Efficacy of targeted therapies after PD1/PD-L1 inhibitors in metastatic clear cell renal cell carcinoma (mRCC): A multi-institution retrospective cohort.
Bibliographic record
Abstract
456 Background: Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors showed activity in mRCC and are currently in development in first-line and previously treated patients (pts). Whether these drugs will modify efficacy of subsequent targeted therapy (TT) including VEGFR tyrosine kinase inhibitors (TKI) or mTOR inhibitors is unknown. Methods: Medical records of RCC patients treated with investigational PD-1 or PD-L1 inhibitors who received subsequent treatment with TT were reviewed in 4 institutions. Baseline characteristics at the time of subsequent therapy and outcome data including time to treatment failure (TTF), best response, 1 and 2 year overall survival (OS) were retrospectively collected. Results: Of 89 pts who received PD-1/PD-L1 inhibitors, 56 patients (M/F 39/17, clear-cell 53, IMDC good 3/intermediate 16/poor 11/unknown 26) have received a subsequent therapy after PD-1/PD-L1 blockade, while 7 patients are still on therapy and 26 patients did not receive subsequent therapy. Among these 26 patients, 12 died from disease and 14 are still alive off-systemic therapies. 43 pts received VEGFR TKI and 13 received mTOR inhibitors as first subsequent TT. Median follow up from start of the subsequent TT is 16.1 months (range: 0.2, 30.6 months). TT post PD-1/PD-L1 was administered as second line in 9 patients (16%), third line in 24 patients (43%), > fourth line in 23 patients (41%). Median TTF was 6.9 months (range: 0.2+, 23.0), and was 6.9 and 5.7 months in patients who received VEGFR TKI and mTOR inhibitors respectively. One-year and 2-year OS from the initiation of subsequent TT was 58% (95% CI: 41-72%) and 36% (95% CI: 18%-54%), respectively. Investigator-assessed best response to subsequent TT was evaluated in 53 out of 56 patients: PR (n=7, 13%), SD (n=33, 62 %), and PD (n=13, 25%). Conclusions: This is the first report of TT efficacy after PD-1/PD-L1 inhibition. In this selected population, median TTF suggests a sustained benefit of both VEGFR TKI and mTOR inhibitors after PD-1/PDL1 inhibition.
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 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".