Randomised Phase 1b/2 trial of tepotinib vs sorafenib in Asian patients with advanced hepatocellular carcinoma with MET overexpression.

BACKGROUND: This open-label, Phase 1b/2 study evaluated the highly selective MET inhibitor tepotinib in systemic anticancer treatment (SACT)-naive Asian patients with advanced hepatocellular carcinoma (aHCC) with MET overexpression. METHODS: In Phase 2b, tepotinib was orally administered once daily (300, 500 or 1,000 mg) to Asian adults with aHCC. The primary endpoints were dose-limiting toxicities (DLTs) and adverse events (AEs). Phase 2 randomised SACT-naive Asian adults with aHCC with MET overexpression to tepotinib (recommended Phase 2 dose [RP2D]) or sorafenib 400 mg twice daily. The primary endpoint was independently assessed time to progression (TTP). RESULTS: In Phase 1b (n = 27), no DLTs occurred; the RP2D was 500 mg. In Phase 2 (n = 90, 45 patients per arm), the primary endpoint was met: independently assessed TTP was significantly longer with tepotinib versus sorafenib (median 2.9 versus 1.4 months, HR = 0.42, 90% confidence interval: 0.26-0.70, P = 0.0043). Progression-free survival and objective response also favoured tepotinib. Treatment-related Grade ≥3 AE rates were 28.9% with tepotinib and 45.5% with sorafenib. CONCLUSIONS: Tepotinib improved TTP versus sorafenib and was generally well tolerated in SACT-naive Asian patients with aHCC with MET overexpression. TRIAL REGISTRATION: ClinicalTrials.gov NCT01988493.

Effect of interleukin-1beta and glutathione S-transferase genotypes on the development of gastric mucosa-associated lymphoid tissue lymphoma.

e tested whether polymorphic variations in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and interleukin-1 (IL-1beta and IL-1RN) genes confer susceptibility to mucosa-associated lymphoid tissue lymphomas (MALT) in a Chinese population. The rates of GSTM1, GSTP1, IL-1beta and IL-1RN genotypes did not differ between patients and controls. However, GSTT1 null genotypes were significantly more common in patients with MALT lymphomas (43/75 vs. 138/321, p=0.029; OR=1.8, 95% CI: 1.1-3.0) than in controls. Our results suggest that a glutathione S-transferase defect plays a role in MALT lymphoma.

Epidemiology of multiple myeloma in Taiwan: increasing incidence for the past 25 years and higher prevalence of extramedullary myeloma in patients younger than 55 years.

BACKGROUND: The incidence of multiple myeloma (MM) is lower in Asia than in western countries. However, no data are available on descriptive epidemiology of MM in Chinese. METHODS: From 1979 to 2003, 3602 MM patients were registered in the Taiwan National Cancer Registry. The annual incidence and mortality were calculated and age-standardized to the world standard population in the year 2000. Age-period-cohort effects on incidence were analyzed. The salient clinical data of 526 MM patients in a single institute were also investigated. RESULTS: From 1979 to 2003, the average age-adjusted incidence per 100,000 population was 0.75. The incidence increased with age to a peak of 5.2 in those aged 75-79 years. In addition to age, remarkable period and birth cohort effects were found to contribute to increased incidence of MM. The age-adjusted mortality also increased, which accounted for an average of 0.59 per 100,000 deaths; however, the fatality rate was steady at 80%. Clinical and laboratory characteristics and treatment outcomes of the 526 MM patients were similar to those reported elsewhere. Remarkably, extramedullary myeloma (extra-MM) at diagnosis was more common in patients younger than 55 years of age than in others (43% vs 13%, P < .001). CONCLUSIONS: Incidence of MM in Taiwan has dramatically increased in recent years and is associated with a birth-cohort effect. There are no apparent differences in treatment outcome between MM patients in Taiwan and in other countries. However, prevalence of extra-MM is higher in patients younger than 55 years of age.