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At this year's annual meeting of the American Society of Clinical Oncology (ASCO 2014), held May 30 through June 3 in Chicago, specialists discussed the latest cancer research. The editors of NEJM Journal Watch Oncology and Hematology were on hand to cover key presentations at the conference. Here, David Ilson, MD, PhD, reviews new findings in gastrointestinal cancer.
Venook and colleagues reported results of the randomized, phase III CALGB 80405 trial of first-line chemotherapy with either bevacizumab or cetuximab in patients with exon 12 and 13 KRAS wild-type metastatic colorectal cancer (abstract LBA3). More than 1100 patients were treated with physician choice of FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) or FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) chemotherapy. Most patients were male (60%–62%), most received FOLFOX (73%–74%), and 27%–28% had the primary tumor still in place.
Overall survival (OS; the primary endpoint) was similar with bevacizumab or cetuximab (29.0 and 29.9 months, respectively), as was progression-free survival (PFS; 10.8 vs 10.4 months). Outcomes also did not differ by chemotherapy with FOLFOX plus bevacizumab or cetuximab (OS, 26.6 and 30.1 months, respectively) or with FOLFIRI plus bevacizumab or cetuximab (OS, 33.4 and 28.9 months).
These results suggest that bevacizumab and cetuximab represent equivalent first-line options with chemotherapy in patients with exon 12 and 13 KRAS wild-type colorectal cancer, and this trial does not change the current standard of care. The finding differs from that of two other recent trials (PEAK and FIRE-3), which indicated a potential late survival benefit beyond 2 years of treatment, favoring EGFR-targeted agents over bevacizumab in the first line. However, CALGB 80405 is the only one of these trials to be adequately powered to determine a survival endpoint. Pending from this study is an evaluation of all RAS-mutant patients, which accounts for an additional 15%–17% of patients normally considered KRAS wild-type.
Hurwitz and colleagues presented promising results of a randomized, double-blind, placebo-controlled, phase II study of the JAK1/JAK2 inhibitor ruxolitinib plus capecitabine versus capecitabine alone as second-line chemotherapy in 127 patients with metastatic pancreatic cancer (abstract 4000). Patients received capecitabine (1000 mg/m2 twice daily for 14 days every 3 weeks) with or without ruxolitinib (15 mg twice daily).
Antitumor response was higher in the ruxolitinib arm than in the capecitabine-alone arm (7% vs. 0%). In a prespecified subgroup analysis of 60 patients with elevated C-reactive protein (a positive biomarker for inflammation), OS (the primary endpoint) was significantly improved with ruxolitinib (hazard ratio, 0.47; P=0.01), with 3- and 6-month OS rates of 48% and 42% versus 29% and 11%. Further study of this agent in subpopulations of metastatic pancreatic cancer patients using biomarkers of inflammation is likely.
Qin and colleagues reported results from China of a randomized, double-blind, placebo-controlled, phase III trial in which patients with metastatic gastric cancer were treated with apatinib, a VEGF receptor tyrosine kinase inhibitor (abstract 4003). A total of 270 patients received 850 mg daily of apatinib or placebo.
Median OS (the primary endpoint) was improved with apatinib versus placebo (195 vs. 140 days; hazard ratio, 0.71; P<0.016), as was PFS (78 vs. 53 days; HR, 0.44; P<0.0001). Limited response was seen with apatinib (2.8%) compared with no responses seen with placebo. Grade 3 or 4 adverse events were uncommon with apatinib and included hypertension, hand-foot syndrome, fatigue, and anorexia, each seen in <2% of patients.
Bruix and colleagues presented findings from a randomized, double-blind, placebo-controlled, phase III trial evaluating the multitargeted kinase inhibitor sorafenib in more than 1100 patients (62% Asian, 97% Child-Pugh A) with hepatocellular cancer undergoing resection (81%) or definitive local ablative therapy (abstract 4006). Patients received sorafenib (400 mg twice daily) or placebo for up to 4 years.
Recurrence-free survival (the primary endpoint) was identical with sorafenib or placebo (33.4 and 33.8 months, respectively), as was OS. The sorafenib group had a shorter median treatment duration (12.5 vs. 22.2 months) due to higher rates of treatment-related adverse events (24% vs. 7%) and consent withdrawal (17% vs. 6%). These negative results for adjuvant sorafenib for resected or ablated hepatocellular cancer are disappointing. Study of new agents in this disease is clearly warranted.