PATIENTS AND METHODS: Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.
RESULTS: A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.
CONCLUSION: These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).
MATERIALS AND METHODS: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours.
RESULTS: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor.
CONCLUSION: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.
PATIENTS AND METHODS: For this individual patient data meta-analysis, sociodemographic and smoking behavior information of 12 414 incident CRC patients (median age at diagnosis: 64.3 years), recruited within 14 prospective cohort studies among previously cancer-free adults, was collected at baseline and harmonized across studies. Vital status and causes of death were collected for a mean follow-up time of 5.1 years following cancer diagnosis. Associations of smoking behavior with overall and CRC-specific survival were evaluated using Cox regression and standard meta-analysis methodology.
RESULTS: A total of 5229 participants died, 3194 from CRC. Cox regression revealed significant associations between former [hazard ratio (HR) = 1.12; 95 % confidence interval (CI) = 1.04-1.20] and current smoking (HR = 1.29; 95% CI = 1.04-1.60) and poorer overall survival compared with never smoking. Compared with current smoking, smoking cessation was associated with improved overall (HR<10 years = 0.78; 95% CI = 0.69-0.88; HR≥10 years = 0.78; 95% CI = 0.63-0.97) and CRC-specific survival (HR≥10 years = 0.76; 95% CI = 0.67-0.85).
CONCLUSION: In this large meta-analysis including primary data of incident CRC patients from 14 prospective cohort studies on the association between smoking and CRC prognosis, former and current smoking were associated with poorer CRC prognosis compared with never smoking. Smoking cessation was associated with improved survival when compared with current smokers. Future studies should further quantify the benefits of nonsmoking, both for cancer prevention and for improving survival among CRC patients, in particular also in terms of treatment response.