METHODS: Data from the population-based Singapore Cancer Registry for 1968-1992 were used to determine time trends, inter-ethnic differences and the contributions of age, period and cohort effects to the incidence of the disease.
RESULTS: Our results revealed an average annual increase of 3.6% over the 25-year period for all women, form 20.2 per 100,000 women in the period 1968-1972 to 38.8 per 100,000 in 1988-1992. There was a statistically significant difference between the three major ethnic groups, the rate of increase being highest in Malays (4.4%) and lowest in Indians (1.4%). The overall increase was attributable to a strong cohort effect that remained significant when adjusted for time period for Chinese women and for all ethnic groups combined. The risk was observed to increase in successive birth cohorts from the 1890s to 1960s.
CONCLUSIONS: Our results suggest that breast cancer incidence rates are likely to continue to increase more sharply in the future as women born after the mid-20th century reach the high-risk age groups. They also suggest the pattern by which important aetiological factors for the disease in our population have exerted their effects, and provide support for the role of demographic and lifestyle changes as possible risk factors.
METHODS: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response.
RESULTS: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population.
CONCLUSIONS: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.