Safety and efficacy of sorafenib in elderly patients (pts) ≥65 years: A subset analysis from the Advanced Renal Cell Carcinoma Sorafenib (ARCCS) Expanded Access Program in North America
Bibliographic record
Abstract
5045 Background: Sorafenib, an orally active multikinase inhibitor, has been approved by the US Food and Drug Administration for the treatment of advanced RCC. Prior to the drug’s approval for RCC, the North American ARCCS expanded access program was initiated to make sorafenib available to patients (pts) who were not eligible for or did not have access to sorafenib clinical trials in the United States and Canada. Because sorafenib is likely to be used in elderly pts with advanced RCC, we evaluated its safety and efficacy profile in a subset of pts ≥65 years (yrs) who enrolled in the ARCCS program. Methods: Eligible pts were ≥15 yrs of age with advanced RCC, Eastern Cooperative Oncology Group performance status of 0–2 (with waivers granted for pts with status 3–4), and adequate prior therapy of brain metastases. Major exclusion criteria included treatment with other investigational drugs in the 4 weeks prior to enrollment; life expectancy <2 months; active coronary artery disease, ischemia or hypertension; and renal impairment requiring dialysis. Pts received oral sorafenib 400 mg bid as a single agent until disease progression or intolerance. Results: Of 2,504 pts assessed for safety, 1,135 (45%) pts were ≥65 yrs. Grade 2 and Grade ≥3 adverse events (AEs) observed in ≥5% of pts ≥65 yrs and <65 yrs are listed in the table. Grade ≥3 cardiac-related AEs were reported in 8% of pts ≥65 yrs and in 7% of pts <65 yrs. Of the 762 pts >65 yrs of age who were evaluable for response, partial response was reported in 3% and stable disease in 81%. Conclusions: In the ARCCS program, sorafenib 400 mg bid was associated with similar rates of clinically manageable side effects in elderly pts with advanced RCC as compared to younger pts. Response rates to sorafenib in elderly pts were comparable to previously reported results for total ARCCS pts and phase III data for sorafenib 400 mg bid in advanced RCC.Grade 2 and ≥ 3 AEs observed in ≥ 5% of pts ≥ 65 yrs (n = 1,135) and < 65 yrs (n = 1,361) Adverse Events Grade 2 (%) Grade 2 (%) Grade ≥3 (%) Grade ≥3 (%) ≥65 yrs <65 yrs ≥65 yrs <65 yrs Hand-foot skin reaction 7 10 9 10 Rash/desquamation 10 8 6 4 Fatigue 8 7 8 4 Hypertension 8 8 5 5 Diarrhea 6 6 3 3 Nausea 3 5 2 3 Anorexia 6 4 2 2 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer HealthCare Bayer/Onyx, Pfizer, Wyeth, Genentech, Novartis, Antigenics, Bayer/Onyx, Pfizer, Genentech, Wyeth, Novartis Bayer/Onyx, Pfizer, Genentech, Wyeth
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".