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Y. Moon
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-101 - Utility of Patient-Derived Cell Line Models Using Conditional Reprogramming for in Vitro Pharmacogenomics Platform (ID 963)
09:30 - 09:30 | Author(s): Y. Moon
- Abstract
Background:
To evaluate the potential of conditional reprogrammed cells (CRCs) established from biopsy or effusion samples of advanced non-small cell lung cancer (NSCLC) for in vitro pharmacologic screen and identification of drug resistance mechanisms.
Methods:
A total of 48 tumor specimens obtained from 46 patients with NSCLC were cultured with irradiated fibroblast feeder cells and Rho kinase inhibitor (Y-27632) to induce tumor cells to proliferate indefinitely. The cell lines established from patients harboring EGFR mutation or other druggable oncogenes were subjected to genetic analyses and pharmacologic screen. Corresponding tumor cells were injected into nude mice to test for tumorigenicity and efficacy of targeted agents in vivo.
Results:
Twenty one male patients and twenty five female patients were assessed for establishment of CRC. Adenocarcinoma was the most frequent histologic type (84.7%). There were 21 patients (46%) who harbored an active EGFR mutation. There were four patients with ALK fusion and five with ROS1 fusion. Twenty-six patients experienced disease progressed while on treatment with EGFR (20), ALK (2) or ROS1 (4) tyrosine kinase inhibitors. Tumor cells came from primary or distant metastases in 48% and 52%, respectively. Thirty one (65%) samples were obtained by tumor biopsy and 17 from malignant pleural effusion. Nine CRC model were successfully established (18.7%, 9/48). The successful growth was not dependent on the clinicopathologic characteristics. Both cells from pleural effusion (4 of 17) and biopsy (5 of 31) and adenocarcinoma (8 of 41) and squamous cell carcinoma (1 of 3) were successfully cultured. For biopsy samples, the success rate of cells obtained from primary lung lesion was 21.7% (5 of 23) and cells from metastatic site outside lung was 0% (0 of 8) (P = 0.3). For effusion samples, volume of effusion required for CRC was not significant factors for establishment (success vs. failure cases: mean volume 500 ml vs. 267 ml). The genetic characteristics of patients with non-squamous cell carcinoma did not affect the success rate of CRC (EGFR mutation, 4 of 21; ALK translocation, 0 of 4; ROS1 translocation, 2 of 5; wild or unknown, 2 of 15). Two xenograft models with CRC were successfully established and passaged to maintain tumor in vivo.
Conclusion:
The CRC models derived from NSCLC patients provide useful in vitro platforms of preclinical studies evaluating novel targeted therapies and uncovering the drug resistance mechanisms.
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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): Y. Moon
- 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).
