OBJECTIVE: To determine efficacy and safety of PDA10 in treating renal anaemia in haemodialysis patients, in comparison to the originator epoetin-α, Eprex®.
METHODS: A phase 3, multicentre, multi-national, double-blind, randomised, active-controlled and parallel group study conducted over 40 weeks in Malaysia and Korea. End stage kidney disease patients undergoing regular haemodialysis who were on erythropoietin treatment were recruited. The study has 3 phases, which included a 12-week titration phase, followed by 28-week double-blind treatment phase and 24-week open-label extension phase.
RESULTS: The PDA10 and Eprex® were shown to be therapeutically equivalent (p
CASE REPORT: In this case series, we report on two cases of WT which had poor response to pre-operative chemotherapy. Both cases underwent surgery after pre-operative chemotherapy and recovery was uneventful during a two-year follow-up.
DISCUSSION: Both patients had chemotherapy prior planned surgery, but had unfortunate poor tumour response. The tumour progressed in size which required a radical nephrectomy. The histology report for the first case had more than 60% blastemal cells remaining despite giving pre-operative chemotherapy with no focal anaplasia. This showed poor response to chemotherapy evidenced by the high number of blastemal cells. The second case was a stromal type WT which is known for poor response and may lead to enhancement of growth and maturation induced by chemotherapy. These were the possible reason of poor response of WT in these two cases.
METHODS: PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI).
RESULTS: Overall, 190 patients with a median age of 61 years (range: 22.0-96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving 10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%).
CONCLUSIONS: Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.
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.