1790P Clinical utility of ctDNA and CTCs for genomic profiling and monitoring chemotherapy response in patients with small cell lung cancer

Abstract

Circulating tumour cells (CTCs) counts and circulating tumour DNA (ctDNA) sequencing offer a reliable approach to monitor therapeutic efficacy in multiple solid tumours. This study evaluated the utility of ctDNA and CTCs to monitor efficacy of patients (pts) with SCLC. Pts included on the study had histologically or cytologically confirmed SCLC, and received first-line etoposide plus cisplatin (EP) chemotherapy every three weeks for 6 cycles. The primary endpoint was progression-free survival (PFS). Pre-treatment tumour biopsy specimens and longitudinal plasma samples were collected to perform next-generation sequencing and calculate the number of CTCs per 6ml peripheral blood. Molecular tumour burden index (mTBI) (in house) was used to reflect the longitudinal changes in overall molecular tumour burden. Between November 2018 and May 2020, 35 pts were enrolled, median follow-up duration was 10.3 (range 2.7-18) months. PFS was not reached. Investigator-assessed objective response rate (ORR) was 74.3% (95% CI, 59.1%-89.5%). Of 26 pts with available baseline tumour and blood samples, 78.2% (241/308) of tissue derived mutations were observed in ctDNA. The most frequently mutated genes were TP53 (92.3%), RB1 (50.0%) and LRP1B (42.3%) in ctDNA analysis, which were consistent with tissue analysis (96.2%, 53.8% and 38.5%, respectively). LRP1B mutation was more common in extensive stage (ES)-SCLC than in limited stage (LS)-SCLC (85.7% vs 23.5%, P=0.009). Longitudinal plasma samples from 16 pts were analysed, the median mTBI decreased from 8.3 (range 0.66-49.77) at baseline to 0.59 (range 0-1.58) after 2 cycles of treatment, the concordance rate between mTBI and imaging evaluation was 100%. While after 6 cycles of treatment, the median mTBI increased to 0.86 (range 0-32.34) - 8 pts increased and 8 pts kept declining. Six of the increased pts (6/8, 75%) were subsequently verified by imaging, one of the pts whose levels continued to decrease (1/8, 12.5%) had an imaging progressive disease (PD). Changes in CTCs were monitored in 10 pts: the median number of CTCs increased from 8.0 (range 1-22) at baseline to 9.5 (range 3-98) after 2 cycles of treatment, and then declined to 6.5 (range 1-25) after 6 cycles of chemotherapy, which was contrary to the results of the mTBI and imaging. ctDNA assessment is feasible for genomic profiling, therapy monitoring and early progression detection in SCLC, while assessment of CTCs needs more exploration.