SIRT plus FOLFOX chemo for mCRC improved progression-free survival in liver only

The addition of selective internal radiation therapy (SIRT) to FOLFOX-based first-line chemotherapy in patients with metastatic colorectal cancer (mCRC) failed to improve progression-free survival (PFS) at any site, but significantly improved median PFS in the liver, according to results of SIRFLOX, the first large, randomized controlled trial of liver-directed therapy in mCRC.

Median PFS at any site was similar for the SIRT and control arms at 10.7 and 10.2 months, respectively (hazard ratio, 0.93; 95% confidence interval, 0.77-1.12; P = .43). Median PFS in the liver was significantly greater in the SIRT than the control arm: 20.5 vs. 12.6 months (HR, 0.69; 95% CI, 0.55-0.90; P = .002) (J Clin Oncol. 2016 Feb 22. doi: 10.1200/JCO.2015.66.1181).

Fewer SIRT patients had the first disease progression occur in the liver (SIRT: 52.4%, control: 77%; P less than .001), and a correspondingly higher proportion of the SIRT arm had first progression outside the liver (SIRT: 27.7%, control 7.9%; P less than .001).

“Whereas control of intra- and extrahepatic disease is required to achieve a benefit in PFS at any site, the analysis of first progression site suggests that progressive disease in nonliver sites … may mitigate the benefit of controlling liver disease with SIRT. Furthermore, the appearance of new lesions accounted for a substantially greater proportion of first progressions in the liver in SIRT,” wrote Dr. Guy van Hazel of the University of Western Australia, and his colleagues.

To determine whether control of liver metastasis translates into survival gains, analysis of overall survival data from SIRFLOX combined with two other first-line studies are ongoing.

Only 84% of patients assigned to the SIRT arm received SIRT per protocol, which may have compromised the observed affect of SIRT on PFS at any site, according to investigators. In addition, a larger than expected number of patients (about 45%) had an intact primary tumor, which has an uncertain impact on PFS at any site but is reported to be associated with poorer survival.

Adverse events (AEs) were increased in the SIRT arm, both those associated with chemotherapy (for example, neutropenia, febrile neutropenia, and thrombocytopenia) and AEs associated with SIRT (for example, nausea, vomiting, abdominal pain, and fatigue).

In total, 530 chemotherapy-naïve patients with adenocarcinoma of the colon or rectum and proven liver metastases were enrolled in the randomized, controlled phase III SIRFLOX from 2006 to 2013. The control arm included 263 patients who received modified FOLFOX (mFOLFOX6), and the treatment arm included 267 patients who received mFOLFOX6 plus SIRT. Bevacizumab combined with mFOLFOX6 was allowed at the investigator’s discretion.*

*A change was made to this story on 2/25.

The addition of selective internal radiation therapy (SIRT) to FOLFOX-based first-line chemotherapy in patients with metastatic colorectal cancer (mCRC) failed to improve progression-free survival (PFS) at any site, but significantly improved median PFS in the liver, according to results of SIRFLOX, the first large, randomized controlled trial of liver-directed therapy in mCRC.

Median PFS at any site was similar for the SIRT and control arms at 10.7 and 10.2 months, respectively (hazard ratio, 0.93; 95% confidence interval, 0.77-1.12; P = .43). Median PFS in the liver was significantly greater in the SIRT than the control arm: 20.5 vs. 12.6 months (HR, 0.69; 95% CI, 0.55-0.90; P = .002) (J Clin Oncol. 2016 Feb 22. doi: 10.1200/JCO.2015.66.1181).

Fewer SIRT patients had the first disease progression occur in the liver (SIRT: 52.4%, control: 77%; P less than .001), and a correspondingly higher proportion of the SIRT arm had first progression outside the liver (SIRT: 27.7%, control 7.9%; P less than .001).

“Whereas control of intra- and extrahepatic disease is required to achieve a benefit in PFS at any site, the analysis of first progression site suggests that progressive disease in nonliver sites … may mitigate the benefit of controlling liver disease with SIRT. Furthermore, the appearance of new lesions accounted for a substantially greater proportion of first progressions in the liver in SIRT,” wrote Dr. Guy van Hazel of the University of Western Australia, and his colleagues.

To determine whether control of liver metastasis translates into survival gains, analysis of overall survival data from SIRFLOX combined with two other first-line studies are ongoing.

Only 84% of patients assigned to the SIRT arm received SIRT per protocol, which may have compromised the observed affect of SIRT on PFS at any site, according to investigators. In addition, a larger than expected number of patients (about 45%) had an intact primary tumor, which has an uncertain impact on PFS at any site but is reported to be associated with poorer survival.

Adverse events (AEs) were increased in the SIRT arm, both those associated with chemotherapy (for example, neutropenia, febrile neutropenia, and thrombocytopenia) and AEs associated with SIRT (for example, nausea, vomiting, abdominal pain, and fatigue).

In total, 530 chemotherapy-naïve patients with adenocarcinoma of the colon or rectum and proven liver metastases were enrolled in the randomized, controlled phase III SIRFLOX from 2006 to 2013. The control arm included 263 patients who received modified FOLFOX (mFOLFOX6), and the treatment arm included 267 patients who received mFOLFOX6 plus SIRT. Bevacizumab combined with mFOLFOX6 was allowed at the investigator’s discretion.*

*A change was made to this story on 2/25.

The addition of selective internal radiation therapy (SIRT) to FOLFOX-based first-line chemotherapy in patients with metastatic colorectal cancer (mCRC) failed to improve progression-free survival (PFS) at any site, but significantly improved median PFS in the liver, according to results of SIRFLOX, the first large, randomized controlled trial of liver-directed therapy in mCRC.

Median PFS at any site was similar for the SIRT and control arms at 10.7 and 10.2 months, respectively (hazard ratio, 0.93; 95% confidence interval, 0.77-1.12; P = .43). Median PFS in the liver was significantly greater in the SIRT than the control arm: 20.5 vs. 12.6 months (HR, 0.69; 95% CI, 0.55-0.90; P = .002) (J Clin Oncol. 2016 Feb 22. doi: 10.1200/JCO.2015.66.1181).

Fewer SIRT patients had the first disease progression occur in the liver (SIRT: 52.4%, control: 77%; P less than .001), and a correspondingly higher proportion of the SIRT arm had first progression outside the liver (SIRT: 27.7%, control 7.9%; P less than .001).

“Whereas control of intra- and extrahepatic disease is required to achieve a benefit in PFS at any site, the analysis of first progression site suggests that progressive disease in nonliver sites … may mitigate the benefit of controlling liver disease with SIRT. Furthermore, the appearance of new lesions accounted for a substantially greater proportion of first progressions in the liver in SIRT,” wrote Dr. Guy van Hazel of the University of Western Australia, and his colleagues.

To determine whether control of liver metastasis translates into survival gains, analysis of overall survival data from SIRFLOX combined with two other first-line studies are ongoing.

Only 84% of patients assigned to the SIRT arm received SIRT per protocol, which may have compromised the observed affect of SIRT on PFS at any site, according to investigators. In addition, a larger than expected number of patients (about 45%) had an intact primary tumor, which has an uncertain impact on PFS at any site but is reported to be associated with poorer survival.

Adverse events (AEs) were increased in the SIRT arm, both those associated with chemotherapy (for example, neutropenia, febrile neutropenia, and thrombocytopenia) and AEs associated with SIRT (for example, nausea, vomiting, abdominal pain, and fatigue).

In total, 530 chemotherapy-naïve patients with adenocarcinoma of the colon or rectum and proven liver metastases were enrolled in the randomized, controlled phase III SIRFLOX from 2006 to 2013. The control arm included 263 patients who received modified FOLFOX (mFOLFOX6), and the treatment arm included 267 patients who received mFOLFOX6 plus SIRT. Bevacizumab combined with mFOLFOX6 was allowed at the investigator’s discretion.*

*A change was made to this story on 2/25.