Pexastimogene devacirepvec (Pexa-Vec) is a vaccinia virus-based oncolytic immunotherapy designed to preferentially replicate in and destroy tumor cells while stimulating anti-tumor immunity by expressing GM-CSF. An earlier randomized Phase IIa trial in predominantly sorafenib-naïve hepatocellular carcinoma (HCC) demonstrated an overall survival (OS) benefit. This randomized, open-label Phase IIb trial investigated whether Pexa-Vec plus Best Supportive Care (BSC) improved OS over BSC alone in HCC patients who failed sorafenib therapy (TRAVERSE). 129 patients were randomly assigned 2:1 to Pexa-Vec plus BSC vs. BSC alone. Pexa-Vec was given as a single intravenous (IV) infusion followed by up to 5 IT injections. The primary endpoint was OS. Secondary endpoints included overall response rate (RR), time to progression (TTP) and safety. A high drop-out rate in the control arm (63%) confounded assessment of response-based endpoints. Median OS (ITT) for Pexa-Vec plus BSC vs. BSC alone was 4.2 and 4.4 months, respectively (HR, 1.19, 95% CI: 0.78-1.80; p = .428). There was no difference between the two treatment arms in RR or TTP. Pexa-Vec was generally well-tolerated. The most frequent Grade 3 included pyrexia (8%) and hypotension (8%). Induction of immune responses to vaccinia antigens and HCC associated antigens were observed. Despite a tolerable safety profile and induction of T cell responses, Pexa-Vec did not improve OS as second-line therapy after sorafenib failure. The true potential of oncolytic viruses may lie in the treatment of patients with earlier disease stages which should be addressed in future studies. ClinicalTrials.gov: NCT01387555 ARTICLE HISTORY

No abstract

Direct sequencing and reverse hybridization are currently the main methods for detecting drug-resistance mutations of hepatitis B virus (HBV). However, these methods do not enable haplotype analysis so they cannot be used to determine whether the mutations are co-located on the same viral genome. This limits the accurate identification of viral mutants that are resistant to drugs with a high genetic barrier. In our current study, ultra-deep pyrosequencing (UDPS) was used to detect HBV drug-resistance mutations in 25 entecavir-treated and five treatment-naive patients. Of the 25 entecavir-treated patients, 18 had experienced virological breakthrough and two exhibited reduced susceptibility to entecavir. The results obtained by UDPS were compared with those of direct sequencing, and the haplotypes of the drug-resistant HBV mutants were analysed. The average number of reads per patient covering the region in which drug-resistance mutations are located was 1735 (range 451-4526). UDPS detected additional drug-resistance mutations not detected by direct sequencing in 19 patients (mutation frequency range 1.1-23.8%). Entecavir-resistance mutations were found to be co-located on the same viral genome in all 20 patients displaying virological breakthrough or reduced susceptibility to entecavir. In conclusion, UDPS was not only sensitive and accurate in identifying drug-resistance mutations of HBV but also enabled haplotype analysis of the mutants. This method may offer significant advantages in explaining and predicting the responses of patients with HBV to antiviral therapy.

No abstract

No abstract

Background: In the phase III RESORCE trial, regorafenib improved overall survival (OS) vs placebo in pts with uHCC who progressed on sorafenib. The international, prospective REFINE study was designed to evaluate regorafenib in pts with uHCC in routine practice. We present interim results for pts enrolled in REFINE in Korea, China, and Taiwan. Methods: REFINE is an ongoing observational study that recruited patients with uHCC for whom a decision to treat with regorafenib was made by the treating physician prior to enrollment according to the local health authority approved label. A planned interim analysis was performed when the first 500 pts in the global cohort had been observed for 4 months. The primary aim is to assess treatment-emergent adverse events (TEAEs; NCI-CTCAE v4.03). Secondary endpoints include OS, progression-free survival, and tumor response. Tumor response and progression are assessed per investigator according to local standard. abstracts Annals of Oncology Volume 31 -Issue S4 -2020 S699

No abstract

No abstract