Adjuvant axitinib in Asian vs non-Asian patients with metastatic renal cell carcinoma (mRCC): ATLAS trial subgroup analysis

Abstract

Abstract Background The ATLAS trial compared axitinib (AXI) vs placebo in patients (pts) with locoregional renal cell carcinoma at risk of recurrence after nephrectomy. ATLAS was stopped due to futility at a pre-planned interim analysis. A subgroup analysis was performed to describe differences between Asian vs Non-Asian pts and different Asian groups by geography in baseline characteristics and safety. Methods The exploratory subgroup analysis population included 363 pts randomized to receive AXI and 361 randomized to placebo. The primary endpoint was disease-free survival (DFS). Results DFS had the largest treatment effect in highest risk pts for Asian and Non-Asian pts: Hazard ratio = 0.731 (Asians) vs. 0.755 (Non-Asians). A similar trend was noted for Fuhrman Grade 3-4. Additional key results from the analysis are presented in the table. Table . 211P Summary of key findings Axitinib N\u2009=\u2009363 Placebo N\u2009=\u2009361 Asian N\u2009=\u2009262 Non- Asian N\u2009=\u2009101 Asian N\u2009=\u2009264 Non- Asian N\u2009=\u200997 Key Pts Characteristics Pts in Highest Risk Group, % 51.9 72.3 51.5 66.0 Median time since diagnosis, wk 8.7 10.3 8.6 10.0 Drug Treatment Differences Completed 3y Treatment, % 31.5 15.0 31.1 15.6 Median Treatment Duration, mo 25.3 15.6 27.0 22.9 Median Daily Dose, mg 6.6 8.6 9.9 10.0 Pts Safety Experience Frequency of Dose Reduction, % 68.5 50.0 11.7 7.3 AE Leading to Dose Reduction, % 58.8 46.0 7.6 10.4 AE Leading to Discontinuation, % 27.3 15.0 12.1 10.4 AE=adverse events Asian pts on AXI had higher frequencies of proteinuria, hypothyroidism, and nasopharyngitis and lower frequencies of fatigue and asthenia compared to Non-Asian pts on AXI. Within major Asian groups, proteinuria, hypothyroidism, nasopharyngitis and hypertension were more common in Japanese > Korean > Chinese pts. Conclusions DFS did not vary based on ethnicity. Asian pts had a lower median daily dose, and more frequent dose reduction vs non-Asian pts. More Asian pts had AEs leading to dose reductions of AXI and study withdrawals vs non-Asian pts. There were notable differences in AEs between Asian and Non-Asian pts and between Japanese, Korean and Chinese pts. Clinical trial identification NCT01599754. Editorial acknowledgement The study is sponsored by Pfizer. Medical writing support was provided by Charles Cheng, MS, of Engage Scientific Solutions, and funded by Pfizer. Legal entity responsible for the study This study was sponsored by Pfizer Inc and SFJ Pharmaceuticals. Funding This study was sponsored by Pfizer Inc and SFJ Pharmaceuticals. Disclosure C.F. Ng: Advisory / Consultancy, Speaker Bureau / Expert testimony: Boston Scientific; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ferring; Speaker Bureau / Expert testimony: Amgen; Research grant / Funding (institution): Olympus. T.G. Kwon: Research grant / Funding (institution): Kyungpook National University Chilgok Hospital. M. Eto: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): ONO; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Bayer. S.I. Seo: Honoraria (self): Ipsen; Honoraria (self): Pfizer; Research grant / Funding (self): Alvogen. B. Rosbrook: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. E. Grande: Honoraria (self), Research grant / Funding (self): Pfizer; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (self): IPSEN; Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self): Eisai; Honoraria (self): Eusa Pharma; Honoraria (self): MSD; Honoraria (self): Sanofi-Genzyme; Honoraria (self): Adacap; Honoraria (self): Novartis; Honoraria (self): Pierre Fabre; Honoraria (self), Research grant / Funding (self): Lexicon; Honoraria (self): Celgene; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): MTEM/Threshold. M. Gross-Goupil: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (self): Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Amgen. D.I. Quinn: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Bayer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Genentech; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Astellas. All other authors have declared no conflicts of interest.