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
276P - Sarcopenia to predict overall survival in head and neck cancer patients receiving chemotherapy: A systematic review and meta-analysis
Presenter: Felix Kwenandar
Session: e-Poster Display Session
277P - Tegafur/uracil, platinum and cetuximab (UPEx) as first line treatment in frail patients with recurrent or metastatic head and neck squamous cell carcinoma
Presenter: Meng-che Hsieh
Session: e-Poster Display Session
278P - Serial assessment of parotid volume changes during radical chemoradiation of locally advanced head and neck cancer: Its implications in practice of adaptive radiotherapy
Presenter: Aathira T S
Session: e-Poster Display Session
279P - Clinico pathological characteristics and survival outcome in oral cavity cancer with masticator space involvement (T4b): A retrospective single institutional experience
Presenter: Abdulla Kunnummal Palathinkara
Session: e-Poster Display Session
280P - Safety and efficacy of concurrent chemoradiotherapy for head and neck cancers in younger versus older patients: Post hoc analysis of a randomized control trial
Presenter: Vanita Noronha
Session: e-Poster Display Session
281P - Prevalence of premalignant lesions and oral cancer among tobacco-using tea plantation workers of Nilgiri Hills, Tamilnadu, India
Presenter: Delfin Lovelina Francis
Session: e-Poster Display Session
282P - Filipino head and neck cancer patients and their quality of life
Presenter: Frederic Ivan Ting
Session: e-Poster Display Session
283P - Descriptive epidemiology of head and neck cancer in Niger: First results from the National Cancer Registry
Presenter: Salamatou Mamoudou Garba
Session: e-Poster Display Session
284P - Outcomes of metronomic adjuvant chemotherapy with tegafur-uracil in locally advanced head and neck squamous cell carcinoma
Presenter: Tsung-jang Yeh
Session: e-Poster Display Session
285P - Comparison of induction chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy alone in locally advanced nasopharyngeal carcinoma: A meta-analysis
Presenter: Xu Guoqiang
Session: e-Poster Display Session