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MA16 - Novel Strategies in Targeted Therapy (ID 407)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
MA16.03 - Global RET Registry (GLORY): Activity of RET-Directed Targeted Therapies in RET-Rearranged Lung Cancers (ID 4325)
14:20 - 15:50 | Author(s): J. Shih
GLORY is a global registry of patients with RET-rearranged non-small cell lung cancer (NSCLC). In order to complement ongoing prospective studies, the registry’s goal is to provide data on the efficacy of RET-directed targeted therapies administered outside the context of a clinical trial. We previously reported results from our first interim analysis (Gautschi, ASCO 2016). Following additional accrual into the registry, updated results are presented here, with a focus on an expanded efficacy analysis of various RET inhibitors.
A global, multicenter network of thoracic oncologists identified patients with pathologically-confirmed NSCLC harboring a RET rearrangement. Molecular profiling was performed locally via RT-PCR, FISH, or next-generation sequencing. Anonymized data including clinical, pathologic, and molecular features were collected centrally and analyzed by an independent statistician. Response to RET tyrosine kinase inhibition (TKI) administered off-protocol was determined by RECIST1.1 (data cutoff date: April 15, 2016). In the subgroup of patients who received RET TKI therapy, the objectives were to determine overall response rate (ORR, primary objective), progression-free survival (PFS), and overall survival (OS).
165 patients with RET-rearranged NSCLC from 29 centers in Europe, Asia, and the USA were accrued. The median age was 61 years (range 28-89 years). The majority of patients were female (52%), never smokers (63%), with lung adenocarcinomas (98%) and advanced disease (91%). The most frequent metastasic sites were lymph nodes (82%), bone (51%) and lung (32%). KIF5B-RET was the most commonly identified fusion (70%). 53 patients received at least one RET-TKI outside of a clinical protocol, including cabozantinib (21), vandetanib (11), sunitinib (10), sorafenib (2), alectinib (2), lenvatinib (2), nintedanib (2), ponatinib (2) and regorafenib (1). In patients who were evaluable for response (n=50), the ORR was 37% for cabozantinib, 18% for vandetanib, and 22% for sunitinib. Median PFS was 3.6, 2.9, and 2.2 months and median OS was 4.9, 10.2, and 6.8 months for cabozantinib, vandetanib, and sunitinib, respectively. Responses were also observed with nintedanib and lenvatinib. Among patients who received more than one TKI (n=10), 3 partial responses were achieved after prior treatment with a different TKI.
RET inhibitors are active in individual patients with RET-rearranged NSCLC, however, novel therapeutic approaches are warranted with the hope of improving current clinical outcomes. GLORY remains the largest dataset of patients with RET-rearranged NSCLC, and continues to accrue patients.
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
P2.01-089 - Predictive Value of AEG-1 Expression on Tumor Response by Liquid Biopsy in NSCLC Patients Treated with Chemotherapy (ID 5679)
14:30 - 15:45 | Author(s): J. Shih
AEG‑1 is important in the aggressiveness of NSCLC and also contributes to induce chemoresistance in treatment of NSCLC. In this study, we will assess the predictive and prognostic values of AEG-1 expression on tumor response and survival according to mRNA concentration by liquid biopsy in NSCLC patients treated with chemotherapy.
Patients were diagnosed with a advanced NSCLC (stage IIIB and IV). Patients were enrolled to be treated by chemotherapy as first-line treatment or for metastatic or recurrent disease with Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. All patients underwent blood sampling before any cancer treatment and at first response evaluation. Response to chemotherapy was assessed using RECIST criteria. mRNA was extracted from plasma samples using the QIAamp Circulating Nucleic Acid Kit (Qiagen, Valencia, CA, USA) and quantification of mRNA was performed by real-time PCR (ABI 7900) with SYBR GREEN reagent expression assay for AEG-1.
A total of 12 patients (9 male and 3 female) with advanced NSCLC received platinum based doublets chemotherapy. Chemotherapy regimens included 8 cisplatin and 4 carboplatin with 5 pemetrexed, 4 paclitaxel, 2 gemcitabine and 1 vinorelbine. 7 of 12 (58.3%) were adenocarcinoma. The initial response rate of chemotherapy included 6 partial responses, 1 stable disease and 5 progressive disease. The expression level of AEG-1 in patients with disease progression after chemotherapy increased significantly compared with the expression level at pre-chemotherapy (AEG-1, relative quantification of mRNA, post-progression, range: 2.14 - 8.61, p = 0.035). In the group of patients with responsive chemotherapy, the mRNA expression level of AEG-1 was not increased compared to the baseline expression (Figure 1). Figure 1
This result suggests that mRNA concentration of AEG-1 from liquid biopsy could be a predictive biomarker of tumor response. Increased expression of AEG-1 contributed to the chemoresistance and caused lung cancer progression.