Sequential use of sorafenib and sunitinib in advanced renal‐cell carcinoma (RCC): an Italian multicentre retrospective analysis of 189 patient cases
Notice bibliographique
Résumé
Study Type – Therapy (retrospective cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Various targeted agents with differing mechanisms of action and toxicity profiles have now been approved for the treatment of advanced RCC. However, the optimal use of these agents remains a challenge. Since the approval of sorafenib and sunitinib, many patients have been treated with these two tyrosine kinase inhibitors (TKIs) in sequence, with current evidence suggesting that this approach is associated with continued clinical benefit, with limited or no cross‐resistance between the two agents. The mammalian target of rapamycin (mTOR) inhibitor, everolimus, has been shown to be as effective after two TKIs as it is after one TKI, emphasizing the importance of understanding the optimal TKI sequence before switching to an mTOR inhibitor, to provide patients with the longest progression‐free survival (PFS) benefit. This retrospective analysis of 189 patients treated sequentially with sorafenib (800 mg/day) and sunitinib (50 mg/day; 4 weeks on 2 weeks off) showed that initial therapy with either agent was associated with similar PFS benefits (median PFS 8.4 months [sorafenib] vs 7.8 months [sunitinib]; HR 1.05, 95% CI 0.78–1.40; P = 0.758). However, patients treated with sorafenib followed by sunitinib (SoSu) appeared to derive a greater PFS benefit than those treated with SuSo (median PFS with second TKI: 7.9 months [SoSu] vs 4.2 months [SuSo]; HR 0.54, 95% CI 0.39–0.74; P < 0.001). Consistent with previous studies, these findings suggest that sequential TKI therapy is associated with continued clinical benefit and that SoSu may result in a longer PFS than SuSo. OBJECTIVE To conduct a retrospective, multicentre, cohort analysis to assess the sequential use of the tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib. PATIENTS AND METHODS Records of 189 patients with renal‐cell carcinoma (RCC) who were treated with sorafenib and sunitinib sequentially between March 2004 and April 2009 at 12 Italian study centres were analysed. Patients were treated under European Expanded Access Programmes or, following market approval, in general clinical practice. Interventions were sorafenib (800 mg/day) and sunitinib (50 mg every day; 4 weeks on and 2 weeks off). Progression‐free survival (PFS) during treatment with the first and second TKI was evaluated. RESULTS In all, 99 patients were treated with sunitinib followed by sorafenib (SuSo) and 90 were treated with sorafenib followed by sunitinib (SoSu); 104 (55%) patients had received prior systemic therapy, mostly with cytokines. The median (range) PFS on the first TKI was similar between treatment groups [sorafenib 8.4 (1.1–28.9) months; sunitinib 7.8 (0.5–30.4) months; hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.78–1.40, P = 0.758]. Multivariate analysis showed that good Memorial Sloan‐Kettering Cancer Center status was associated with increased PFS. After the second TKI, patients in the SoSu group had a longer median PFS than those in the SuSo group (7.9 months vs 4.2 months, respectively; HR 0.54, 95% CI 0.39–0.74, P < 0.001). Multivariate analysis showed only treatment and Eastern Cooperative Oncology Group performance status (and not age, gender, study centre or previous treatment) were significantly associated with duration of PFS. CONCLUSION Our findings suggest a limited cross‐resistance between sorafenib and sunitinib and that the sequence SoSu may result in a longer combined PFS than SuSo. This is the largest retrospective study to date, though its findings are limited in part by the retrospective nature.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».