Background
Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated.
Patients and methods
Patients were randomized (1 : 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m
2
orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m
2
intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m
2
orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m
2
intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal.
Results
Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10%) grade 3/4 treatment-related adverse events were neutropenia (14.3%) in the nivolumab plus SOX group, and neutropenia (16.7%), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1% each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1% (95% confidence interval 34.0–78.2) with nivolumab plus SOX and 76.5% (50.1–93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8–NR) and 10.6 months (5.6–12.5), respectively.
Conclusion
Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX.
Clinicaltrials.gov ID
NCT02746796.
Preventive EBD is an effective procedure to prevent postEMR/ESD stricture. Preventive EBD should be considered when EMR/ESD results in a mucosal defect with a circumference greater than three-fourths of the esophageal lumen.
BACKGROUND & AIMS: Esophagectomy is the standard treatment for stage I esophageal squamous cell carcinoma (ESCC). We conducted a single-arm prospective study to confirm the efficacy and safety of selective chemoradiotherapy (CRT) based on findings from endoscopic resection (ER). METHODS: We performed a prospective study of patients with T1b (SM1-2) N0M0 thoracic ESCC from December 2006 through July 2012; 176 patients underwent ER. Based on the findings from ER, patients received the following: no additional treatment for patients with pT1a tumors with a negative resection margin and no lymphovascular invasion (group A); prophylactic CRT with 41.4 Gy delivered to locoregional lymph nodes for patients with pT1b tumors with a negative resection margin or pT1a tumors with lymphovascular invasion (group B); or definitive CRT (50.4 Gy) with a 9-Gy boost to the primary site for patients with a positive vertical resection margin (group C). Chemotherapy comprised 5-fluorouracil and cisplatin. The primary end point was 3-year overall survival in group B, and the key secondary end point was 3-year overall survival for all patients. If lower limits of 90% confidence intervals for the primary and key secondary end points exceeded the 80% threshold, the efficacy of combined ER and selective CRT was confirmed. RESULTS: Based on the results from pathology analysis, 74, 87, and 15 patients were categorized into groups A, B, and C, respectively. The 3-year overall survival rates were 90.7% for group B (90% confidence interval, 84.0%-94.7%) and 92.6% in all patients (90% confidence interval, 88.5%-95.2%). CONCLUSIONS: In a prospective study of patients with T1b (SM1-2) N0M0 thoracic ESCC, we confirmed the efficacy of the combination of ER and selective CRT. Efficacy is comparable to that of surgery, and the combination of ER and selective CRT should be considered as a minimally invasive treatment option. UMIN-Clinical Trials Registry no.: UMIN000000553.
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