Long-term safety of avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC) in the JAVELIN Bladder 100 trial.
Bibliographic record
Abstract
4516 Background: In the phase 3 JAVELIN Bladder 100 trial (NCT02603432), patients (pts) with aUC without progression after 1L platinum-based chemotherapy had significantly prolonged overall survival and progression-free survival with avelumab 1L maintenance + best supportive care (BSC) vs BSC alone. The safety profile of avelumab 1L maintenance was consistent with prior avelumab monotherapy studies, with no new safety signals identified and no detrimental impact on quality of life. Results led to the adoption of avelumab 1L maintenance into international guidelines as standard of care. We report post hoc safety analyses after a minimum 2 years of follow-up. Methods: Eligible pts had unresectable locally advanced or metastatic UC without progression after 1L platinum-based chemotherapy. Here, pts who received treatment in the avelumab + BSC arm were analyzed. Trial treatment continued until confirmed progression, unacceptable toxicity, or withdrawal of consent. Results: At data cutoff (June 4, 2021), median follow-up in the avelumab arm was 38.0 months. In 344 pts who received ≥1 dose of avelumab, median treatment duration was 5.8 months (range, 0.5-49.7) and median number of infusions was 11.5 (range, 1.0-106.0). Treatment-related adverse events (TRAEs) of any grade occurred in 269 pts (78.2%). Grade ≥3 TRAEs occurred in 67 pts (19.5%); the most common (>2%) were lipase increased (n=12; 3.5%) and amylase increased (n=8; 2.3%). 40 pts (11.6%) had a TRAE that led to avelumab discontinuation. Immune-related AEs (irAEs) occurred at any grade in 111 pts (32.3%) and at grade ≥3 in 26 (7.6%). The most common categories of irAEs (any grade in >5%) were thyroid disorders (n=44; 12.8%) and immune-related rash (n=37; 10.8%); the most common categories of grade ≥3 irAEs (>1%) were immune-related rash and hepatitis (each n=5; 1.5%). Serious irAEs occurred in 18 pts (5.2%), of which immune-related nephritis/renal dysfunction (n=4; 1.2%) was the most common category. 21 pts (6.1%) had an irAE that led to avelumab discontinuation; the most common categories (>1%) were immune-related hepatitis and nephritis/renal dysfunction (each n=4; 1.2%). Among 118 pts treated with avelumab for ≥12 months, irAEs occurred after 12 months in 27 pts (22.9%), including grade ≥3 irAEs in 5 (4.2%). The most common category of irAEs occurring after 12 months (any grade in >5%) was immune-related rash (n=12; 10.2%). No category of grade ≥3 irAEs occurred after 12 months in >1 pt. Conclusions: Post hoc analyses from JAVELIN Bladder 100 confirm the acceptable long-term safety profile of avelumab 1L maintenance. Grade ≥3 TRAEs or irAEs occurred in relatively low proportions of pts, and no new safety signals were identified with longer treatment. These results further support the use of avelumab 1L maintenance until progression as standard of care for pts with aUC without progression after 1L platinum-based chemotherapy. Clinical trial information: NCT02603432 .
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".