by ecancer reporter Janet Fricker

Patients with advanced or inoperable Hepatocellular Carcinoma (HCC) treated with Selective Internal Radiation Therapy (SIRT) had better tumour response rates and significantly fewer adverse events than patients treated with the standard of care sorafenib, found the SIRveNIB study.

The investigator-led study, presented at ASCO 2017 (Chicago June 2-6, 2017), found no difference for the primary endpoint of overall survival (OS) between the two groups.

“The comparative data on side effects reported in the SIRveNIB study unequivocally favoured Y-90 resin microspheres over sorafenib,” said Professor Pierce Chow, the study presenter from the National Cancer Centre Singapore.

“Based on this study clinicians can decide what to do with patients with advanced HCC who have very short lives.”
SIRT is a form of internal radiation therapy involving Y-90 resin microspheres, with median diameters of 32.5 microns, delivered directly to inoperable liver tumours via the hepatic artery.

The resin microspheres, which emit beta radiation penetrating an average of 2.5 mm is tissue, lodge preferentially in microvasculature surrounding tumours, thereby minimizing normal liver effects.

SIRT involves one to two treatments, while the multi-kinase inhibitor sorafenib (currently the only approved systemic treatment for advanced liver cancer) involves twice daily tablets. 

For the SIRveNIB study, The Asia-Pacific Hepatocellular Carcinoma Trials Group randomized 360 patients with locally advanced HCC not amenable to curative treatment 1:1  to receive assessment for SIRT suitability  (n=182)  or sorafenib 400 mg BID (n=178).
Treated patients included 130 in the SIRT arm and 162 in the sorafenib arm.

Notably, for SIRT the median time from randomisation to treatment was 21 days compared to three days in the sorafenib arm and furthermore 52 patients in the SIRT arm did not receive allocated treatment.

The study was undertaken at 27 centres across 11 countries in Asia Pacific.

Results for the intent-to-treat population showed median OS  was 8.84 months for SIRT patients versus 10.02 months for sorafenib patients (HR 1.12 (95% CI 0.88 to 1.42); P=0.360.)

The median OS for the treated population was 11.27 months for SIRT patients versus 10.41 months for sorafenib patients (HR 0.86 (95% CI 0.66 to 1.13); P=0.273.)

For the treated population the tumour response rate was 23.1% for patients receiving SIRT versus 1.9% for patients receiving sorafenib (P<.001).

Results showed that 84.6% of patients in the sorafenib arm experienced at least one adverse event versus 60.0% in the SIRT arm (P<.0001) and that serious adverse events were reported in 35.2% of patients in the sorafenib arm versus 20.8% of patients in the SIRT arm (P=0.0091).
Patients treated with SIRT reported less fatigue, diarrhoea, hand-foot skin reactions, alopecia, and hypertension than patients treated with sorafenib.

The discussant  Robin Kate Kelley, from UCSF Medical Center, San Francisco, said, “In the changing landscape of HCC SIRT warrants further studies in sequence or combination with new therapies.

“There is certainly a role for SIRT in patients who may not be candidates for sorafenib due to advanced toxicity.”

Notably, said Prof. Chow, the findings of the SIRveNIB mirror the findings of the 459-patient French SARAH study reported by Valerie Vilgrain at the 2017 International Liver Congress™ in Amsterdam, The Netherlands in April.

“French patients get HCC from alcohol and hepatitis C, while Asian Pacific patients get HCC from hepatitis B.

“The fact that the two studies essentially go in the same direction shows that SIRT can be effective across a whole range of patients with primary HCC,” said Professor Chow.

At his own centre, Professor Chow added that he had been able to resect around 10% of patients who had received SIRT. However, he added, that in Asia Pacific there are only three or four centres with surgical teams able to undertake such procedures.

• In a separate study, Professor Ricky Sharma, from University College, London, presented results of the FOXFIRE Combined analysis involving 1,103 patients randomised to receive either standard first-line chemotherapy for colorectal cancer that has spread to the liver or chemotherapy plus SIRT.

The analysis combined data from three studies:  the SIRFLOX study (first presented in 2015) and two new studies, FOXFIRE and FOXFIRE global.

The studies took place across 14 centres.

While no significant difference was found in OS between the groups (HR 1.04; (95% CI: 0.90-1.19) p=0.609) or progression free survival (HR 0.90; (95% CI: 0.79-1.02) p=0.108); a significantly higher tumour objective response rate occurred among patients treated with SIRT (p=0.001).

“Our assumption has always been that if you improve control in the liver you should improve overall survival.

“But it is often difficult to see statistically significant results when patients like the ones we treated have received multiple lines of therapy after they receive the new treatment,” said Professor Sharma.

Of note, was the combined exploratory subgroup analysis  in 179  patients with right-sided primary tumours where investigators showed SIRT increased median overall survival by 4.9 months and reduced risk of death at any time point by 36% (HR 0.64; 95% CI 0.46 to 0.89; p=0.007).

“Patients with right-sided primary colon tumours represent more than a third of all colon cancer patients.

“We know that right sided tumours don’t do as well and that their genetic phenotype is different from left sided tumours.

“Perhaps we are seeing that non cytotoxic therapies show greater effects in such patients,” said Professor Sharma.

Reference
Chow PKH, et al.  Phase III multi-centre open-label randomized controlled trial of selective internal radiation therapy (SIRT) versus sorafenib in locally advanced hepatocellular carcinoma: The SIRveNIB study.  ASCO Annual Meeting, J Clin Oncol 2017; 35 (Suppl): Abs 4002

Sharma R, et al. Overall survival analysis of the FOXFIRE prospective randomized studies of first-line selective internal radiotherapy (SIRT) in patients with liver metastases from colorectal cancer. ASCO Annual Meeting, J Clin Oncol 2017; 35 (Suppl): Abs 3507