News
17th World Congress on Gastrointestinal Cancers
R Ian Lloyd/Masterfile/Corbis
Colorectal liver metastases
Published Online July 8, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)00137-0 The 17th World Congress on Gastrointestinal Cancers was held in Barcelona, Spain, on July 1–4, 2015
Guy van Hazel (Perth, Australia) presented data from the SIRFLOX trial, which compared first-line mFOLFOX6 with mFOLFOX6 and selective internal radiation therapy with Y-90 resin microspheres in patients with non-resectable liveronly or liver-dominant metastatic colorectal cancer. Bevacizumab could be used in both arms of the trial, at the discretion of the investigators. 263 patients were randomly assigned to receive mFOLFOX6 and 267 to receive mFOLFOX6 plus selective internal radiotherapy. After a median follow-up of 36·1 months, there was no difference between groups in progression-free survival (PFS)—the primary endpoint—median PFS was 10·2 months in the control group versus 10·7 months in the experimental group (hazard ratio [HR] 0·93, 95% CI 0·77–1·12; p=0·429). However, liver PFS (cumulative incidence of liver progression), a secondary outcome, was substantially better in the group who received radiotherapy: median liver PFS was 12·6 months in the control group versus 20·5 months in the experimental group (HR 0·69, 95% CI 0·55–0·90; p=0·002), driven by the subgroup of patients who had liver-only metastases. 1·9% of patients in the control group died versus 3·7% of those in the experimental group. The most common chemotherapyassociated toxicity of grade 3 or worse was neutropenia (28·5% vs 40·7%), while the most common grade 3 or worse adverse event associated with the selective internal radiotherapy was gastric or duodenal ulcers (none vs 3·7%). Patients remain in follow-up to determine if the benefit in local control will result in an overall survival benefit.
BRAF-mutant colorectal cancer Up to 10% of patients with colorectal cancer have BRAF V600E mutations, which are associated with poor prognosis. However, unlike in 890
BRAF-mutant melanoma, BRAF or MEK inhibitors have little activity in BRAFmutant colorectal cancer. Preclinical data suggests that inhibition of both the EGFR and MAPK pathways may be necessary to successfully treat this disease. Eric Van Cutsem (Leuven, Belgium) presented updated data from a phase 1/2 trial in which patients with BRAF-mutant metastatic colorectal cancer received either a doublet of the BRAF inhibitor dabrafenib and the anti-EGFR antibody panitumumab (20 patients received the full doublet dose), a doublet of the MEK inhibitor trametinib with panitumumab (13 received the full dose), or triplet therapy with all three drugs (35 patients, of whom 24 received the full dose). The most common adverse events were skin related, and mainly grade 1–2 in nature, although significant skin toxicity was noted with trametinib and panitumumab, and lower dose cohorts are now being explored. Two (10%, 95% CI 1·2–38·7) patients in the dabrafenib plus panitumumab group had an objective response, as did nine (26%, 12·5–43·3) who received the triplet, with longer duration of responses noted with the triplet. Translational studies showed that the triplet regimen inhibited the MAPK pathway more than either of the doublets, although still to a lesser extent than dabrafenib monotherapy in patients with melanoma. A further 60 patients are being recruited to receive the triplet regimen, with two different doses of panitumumab.
Immunotherapy in gastric cancer Y-J Bang (Seoul, South Korea) presented data for patients with recurrent or metastatic gastric cancer enrolled in the phase 1b KEYNOTE-012 study, which treated patients with the anti-PD-1 monoclonal antibody pembrolizumab. 39 patients were enrolled, with an objective response being noted in 22% (95% CI 10–39)
of the patients. The median duration of response was 40 weeks (range 20+ to 48+); 6-month PFS was 26% and 6-month overall survival was 66%. Grade 3–4 treatment-related adverse events were noted in 13% of patients, including fatigue, hypothyroidism, pneumonitis, pemphigoid, and peripheral sensory neuropathy. No differences in outcome were noted between patients enrolled in AsiaPacific and those enrolled elsewhere.
SENRI trial Aprepitant is recommended for the prevention of chemotherapyinduced nausea and vomiting for patients receiving highly emetogenic chemotherapy. Although FOLFOX and XELOX are deemed to be only moderately emetogenic, oxaliplatinbased chemotherapy in patients with metastatic colorectal cancer has been shown to be associated with high rates of nausea and vomiting in phase 3 trials. Thus, J Nishimura (Suita, Japan) and colleagues did the phase 3 SENRI trial, in which 413 patients with colorectal cancer who were due to undergo oxaliplatin-based chemotherapy were randomly assigned to receive either a 5-HT3-receptor antagonist and dexamethasone or the same regimen with aprepitant or fosaprepitant in the first cycle of chemotherapy. All patients received aprepitant or fosaprepitant in the second cycle of chemotherapy. The primary endpoint was the rate of patients with no emesis. Significantly more patients in the aprepitant group had no vomiting in both the overall and delayed phases than did those in the control group (95·7% vs 83·6% in the overall phase; 95·7% vs 84·7% in the delayed phase). There were no significant differences in adverse events between the two groups. Of note, substantially more women benefited from aprepitant-based treatment than did men.
Rob Brierley www.thelancet.com/oncology Vol 16 August 2015
17th World Congress on Gastrointestinal Cancers
R Ian Lloyd/Masterfile/Corbis
Colorectal liver metastases
Published Online July 8, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)00137-0 The 17th World Congress on Gastrointestinal Cancers was held in Barcelona, Spain, on July 1–4, 2015
Guy van Hazel (Perth, Australia) presented data from the SIRFLOX trial, which compared first-line mFOLFOX6 with mFOLFOX6 and selective internal radiation therapy with Y-90 resin microspheres in patients with non-resectable liveronly or liver-dominant metastatic colorectal cancer. Bevacizumab could be used in both arms of the trial, at the discretion of the investigators. 263 patients were randomly assigned to receive mFOLFOX6 and 267 to receive mFOLFOX6 plus selective internal radiotherapy. After a median follow-up of 36·1 months, there was no difference between groups in progression-free survival (PFS)—the primary endpoint—median PFS was 10·2 months in the control group versus 10·7 months in the experimental group (hazard ratio [HR] 0·93, 95% CI 0·77–1·12; p=0·429). However, liver PFS (cumulative incidence of liver progression), a secondary outcome, was substantially better in the group who received radiotherapy: median liver PFS was 12·6 months in the control group versus 20·5 months in the experimental group (HR 0·69, 95% CI 0·55–0·90; p=0·002), driven by the subgroup of patients who had liver-only metastases. 1·9% of patients in the control group died versus 3·7% of those in the experimental group. The most common chemotherapyassociated toxicity of grade 3 or worse was neutropenia (28·5% vs 40·7%), while the most common grade 3 or worse adverse event associated with the selective internal radiotherapy was gastric or duodenal ulcers (none vs 3·7%). Patients remain in follow-up to determine if the benefit in local control will result in an overall survival benefit.
BRAF-mutant colorectal cancer Up to 10% of patients with colorectal cancer have BRAF V600E mutations, which are associated with poor prognosis. However, unlike in 890
BRAF-mutant melanoma, BRAF or MEK inhibitors have little activity in BRAFmutant colorectal cancer. Preclinical data suggests that inhibition of both the EGFR and MAPK pathways may be necessary to successfully treat this disease. Eric Van Cutsem (Leuven, Belgium) presented updated data from a phase 1/2 trial in which patients with BRAF-mutant metastatic colorectal cancer received either a doublet of the BRAF inhibitor dabrafenib and the anti-EGFR antibody panitumumab (20 patients received the full doublet dose), a doublet of the MEK inhibitor trametinib with panitumumab (13 received the full dose), or triplet therapy with all three drugs (35 patients, of whom 24 received the full dose). The most common adverse events were skin related, and mainly grade 1–2 in nature, although significant skin toxicity was noted with trametinib and panitumumab, and lower dose cohorts are now being explored. Two (10%, 95% CI 1·2–38·7) patients in the dabrafenib plus panitumumab group had an objective response, as did nine (26%, 12·5–43·3) who received the triplet, with longer duration of responses noted with the triplet. Translational studies showed that the triplet regimen inhibited the MAPK pathway more than either of the doublets, although still to a lesser extent than dabrafenib monotherapy in patients with melanoma. A further 60 patients are being recruited to receive the triplet regimen, with two different doses of panitumumab.
Immunotherapy in gastric cancer Y-J Bang (Seoul, South Korea) presented data for patients with recurrent or metastatic gastric cancer enrolled in the phase 1b KEYNOTE-012 study, which treated patients with the anti-PD-1 monoclonal antibody pembrolizumab. 39 patients were enrolled, with an objective response being noted in 22% (95% CI 10–39)
of the patients. The median duration of response was 40 weeks (range 20+ to 48+); 6-month PFS was 26% and 6-month overall survival was 66%. Grade 3–4 treatment-related adverse events were noted in 13% of patients, including fatigue, hypothyroidism, pneumonitis, pemphigoid, and peripheral sensory neuropathy. No differences in outcome were noted between patients enrolled in AsiaPacific and those enrolled elsewhere.
SENRI trial Aprepitant is recommended for the prevention of chemotherapyinduced nausea and vomiting for patients receiving highly emetogenic chemotherapy. Although FOLFOX and XELOX are deemed to be only moderately emetogenic, oxaliplatinbased chemotherapy in patients with metastatic colorectal cancer has been shown to be associated with high rates of nausea and vomiting in phase 3 trials. Thus, J Nishimura (Suita, Japan) and colleagues did the phase 3 SENRI trial, in which 413 patients with colorectal cancer who were due to undergo oxaliplatin-based chemotherapy were randomly assigned to receive either a 5-HT3-receptor antagonist and dexamethasone or the same regimen with aprepitant or fosaprepitant in the first cycle of chemotherapy. All patients received aprepitant or fosaprepitant in the second cycle of chemotherapy. The primary endpoint was the rate of patients with no emesis. Significantly more patients in the aprepitant group had no vomiting in both the overall and delayed phases than did those in the control group (95·7% vs 83·6% in the overall phase; 95·7% vs 84·7% in the delayed phase). There were no significant differences in adverse events between the two groups. Of note, substantially more women benefited from aprepitant-based treatment than did men.
Rob Brierley www.thelancet.com/oncology Vol 16 August 2015
