Abstract CT168: Randomized phase 2 trial of sunitinib or cediranib in alveolar soft part sarcoma
Notice bibliographique
Résumé
Abstract Background: Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor with few effective treatment options. Cediranib (C) and sunitinib (S) are potent oral inhibitors of all 3 VEGF receptors. Cediranib showed substantial single-agent activity (objective response rate [ORR] = 35%) in our previous trial in patients (pts) with metastatic ASPS (NCT00942877). Here we report a phase 2 randomized multicenter trial of single agent C or S in pts with ASPS (NCT01391962). Methods: We conducted a multicenter phase 2 trial with an optimal 2-stage design targeting an ORR of 40%. Enrolled pts were >16 years with metastatic ASPS, previously not treated (N) and unresectable, or previously treated (T), who have progressed per RECIST 1 within the 6-month period preceding enrollment. Pts were randomized to receive C (30 mg) or S (37.5 mg) orally, once a day, in 28-day cycles and could crossover to the other treatment arm at disease progression. ORR (primary endpoint), median progression-free survival (mPFS), and PFS rate at 24 weeks for the 2 arms (C and S) were evaluated; T and N cohorts were assessed separately in each arm. Arm accrual closed if ≤ 1 of the first 10 enrolled pts responded to the first treatment. Results: Thirty-four pts (47% white, 29.4% black, 17.6% Asian, 5.8% Pacific Islander) were enrolled; 29 pts were evaluable for response. One pt on each of the initial treatment arms had a confirmed partial response (PR), rates of 6.7% (1/154) and 7.1% (1/14) for C and S tx or tx-naive, respectively. Among pts who crossed over, there was 1 PR in a pt receiving C after initially responding (PR) on S (1/9; ORR 11.1%). Twenty-four pts had a best response of stable disease (86.7% and 78.6%) for C and S, respectively. The mPFS was 7.6 months (mo) (95% CI: 3.7-9.9 mo) and 5.5 mo (95% CI: 1.8-14.5 mo) for C and S, respectively administered as first therapy (p=0.92). PFS rate at 24 weeks was 62.5% (95% CI: 29.5-76.2%) and 50% (95% CI: 25.9-70.1%) for pts receiving C and S respectively, as initial therapy. There was no difference in mPFS between T or N pts in the C (6.7 mo [95% CI: 1.4-9.9 mo] vs 8.3 mo [95% CI: 2.7 - 16.6 mo]; P=0.35) arm, but some evidence of a potential difference in the S (4.8 mo [95% CI: 0.9-7.9 mo] vs 14.7 mo 95% CI: 1.8 - 21.6 mo]; P=0.058) arm. Overall, 43.7% (C) and 77.8% (S) of pts experienced grade ≥3 adverse events (AEs) at least possibly related to the study drug. Common grade ≥3 AEs included: diarrhea (C), neutropenia (S), hypertension (C and S). AEs were in line with the known safety profiles of each agent. As of August 2021, 1 pt (unevaluable for ORR) remains on study. Conclusions: The study did not meet its endpoints for ORR. There were no differences in mPFS for the 2 treatment arms. The selection of pts with more aggressive disease, who had progressed in the 6 months prior to enrollment, may account for the low patient response rates compared to our previous study of cediranib in ASPS. Funded by NCI Contract No. HHSN261200800001E. The study was a collaboration between NCI and Pfizer. Citation Format: Naoko Takebe, James Nguyen, Shivaani Kummar, Albiruni Abdul Razak, Sant P. Chawla, Suzanne George, Shreyaskumar R. Patel, Mary Louise Keohan, Sujana Movva, Geraldine O’Sullivan, Khanh Do, Larry Anderson, Lamin Juwara, Brooke Augustine, Seth Steinberg, Laura Kuhlmann, S. Percy Ivy, James H. Doroshow, Alice P. Chen. Randomized phase 2 trial of sunitinib or cediranib in alveolar soft part sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT168.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,003 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,013 | 0,002 |
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 source (Gemma direct ou Codex distillé), 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 ».