Avelumab treatment in metastatic urothelial carcinoma: Post-hoc analysis of high-risk populations in the phase Ib JAVELIN Solid Tumor Study.
Bibliographic record
Abstract
428 Background: Avelumab is a human anti‒PD-L1 IgG1 antibody approved in the US, Canada, and Israel for the treatment of locally advanced or metastatic urothelial carcinoma (mUC) progressed after platinum chemotherapy. In the JAVELIN Solid Tumor study, patients (pts) in various subgroups had a favorable objective response rate (ORR) with avelumab. Here, we report further post hoc analyses of safety and efficacy outcomes with avelumab in high-risk mUC subgroups. Methods: Pts with mUC that had progressed after platinum-based therapy in the JAVELIN Solid Tumor study were analyzed. Best overall response (per RECIST 1.1) was adjudicated by an independent review committee. ORR, disease control rate (DCR), progression-free survival (PFS), and adverse event (AE) profiles for pre-specified subgroups of high-risk pts were compared. Results: 242 pts with mUC received avelumab and were followed up for ≥2 years (data cutoff, Apr 2018). No difference was found in ORR between pts with renal insufficiency (creatine clearance [CrCl], <60 mL/min; n=107) and pts with CrCl ≥60 mL/min (n=131; 17.8% [95% CI: 11.0-26.3] vs 15.3% [95% CI: 9.6-22.6]) or between pts with upper (n=56) vs lower tract tumors (n=186; 14.3% [95% CI: 6.4-26.2] vs 17.2% [95% CI: 12.1-23.4]). ORR in pts with baseline liver metastases (n=83) was 6.0% (95% CI: 2.0-13.5) vs 22.0% (95% CI: 15.8-29.3) in pts without (n=159). ORR in elderly pts (≥75 years; n=68) was 25.0% (95% CI: 15.3-37.0) vs 13.2% (95% CI: 8.6-19.2) in younger pts (n=174). ORR in pts with albumin ≥35 g/L (n=197) was 19.8% (95% CI: 14.5-26.1) vs 2.2% (95% CI: 0.1-11.8) in pts with <35 g/L (n=45). Except for the albumin levels and age subgroups (where the trend in ORR was not confirmed), subgroups showed DCR and PFS that were consistent with ORR trends. AE profiles did not exhibit any higher risk of adverse effects in these subgroups. Conclusions: Responses to avelumab occurred in select assessed subgroups previously defined as poor prognostic or high risk, suggesting that immunotherapy may achieve comparable efficacy irrespective of factors such as site of disease and renal status; no difference in safety profiles was identified. Clinical trial information: NCT01772004.
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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 | 0.006 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| 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".