Circulating tumour DNA (ctDNA) in patients with metastatic colorectal cancer (mCRC): Prognostic significance and early changes during chemotherapy — ASN Events
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Circulating tumour DNA (ctDNA) in patients with metastatic colorectal cancer (mCRC): Prognostic significance and early changes during chemotherapy (#21)

Jeanne Tie 1 2 3 , Kinde Isaac 4 , Hui-Li Wong 1 2 5 , Joseph McKendrick 5 , Luis Diaz 4 , Nicholas Papadopoulos 4 , Madhu Singh 6 , Christos Karapetis 7 8 , Jayesh Desai 1 2 , Ben Tran 1 2 3 , Justin Roebert 9 , Robert Strausberg 10 , Kenneth Kinzler 4 , Bert Vogelstein 4 , Peter Gibbs 1 2 3 11
  1. Royal Melbourne Hospital, Parkville, VIC, Australia
  2. Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
  3. Western Hospital, Melbourne, Victoria, Australia
  4. Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, USA
  5. Eastern Health, Melbourne, Victoria, Australia
  6. Andrew Love Cancer Centre, Geelong, Victoria, Australia
  7. Flinders Medical Centre, Adelaide, South Australia, Australia
  8. Flinders University, Adelaide, South Australia, Australia
  9. MIA Victoria, Melbourne, Victoria, Australia
  10. Ludwig Institute for Cancer Research, New York, USA
  11. BioGrid Australia, Melbourne, Victoria, Australia

Background/Aims:  Prognostic and predictive biomarkers in mCRC are urgently needed. Analysis of ctDNA has shown promise as a liquid biopsy, reflecting the evolving mutational status of the tumor. Here we explored baseline ctDNA as a prognostic marker, and early changes in ctDNA as a marker of chemotherapy response.

Methods:  Serial plasma samples and CEA were collected at baseline, day 3 (D3) and cycle 2 day 1 (C2D1) from 40 mCRC patients receiving standard combination chemotherapy. Restaging scans performed at 8 weeks were centrally assessed using RECIST criteria. Samples were analysed at Johns Hopkins Kimmel Cancer Center. Tumour tissue was analysed for hotspot mutations in TP53, APC, KRAS, BRAF, PIK3CA, FBXW7 and SMAD4. The same mutation was queried and quantified in plasma using a massively parallel sequencing platform (Safe-SeqS).

Results:  Preliminary data is available on 31 patients in this ongoing study. At least 1 mutation was found in 30 of 31 (97%) tumours, with matching ctDNA found in 28 of 30 patients (93%). Median baseline cell-free DNA (cfDNA) and ctDNA levels were 8.6 ng/ml (0.7-168.7) and 238 copies/ml (0–27778), respectively. Patients with baseline cfDNA of ≥35 compared with <35 had shorter median overall survival (OS; 6.1 months v undefined, p=0.0009), with a trend for shorter progression-free survival (PFS; 3.6 v 7 months, p=0.1198). Baseline ctDNA of ≥300 copies/ml was associated with an inferior overall survival (OS; 6.9 v 16.0 months, p=0.0199). Patients with ≥20% compared with <20% reduction in tumour size at 8 weeks experienced a greater decrease in ctDNA from baseline to C2D1 (median decrease: 93% v 63%, p=0.0354).

Conclusion: ctDNA was detected in the great majority of patients with mCRC. cfDNA and ctDNA are promising markers of prognosis. Early changes in ctDNA levels may be a useful marker of tumour response.