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Grade 3 non infectious pneumonitis was reported in 4 patients, all of whom had lung metastases at study entry 3 events improved to grade 1 2 after steroid therapy, oxygen inhalation, and or dose adjustment. 1 event of pulmonary fibrosis improved to grade 2 following Abstain From
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Ascomycin Totally discontinuation of everolimus. Overall, no grade 4 non infectious pneumonitis was reported. The probability of onset of non infectious pneumonitis was estimated to be 6% at 1 month and 32% at 4 months. The median time to first occurrence of non infectious pneumonitis was not reached. The most frequently observed laboratory abnormalities were decreased hemoglobin, increased triglycer ides, increased fasting glucose, increased cholesterol, and decreased absolute lymphocyte count.
Common grade 3 4 laboratory abnormal ities included decreased hemoglobin, decreased absolute lymphocytes, and increased GGT. Efficacy At the data cut off date, median PFS was estimated to be 6. 9 months. The estimated probability of PFS was 62% at 4 months, 52% at 6 months, and 36% at 12 months. Median OS was not reached. The estimated probability of OS was 76% at 6 months and 56% at 12 months. Confirmed objective tumor responses evaluated by investigator assessment were seen in 3 patients, corre sponding to an ORR of 5%. Stable disease was reported in 39 patients. Everolimus ther apy in this patient population was associated with a DCR of 66%. Pharmacokinetics Mean Cmin after administration of everolimus 10 mg day was 21. 4 12. 4 ng mL at cycle 2, day 1 and 15. 0 9. 97 ng mL at cycle 4, day 1. Mean Cmin after ad ministration of everolimus 5 mg day was 0.
7 ng mL at cycle 2, day 1 and 8. 8 1. 14 ng mL at cycle 4, day 1. Mean Cmin at cycle 4, day 1 at the 10 mg day dose was approximately twice the mean Cmin value at the 5 mg day dose, which confirms a dose proportional increase in pre dose exposure of everolimus after daily administration. In the analysis of PFS, the estimated risk ratio of 0. 67 suggested a trend toward longer PFS with higher time normalized everolimus Cmin. However, the corresponding 95% CI included unity, thereby precluding conclusion of any statistically significant relationship. There was no apparent difference between patients in the evero limus time normalized Cmin categories of 10 ng mL, 10 25 ng mL, and 25 ng mL and all grades of non infectious pneumonitis and stomatitis oral mucositis. Discussion This phase 1b study was planned and conducted to evaluate the safety and efficacy profile of everolimus in Chinese patients with mRCC after failure of VEGFr TKI therapy. Overall safety findings from this study were consistent with those reported in the phase 3 RECORD 1 study and with a phase 1 study conducted in Chinese patients with advanced solid tumors.