Summary Background The CLASSIC trial was done to compare adjuvant capecitabine plus oxaliplatin versus observation after D2 gastrectomy for patients with stage II or III gastric cancer. The planned ...interim analysis of CLASSIC (median follow-up 34 months) showed that adjuvant capecitabine plus oxaliplatin significantly improved disease-free survival, the primary endpoint, compared with observation after D2 gastrectomy. We report the 5-year follow-up data from the trial. Methods CLASSIC was a phase 3, randomised, open-label study done at 35 cancer centres, medical centres, and hospitals in China, South Korea, and Taiwan. Patients with stage II–IIIB gastric cancer who underwent curative D2 gastrectomy were randomly assigned (1:1) after surgery to receive adjuvant chemotherapy with capecitabine and oxaliplatin (eight 3-week cycles of oral capecitabine 1000 mg/m2 twice daily on days 1–14 plus intravenous oxaliplatin 130 mg/m2 on day 1) for 6 months or observation alone. Randomisation was stratified by country and disease stage with a permuted block (size four) design. Neither patients nor investigators were masked to treatment assignment. The primary outcome was 3-year disease-free survival in the intention-to-treat population. This analysis presents the final preplanned assessment of outcomes after 5 years. The study is registered with ClinicalTrials.gov , NCT00411229. Findings We enrolled 1035 patients: 520 were randomly assigned to adjuvant capecitabine and oxaliplatin, and 515 to observation. Median follow-up for this analysis in the intention-to-treat population was 62·4 months (IQR 54–70). 139 (27%) patients had disease-free survival events in the adjuvant capecitabine and oxaliplatin group versus 203 (39%) patients in the observation group (stratified hazard ratio HR 0·58, 95% CI 0·47–0·72; p<0·0001). Estimated 5-year disease-free survival was 68% (95% CI 63–73) in the adjuvant capecitabine and oxaliplatin group versus 53% (47–58) in the observation alone group. By the clinical cutoff date, 103 patients (20%) had died in the adjuvant capecitabine and oxaliplatin group versus 141 patients (27%) in the observation group (stratified HR 0·66, 95% CI 0·51–0·85; p=0·0015). Estimated 5-year overall survival was 78% (95% CI 74–82) in the adjuvant capecitabine and oxaliplatin group versus 69% (64–73) in the observation group. Adverse event data were not collected after the primary analysis. Interpretation Adjuvant treatment with capecitabine plus oxaliplatin after D2 gastrectomy should be considered for patients with operable stage II or III gastric cancer. Funding F Hoffmann La-Roche and Sanofi.
Abstract only
Introduction:
Statins reduce major cardiovascular events, but residual risk remains. The study examined determinants of atherosclerotic statin non-response in patients using statins.
...Hypothesis:
We hypothesized that a comprehensive evaluation of atherosclerosis identifies patients that progress atherosclerosis despite the use of statin therapy.
Methods:
The multi-center PARADIGM registry included patients who underwent serial CCTA ≥2 years apart, with whole-heart coronary tree quantification of vessel, lumen and plaque, and matching of baseline and follow-up coronary segments and lesions. Patients with statin use at baseline and follow-up CCTA were included. Atherosclerotic statin non-response was defined as an absolute increase in percent atheroma volume (PAV) of 1.0% or more per year. A secondary endpoint was defined by the additional requirement of progression of low-attenuation plaque or fibro-fatty plaque.
Results:
We included 649 patients (62.0±9.0 years, 63.5% male) on statin therapy and 205 (31.5%) experienced atherosclerotic statin non-response. Age, diabetes, hypertension, and all atherosclerotic plaque features (high risk plaque HRP features, calcified and noncalcified PAV, and lumen volume) were significantly different between patients with and without atherosclerotic statin non response, while only diabetes, the number of high risk plaque features, noncalcified and calcified PAV were independently associated with atherosclerotic statin non-response (OR:1.41 (0.95-2.11), OR:1.15 (1.09-1.21), OR:1.06 (1.02-1.10), OR:1.07 (1.03-1.12), respectively). For the secondary endpoint (N=125, 19.2%), only non-calcified PAV and number of HRP features were the independent determinants (OR:1.08 (1.03-1.13) and OR:1.21 (1.06-1.21), respectively).
Conclusions:
In patients treated with statins, baseline plaque characterization by plaque burden and high risk plaque is associated with atherosclerotic statin non-response defined as important progression of coronary atherosclerosis. Patients with the highest plaque burden including HRP were at highest risk for plaque progression, despite statin therapy. These patients may need additional therapies for further risk reduction.
