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Research in brief
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Research in brief
Miriam Maslo/Science Photo Library
Local excision for rectal carcinoma
For the GRECCAR 2 trial see Articles Lancet 2017; published online June 7. http://dx.doi. org/10.1016/S01406736(17)31056-5 For the POLARIS trials see N Engl J Med 2017; 376: 2134–46 For the TURANDOT trial see Articles Lancet 2017; published online May 17. http://dx.doi. org/10.1016/S01406736(17)30930-3 For the FMT trial see Hepatology 2017; published online June 6. DOI:10.1002/hep.29306 For the adolescent HCV trial see Hepatology 2017; published online May 22. DOI:10.1002/ hep.29278
Organ preservation by local excision is not superior to total mesorectal excision in patients with lower rectal cancers after good response t o c h e m o r a d i o t h e r a py, t h e GRECCAR 2 trial suggests. However, better patient selection could improve the strategy. Eric Rullier and colleagues randomly assigned patients aged 18 years and older with stage T2–T3 lower rectal carcinoma and who had a good clinical response to neoadjuvant chemoradiotherapy to local excision (n=74) or total mesorectal excision group (n=71). In the local excision group, 26 patients underwent completion total mesorectal excision. The primary endpoint was a composite outcome of death, recurrence, major surgical morbidity, and side-effects at 2 years after surgery. In the modified ITT population, one or more of these events occurred in 41 (56%) of 73 patients in the local excision group and 33 (48%) of 69 in the total mesorectal excision group (odds ratio 1·33, 95% CI 0·62–2·86; p=0·43).
Three drug combination for HCV
Patients infected with hepatitis C virus (HCV) for whom treatment with a direct-acting antiviral agent (DAA) regimen has previously failed could have a new salvage option, two phase 3 trials suggest. In POLARIS-1, Marc Bourlière and colleagues randomly assigned patients with HCV genotype 1 infection who had previously been treated with an NS5A inhibitor to receive either sofosbuvir–velpatasvir–voxilaprevir (n=150) or placebo (n=150) once daily for 12 weeks. Patients with other HCV genotypes (n=114) were enrolled in the sofosbuvir– velpatasvir–voxilaprevir group. POLARIS-4 included patients with
552
HCV genotype 1, 2, or 3 who had previously been treated with a DAA but not an NS5A inhibitor. Patients were randomly assigned to receive sofosbuvir–velpatasvir– voxilaprevir (n=163) or sofosbuvir– velpatasvir (n=151) for 12 weeks. An additional 19 patients with HCV genotype 4 infection were enrolled in the sofosbuvir–velpatasvir– voxilaprevir group. In POLARIS-1, the rate of sustained virological response (SVR) at week 12 was 96% with sofosbuvir–velpatasvir–voxilaprevir and 0% with placebo. In POLARIS-4, the rate of response was 98% with the triple drug regimen and 90% with two-drug therapy.
TURANDOT trial
The anti-MAdCAM antibody PF-00547659 demonstrates signifi cantly increased remission in patients with moderate-to-severe ulcerative colitis who had failed or were intolerant to at least one conventional therapy. Séverine Vermeire and colleagues randomly assigned patients to receive PF-00547659 at doses of 7·5 mg (n=71), 22·5 mg (n=72), 75 mg (n=71), or 225 mg (n=70) or placebo (n=73). Remission rates at week 12 (the primary endpoint) were highest in patients in the PF-00547659 22·5 mg group (16·7% [12 of 72]) and 75 mg group (15·5% [11 of 71]), and were significantly greater than placebo in three of the four treatment groups. PF-00547659 was well tolerated in this patient population; however, due to the short duration of this trial, safety data should be interpreted with caution.
FMT for hepatic encephalopathy
Fecal microbiota transplantation (FMT) using a rationally derived stool donor is safe for patients with cirrhosis and recurrent hepatic
encephalopathy, and is associated with reduced hospitalisations and improved cognitive impairment caused by severe liver disease. Jasmohan Bajaj and colleagues randomly assigned patients to receive 5 days of broad-spectrum antibiotic pre-treatment followed by a single FMT enema from the same donor (n=10) or to standard of care alone (n=10). The primary endpoint was safety; eight (80%) of the standard of care participants had a total of 11 serious adverse events compared with two (20%) in the FMT group (both FMT-unrelated; p=0·02). Five patients in the standard of care group developed further hepatic encephalopathy, compared with none in the FMT group (p=0·03). There was significant cognitive improvement in the FMT group compared with the standard of care group. The MELD score significantly increased following treatment with antibiotics but returned to baseline following FMT.
DAAs for adolescents with HCV
Sofosbuvir and ribavirin could be recommended for adolescents aged 12–17 with chronic HCV genotype 2 or 3, a new study suggests. Stefan Wirth and colleagues enrolled 52 patients to receive sofosbuvir 400 mg once daily and weight-based ribavirin twice daily for 12 weeks (genotype 2) or 24 weeks (genotype 3). SVR12 was achieved in 98% (95% CI 90–100) of patients (51 of 52); SVR12 was 100% (13 of 13) for patients with genotype 2 and 97% (38 of 39) for patients with genotype 3. The one patient who did not achieve this was lost to follow-up after achieving an SVR at week 4. The most commonly reported adverse events were nausea (27%) and headache (23%).
Holly Baker
www.thelancet.com/gastrohep Vol 2 August 2017
Research in brief
Miriam Maslo/Science Photo Library
Local excision for rectal carcinoma
For the GRECCAR 2 trial see Articles Lancet 2017; published online June 7. http://dx.doi. org/10.1016/S01406736(17)31056-5 For the POLARIS trials see N Engl J Med 2017; 376: 2134–46 For the TURANDOT trial see Articles Lancet 2017; published online May 17. http://dx.doi. org/10.1016/S01406736(17)30930-3 For the FMT trial see Hepatology 2017; published online June 6. DOI:10.1002/hep.29306 For the adolescent HCV trial see Hepatology 2017; published online May 22. DOI:10.1002/ hep.29278
Organ preservation by local excision is not superior to total mesorectal excision in patients with lower rectal cancers after good response t o c h e m o r a d i o t h e r a py, t h e GRECCAR 2 trial suggests. However, better patient selection could improve the strategy. Eric Rullier and colleagues randomly assigned patients aged 18 years and older with stage T2–T3 lower rectal carcinoma and who had a good clinical response to neoadjuvant chemoradiotherapy to local excision (n=74) or total mesorectal excision group (n=71). In the local excision group, 26 patients underwent completion total mesorectal excision. The primary endpoint was a composite outcome of death, recurrence, major surgical morbidity, and side-effects at 2 years after surgery. In the modified ITT population, one or more of these events occurred in 41 (56%) of 73 patients in the local excision group and 33 (48%) of 69 in the total mesorectal excision group (odds ratio 1·33, 95% CI 0·62–2·86; p=0·43).
Three drug combination for HCV
Patients infected with hepatitis C virus (HCV) for whom treatment with a direct-acting antiviral agent (DAA) regimen has previously failed could have a new salvage option, two phase 3 trials suggest. In POLARIS-1, Marc Bourlière and colleagues randomly assigned patients with HCV genotype 1 infection who had previously been treated with an NS5A inhibitor to receive either sofosbuvir–velpatasvir–voxilaprevir (n=150) or placebo (n=150) once daily for 12 weeks. Patients with other HCV genotypes (n=114) were enrolled in the sofosbuvir– velpatasvir–voxilaprevir group. POLARIS-4 included patients with
552
HCV genotype 1, 2, or 3 who had previously been treated with a DAA but not an NS5A inhibitor. Patients were randomly assigned to receive sofosbuvir–velpatasvir– voxilaprevir (n=163) or sofosbuvir– velpatasvir (n=151) for 12 weeks. An additional 19 patients with HCV genotype 4 infection were enrolled in the sofosbuvir–velpatasvir– voxilaprevir group. In POLARIS-1, the rate of sustained virological response (SVR) at week 12 was 96% with sofosbuvir–velpatasvir–voxilaprevir and 0% with placebo. In POLARIS-4, the rate of response was 98% with the triple drug regimen and 90% with two-drug therapy.
TURANDOT trial
The anti-MAdCAM antibody PF-00547659 demonstrates signifi cantly increased remission in patients with moderate-to-severe ulcerative colitis who had failed or were intolerant to at least one conventional therapy. Séverine Vermeire and colleagues randomly assigned patients to receive PF-00547659 at doses of 7·5 mg (n=71), 22·5 mg (n=72), 75 mg (n=71), or 225 mg (n=70) or placebo (n=73). Remission rates at week 12 (the primary endpoint) were highest in patients in the PF-00547659 22·5 mg group (16·7% [12 of 72]) and 75 mg group (15·5% [11 of 71]), and were significantly greater than placebo in three of the four treatment groups. PF-00547659 was well tolerated in this patient population; however, due to the short duration of this trial, safety data should be interpreted with caution.
FMT for hepatic encephalopathy
Fecal microbiota transplantation (FMT) using a rationally derived stool donor is safe for patients with cirrhosis and recurrent hepatic
encephalopathy, and is associated with reduced hospitalisations and improved cognitive impairment caused by severe liver disease. Jasmohan Bajaj and colleagues randomly assigned patients to receive 5 days of broad-spectrum antibiotic pre-treatment followed by a single FMT enema from the same donor (n=10) or to standard of care alone (n=10). The primary endpoint was safety; eight (80%) of the standard of care participants had a total of 11 serious adverse events compared with two (20%) in the FMT group (both FMT-unrelated; p=0·02). Five patients in the standard of care group developed further hepatic encephalopathy, compared with none in the FMT group (p=0·03). There was significant cognitive improvement in the FMT group compared with the standard of care group. The MELD score significantly increased following treatment with antibiotics but returned to baseline following FMT.
DAAs for adolescents with HCV
Sofosbuvir and ribavirin could be recommended for adolescents aged 12–17 with chronic HCV genotype 2 or 3, a new study suggests. Stefan Wirth and colleagues enrolled 52 patients to receive sofosbuvir 400 mg once daily and weight-based ribavirin twice daily for 12 weeks (genotype 2) or 24 weeks (genotype 3). SVR12 was achieved in 98% (95% CI 90–100) of patients (51 of 52); SVR12 was 100% (13 of 13) for patients with genotype 2 and 97% (38 of 39) for patients with genotype 3. The one patient who did not achieve this was lost to follow-up after achieving an SVR at week 4. The most commonly reported adverse events were nausea (27%) and headache (23%).
Holly Baker
www.thelancet.com/gastrohep Vol 2 August 2017