Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma: 5-year analysis of KEYNOTE-426.
Bibliographic record
Abstract
LBA4501 Background: At the first interim analysis of the randomized, open-label, phase 3 KEYNOTE-426 (NCT02853331) study, 1L pembro + axi showed statistically significant OS, PFS, and ORR over sun for advanced ccRCC. We report results with 5-y minimum follow-up. Methods: Adults with confirmed locally advanced or metastatic ccRCC with or without sarcomatoid features, no previous systemic therapy for metastatic ccRCC, KPS ≥70%, and ≥1 lesion measurable per RECIST v1.1 were randomly assigned 1:1 to receive pembro 200 mg IV Q3W for 35 doses (~2 y) + axi 5 mg PO BID or sun 50 mg PO QD on a 4-wk-on/2-wk-off schedule. Dual primary end points were OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary end points included ORR and DOR per RECIST v1.1 by BICR, and safety. A post hoc analysis adjusting for the effect of subsequent therapy on OS using a 2-stage adjustment model was conducted. Results: Of 861 enrolled patients (pts), 432 were assigned to pembro + axi and 429 to sun. Median study follow-up was 67.2 mo (range, 60.0-75.0). Efficacy for the ITT population and IMDC risk subgroups are shown in table. For pembro + axi vs sun, the 60-mo OS rates were 41.9% vs 37.1%, and the 60-mo PFS rates were 18.3% vs 7.3%. Median DOR (range) was 23.6 mo (1.4+ to 68.6+) for pembro + axi and 15.3 mo (2.3-68.3) for sun. In pts who discontinued treatment, 237/381 pts (62.2%) in the pembro + axi arm and 300/406 pts (73.9%) in the sun arm received subsequent anticancer treatment. The HR for OS when adjusted for subsequent therapy was 0.67 (95% CI, 0.52-0.84). Clinical data on pts who completed 2 y of pembro will be presented. No new safety signals were observed. Conclusions: After 5 y of follow-up, pembro + axi had sustained OS, PFS, and ORR benefits over sun in advanced ccRCC. These results are the longest follow-up to date of an anti–PD-1/L1 inhibitor + VEGFR TKI in this pt population and continue to support the use of pembro + axi as a 1L standard of care for advanced ccRCC. Clinical trial information: NCT02853331 .
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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 | 0.009 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.006 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".