Abstract 89P
Background
RAS status can impact on efficacy of chemotherapy for patients with metastatic tumor. However, we reported that RAS mutated clone can emerge in patients with RAS wild tumor, which suggest that the genotype of the tissue obtained at the time of diagnosis might not accurately represent, who are treated with EGFR blockade. In this study, we evaluated whether RAS mutation in tissue and/or in circulating tumor DNA (ctDNA) impact on efficacy of regorafenib. This is the biomarker analysis of RECC study, a phase II multicenter clinical trial in Japan, that confirmed the safety and effectiveness of dose escalation therapy of regorafenib in metastatic colorectal cancer (mCRC).
Methods
We conducted dose-escalation study as a single-arm, prospective, non-randomized, multi-centered open label phase II trial in Japan (RECC study). We set a starting dose of 80 mg/day during the first seven days, then will be increased up to 120 or 160 mg/day weekly. Before first administration of regorafenib, we extracted ctDNA and examined RAS mutation in ctDNA using droplet digital PCR (ddPCR).
Results
Fifty-eight patients with mCRC were registered in this study, and blood samples were available in 45 patients. In all obtained samples, ctDNA were successfully extracted from plasma and the quality and quantity of ctDNA were sufficient for genetic analysis. RAS mutation was detected in tumor tissue of 29 patients (64%) and in ctDNA of 21 patients (47%). In ctDNA, RAS mutation was detected in 21 of the 29 patients (72%) with RAS mutated tumor, and 6 of 16 patients with RAS wild tumor. Five of the 6 patients with RAS wild tumor were treated with EGFR blockade in previous treatment. RAS status both in tumor tissue and ctDNA had no impact on progression free survival and overall survival.
Conclusions
It was reported that RAS mutation has negative impact on efficacy of FTD/TPI. However, RAS mutation showed no impact on the efficacy of regorafenib. EGFR blockade have a potential to emerge RAS mutated clone. Thus, RAS status should be reconfirmed at the last minute before starting late line chemotherapy using liquid biopsy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
349P - Proteinuria in patients treated with ramcirumab increases the risk of renal dysfunction
Presenter: Kenta Hayashino
Session: e-Poster Display Session
350P - Rheumatologic immune related adverse events (irAEs) secondary to immune checkpoint inhibitor (ICI) therapy: A Western Australia experience
Presenter: Azim Khan
Session: e-Poster Display Session
351P - Valvular heart diseases in patients treated for breast cancer
Presenter: Ekaterina Kushnareva
Session: e-Poster Display Session
352P - Reproductive system disorders following chemotherapy in patients with breast cancer in Yogyakarta, Indonesia
Presenter: Irfan Haris
Session: e-Poster Display Session
353P - Survey for geriatric assessment in practising oncologists in India
Presenter: Vikas Talreja
Session: e-Poster Display Session
354P - Knowledge, perception, and attitude of oncology-related healthcare providers on complementary and alternative medicine (CAM)
Presenter: Chih Kiang Tan
Session: e-Poster Display Session
355P - Impact of comorbidities and rurality on treatment commencement, completion and outcomes, and health related quality of life, for geriatric oncology patients: Preliminary findings from a regional Australian study
Presenter: Mathew George
Session: e-Poster Display Session
357P - Comparison between immunotherapy and chemotherapy as neoadjuvant setting in resectable non-small cell lung cancer: A systematic review and meta-analysis of prospective trials
Presenter: Chao Zhang
Session: e-Poster Display Session
358P - Adjuvant tyrosine kinase inhibitors in non-squamous non-small cell lung cancer with EGFR driver mutations: An updated meta-analysis of randomized trials
Presenter: Joanmarie Balolong-Garcia
Session: e-Poster Display Session
359P - The role of adjuvant targeted therapy for postoperative EGFR mutant non-small cell lung cancer: A network meta-analysis
Presenter: Guang Ling Jie
Session: e-Poster Display Session