Outcomes of Patients with Metastatic Renal Cell Carcinoma Treated with Targeted Therapy After Immuno-oncology Checkpoint Inhibitors
Why this work is in the frame
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Bibliographic record
Abstract
BACKGROUND: Immuno-oncology (IO) therapies have changed the treatment standards of metastatic renal cell carcinoma (mRCC). However, the effectiveness of targeted therapy following discontinuation of IO therapy in real-world settings has not been well studied. OBJECTIVE: To describe treatment sequence and assess clinical effectiveness of targeted therapy for mRCC patients who received prior IO therapy. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, longitudinal cohort study using data from eight international cancer centers was conducted. Patients with mRCC were ≥18yr old, received IO therapy in any line, and initiated targeted therapy following IO therapy discontinuation. INTERVENTION: Patients were treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) or mammalian target of rapamycin inhibitors (mTORIs). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were time to treatment discontinuation (TTD), overall survival (OS), and objective response rate (ORR). Crude and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. Models were adjusted for age, sex, therapy line, and International Metastatic RCC Database Consortium risk group. RESULTS AND LIMITATIONS: Among 314 patients, 276 (87.9%) and 38 (12.1%) were treated with VEGFR-TKI and mTORI therapy, respectively. The most common tyrosine kinase inhibitor treatments were axitinib, cabozantinib, and sunitinib following IO therapy. In adjusted models, patients treated with VEGFR-TKI versus mTORI therapy had lower hazard of TTD after IO treatment (aHR=0.46; 95% CI: 0.30-0.71; p < 0.01). One-year OS probability (65% vs 47%, p < 0.01) and proportion of ORR (29.8% vs 3.6%, p < 0.01) were significantly greater for patients treated with VEGFR-TKIs versus those treated with mTORIs. CONCLUSIONS: Targeted therapy has clinical activity following IO treatment. Patients who received VEGFR-TKIs versus mTORIs following IO therapy had improved clinical outcomes. These findings may help inform treatment guidelines and clinical practice for patients post-IO therapy. PATIENT SUMMARY: Patients may continue to experience clinical benefits from targeted therapies after progression on immuno-oncology treatment.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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 it