by ecancer reporter Janet Fricker

Patients with metastatic colorectal cancer (mCRC) with greater baseline liver tumour burdens (≥12%) treated with mFOLFOX6 and selective internal radiation therapy (SIRT) SIR-Spheres Y-90 resin treatment achieved a greater depth of response (DpR) than those receiving chemotherapy alone, reported a study at the European Society of Medical Oncology’s Gastrointestinal Cancer meeting, 29 June to 2 July, Barcelona, Spain.

The new analysis of the phase III SIRFLOX study found no differences in DpR rates between the two treatment groups for patients with liver tumour burden (≤12%) at study entry.

SIRT, also known as radioembolisation, allows tumours to be selectively irradiated leaving healthy tissue relatively unaffected.

For the technique, tens of millions of Yttirum-90 labelled coated resin microspheres (Sirtex) are injected into the hepatic arterial supply of the liver via a catheter inserted into the femoral artery thorough an incision in the groin.

The spheres, which are 32 microns in diameter, deliver high doses of ionizing pure beta radiation to tumours.

In the SIRFLOX study between October 2006 and April 2013, 530 patients with previously untreated metastatic colorectal cancer were randomly assigned 1:1 to FOLFOX (±bev) plus SIRT (n=267) or FOLFOX (±bev) alone (n=263).

Results of the study, published in the Journal of Clinical Oncology this February, showed median PFS at any site was 10.7 months in the FOLFOX (±bev) plus SIRT arm versus 10.2 months in the the FOLFOX (±bev) only arm (HR 0.93, 95% CI, 0.77 to 1.12; P=0.43); and median PFS in the liver by competing risk analysis was 20.5 months in the  FOLFOX (±bev) plus SIRT arm versus 12.6 months in the FOLFOX (±bev) arm (HR 0.69, 95% CI, 0.55 to 0.90; P=.002).

Although SIRT did not influence PFS at any site, results showed a 7.9 month prolongation of PFS in the liver.

In the current analysis, Heinemann and colleagues developed the depth of response analysis (DpR) concept where a novel volumetric model was used to estimate each patient’s spherical liver tumour volume, based on the length of up to five target tumours.

DpR was then measured by tracking tumour shrinkage until it reached its lowest point, or ‘nadir’.

The investigators identified patients from the SIRTEX study who had baseline tumour loads ≥12% (n=245 patients) and those who had tumour loads ≤ 12% (n=239 patients).

Results showed for those patients with ≥12% tumour burden the depth of response was 77.5% for those receiving FOLFOX (±bev) SIRT compared to 57.2% for those receiving FOLFOX (±bev) (P=0.003).

Furthermore, time to ‘nadir’ was 196 days for those receiving FOLFOX (±bev) versus 298 for FOLFOX(±bev) SIRT (p≤0.001).

In contrast, for patients with ≤12% tumour burden the depth of response was 72.5% for those receiving FOLFOX (±bev) SIRT versus 80.6% for those receiving FOLFOX (±bev) (p=0.763).

Differences in PFS between the two treatment groups were also more marked for those with higher tumour burden.

For those with ≥12% tumour burden PFS was 27.2 months for FOLFOX(±bev) SIRT versus 13.1 months for FOLFOX(±bev) (HR 0.69, 95% CI 0.439-0.844, p=0.003). 

For those with ≤12% tumour burden PFs was 15.1 months for FOLFOX(±bev) SIRT versus 12.2 months for  FOLFOX(±bev) (HR 0.778 95% CI 0.571-1.060, p=0.112).

“The greater depth of response and time to maximal response following SIR-Spheres Y-90 resin microspheres, together with the prolonged PFS in the liver, are very encouraging and increase our anticipation for the survival data we hope to see in 2017,”  said Volker Heinemann, the study presenter, from the Ludwig-Maximillian University, Munich, Germany.

The study, he added, is the first in the history of metastatic colorectal cancer where the initial tumour burden has been factored in.

“It shows that initial tumour burden does play a role,” said Heinemann, speculating that the more evolved tumour vasculature found in larger metastases might enable SIRT microspheres to be more readily trapped.

Reference

1. Heinemann V, Hazel GA, Sharma NK et al. Evaluation of depth of response within a volumetric model in patients with metastatic colorectal cancer: Results of the SIRFLOX study. Annals of Oncology 2016; 27 (Suppl 2): Abs. 0-014.

2. Heinemann V, Stintzing S, Modest DP et al. Early tumour shrinkage (ETS) and depth of response (DpR) in the treatment of patients with metastatic colorectal cancer (mCRC). European Journal of Cancer 2015; 51: 1927-1936.