In patients with locally advanced hepatocellular carcinoma (HCC), a personalized dosimetry approach targeting the index lesion was associated with greater improvements in response and survival vs standard dosimetry targeting the perfused lobe, according to findings from a phase 2 study published in the Lancet Gastroenterology and Hepatology.
The multicenter, open-label DOSISPHERE-01 trial (ClinicalTrials.gov Identifier: NCT02582034) included 60 adults with unresectable HCC who had a minimum of 1 measurable lesion 7 cm or greater in size, a hepatic reserve of at least 30% following selective internal radiation therapy (RT), no extrahepatic spread, and no contraindications to selective internal RT.
The study population included 60 patients who were randomly assigned to receive either standard dosimetry (120±20 Gy) targeted to the perfused lobe (n=29) or personalized dosimetry (≥205 Gy) targeted to the index lesion (n=31).
The primary end point was the investigator-assessed objective response rate in the index lesion (per European Association for the Study of Liver criteria) 3 months after selective internal RT in the modified intention-to-treat (ITT) population. Safety was assessed in all patients who received at least 1 selective internal RT injection.
The modified ITT population included 28 patients in each cohort. Results showed that a significantly greater proportion of patients in the personalized dosimetry group (71%; 95% CI, 51-87) had an objective response to therapy compared with patients in the standard dosimetry group (36% (95% CI, 19-56); P =.0074).
At a median follow-up of 27.2 months, the median overall survival (OS) was also found to favor the personalized dosimetry approach vs with the standard dosimetry method. The median OS was 26.6 months (95% CI, 11.7-not reached) in the experimental arm and 10.7 months (95% CI, 6.0-14.8) in the control arm. The hazard ratio was 0.38 (95% CI, 0.19-0.83; P =.0063).
In the safety analysis population, 20% of the 35 patients in the personalized dosimetry group and 33% of the 21 patients in the standard dosimetry group experienced a serious adverse event (AE) of any grade. Grade 3 or higher AEs were seen in 60% and 76% of patients who underwent personalized and standard dosimetry, respectively.
The most frequent grade 3 or higher AEs were ascites (3% for personalized dosimetry vs 10% for standard dosimetry), hepatic failure (6% vs 0%), lymphopenia (34% vs 43%), elevated aspartate aminotransferase concentrations (9% vs 10%), elevated alanine aminotransferase concentrations (9% vs 0%), anemia (6% vs 5%), gastrointestinal hemorrhage (0% vs 10%), and icterus (0% vs 10%). One treatment-related death occurred in each group.
Study limitations included the small number of patients as well as the lack of patients with lesions measuring less than 7 cm, which could affect the generalizability of the findings. In spite of the study’s limitations, the investigators concluded that their findings “challenge the interpretation of the previously published negative phase 3 trials of selective internal radiation therapy, in which personalized dosimetry was not used.” The data also underscore the need for further study of the personalized approach in late-stage trials of selective internal RT either alone or in combination with “newer agents.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of the authors’ disclosures.
Garin E, Tselikas L, Guiu B, et al; DOSISPHERE-01 Study Group. Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial. Lancet Gastroenterol Hepatol. Published online November 6, 2020. doi:10.1016/S2468-1253(20)30290-9