1875 mg/day for at least 28 days. Escalation of icotinib was based on toxicities observed in the preceding dose cohort. Tumor response was assessed every 4 weeks.Results
103 patients were enrolled at 11 dose levels, including dose escalations and dose expansions. The most common drug-related adverse events were rash (51.5%, 53/103) and diarrhea (19.4%, 20/103), which were generally mild (grade 1/2) and revisable on symptomatic treatment. Two of six patients at 1875 mg/day experienced dose-limiting toxicity (grade 3 rash), and no further dose escalation occurred. Tumor responses were observed from 300 mg/day to 1875 mg/day. Out of 100 patients evaluable for tumor responses, the overall objective response rates and disease control rates were 27% and 76%, respectively, and the overall progression-free survival (PFS) was 5.0 months. Dose expansions were carried out in 300 mg/day, 375 mg/day and 450mg/day cohorts, and the median PFS for each cohort were 5.0 months, 5.6 months, and 4.0 months, respectively. Table 1: Safety profile of icotinib at various dose levels.
Table 2: Tumor response of icotinib at various dose levels.Dose (mg/tid) N Rash (N) Diarrhea (N) Overall adverse events (%) Overall adverse reaction (%) Grade I/II Grade III/IV Grade I/II Grade III/IV 75 7 5 - 1 - 85.7 (6/7) 85.7 (6/7) 100 27 6 1 7 - 70.4(19/27) 55.6(15/27) 125 24 13 1 4 - 75.0(18/24) 70.8(17/24) 150 13 6 - 1 - 69.2 (9/13) 69.2 (9/13) 200 3 1 - 1 - 100 (3/3) 100 (3/3) 250 8 4 - 1 - 75.0 (6/8) 62.5 (5/8) 300 3 2 - - - 100 (3/3) 100 (3/3) 350 3 1 - 1 - 100 (3/3) 100 (3/3) 400 3 3 - - - 100 (3/3) 100 (3/3) 500 6 5 1 1 - 100 (6/6) 100 (6/6) 625 6 3 2 2 - 100 (6/6) 100 (6/6) Total 103 49 5 20 - 79.6(82/103) 73.8(76/103) Dose (mg/tid) N CR/PR SD PD ORR (%) DCR (%) 75 6 0/0 6 0 -- -- 100 25 2/5 14 4 28 (7/25) 84 (21/25) 125 24 -/7 13 4 29.2 (7/24) 83.3 (20/24) 150 13 1/5 4 3 46.2 (6/13) 76.9 (10/13) 200 3 0/0 2 1 -- -- 250 8 0/1 4 3 12.5 (1/8) 62.5 (5/8) 300 3 0/0 2 1 -- -- 350 3 0/1 0 2 -- -- 400 3 0/2 0 1 -- -- 500 6 0/1 1 4 -- -- 625 6 0/1 1 4 -- -- Total 100 3/24 49 26 27(27/100) 76(76/100) Conclusion
Icotinib was well tolerated with manageable and revisable AEs at all dose levels. The MTD of icotinib was 1875 mg/day, and the tolerable and effective dose range was from 300 mg/day to 1875 mg/day. This study demonstrated that icotinib provided favorable safety profile and antitumor activity in advanced NSCLC patients.
