Abstract 1802P
Background
Small cell lung cancer (SCLC) comprises approximately 15% of all lung cancers. It has a poor prognosis with a median overall survival (OS) of 7 months. Comprehensive genomic analyses of SCLC have reported MYC-amplification as a frequent oncogenic event in up to 30% of tumours and this correlates with an aggressive tumour phenotype and reduced OS. MYC status therefore has a prognostic role and is a potential future biomarker of response and/or treatment.
Methods
Recruitment for this study is ongoing. Blood from newly diagnosed or relapsed SCLC patients was analysed for circulating tumour DNA (ctDNA). Droplet digital PCR (ddPCR) detected the presence/absence of MYC C/L/N amplifications in ctDNA. A result was reported as amplified if ratio of MYC gene/reference gene was >2. Borderline amplified was reported if ratio was 1.5-2. MYC amplifications were correlated with clinicopathological details and OS.
Results
Currently 30 patients have been recruited to this ongoing study. Results for the first 14 patients are presented. Half the patients were male with a median age of 65 years. The majority (86%) were newly diagnosed. Most patients (86%) were ECOG 0, 1 or 2. ddPCR results revealed two patients had MYC-Lamplifications (ratios 2.98 and 9.95). One additional patient had borderline MYC-C amplification (ratio 1.83). Both patients with MYC-L amplified ctDNA presented with superior vena cava obstruction and were both T4N3 at time of diagnosis. Both are undergoing first-line chemotherapy and no radiological assessment has been performed to date.
Conclusions
SCLC has a dismal prognosis with a dire need to improve treatment options. We have high number of SCLC patients in our centre in Ireland. These patients can deteriorate quickly and become ineligible for clinical trials which require pre-screening. MYC amplification may not only offer prognostic information but is indirectly targetable, in addition to direct MYC inhibitors in development. Real time ddPCR of ctDNA in patient plasma is an effective, cost-efficient method for serum identification of MYC amplification with results available within 3-5 days of blood draw, permitting complex pre-screening in a timely manner to allow prognostication, trial recruitment and a future actionable mutation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Cork University Hospital.
Funding
Breakthrough Cancer research Charity, University College Cork.
Disclosure
H. Bye: Full/Part-time employment: AstraZeneca. A.R. Minchom: Honoraria (self), Advisory/Consultancy: Loxo Oncology; Honoraria (self), Advisory/Consultancy: Janssen Pharmaceuticals; Honoraria (self), Advisory/Consultancy: Faron Pharmaceuticals; Honoraria (self), Advisory/Consultancy: Bayer Pharmaceuticals; Honoraria (self), Advisory/Consultancy: Novartis Oncology; Honoraria (self), Advisory/Consultancy: Merck Pharmaceuticals. M. Hubank: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Guardant Health; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim. D. Collins: Honoraria (self): Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Genmab; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: Seattle Genetics. All other authors have declared no conflicts of interest.