Abstract CT131: A randomized (RCT) phase II study of oncolytic reovirus (pelareorep ) plus standard weekly paclitaxel (P) as therapy for metastatic breast cancer (mBC)
Notice bibliographique
Résumé
Abstract Background: Pelareorep is a Dearing strain of reovirus serotype 3, with demonstrated in vitro and in vivo activity in many cancers and synergistic cytotoxic activity with microtubule targeting agents, including taxanes. This study was designed to determine the efficacy and safety of pelareorep + P compared to P alone in mBC. Materials and Methods: This randomized, open-label, phase II study enrolled subjects who had mBC previously exposed to chemotherapy (CT). Subjects were randomized 1:1 between Arm A (P 80 mg/m2 day 1, 8 and 15 q 28 days plus pelareorep 3 x 1010 TCID50 day 1,2,8,9,15,16 q 28 days) and Arm B (P 80 mg/m2 day 1, 8 and 15 q 28 days). Treatment was continued until disease progression (PD) or unacceptable toxicity. Objective response was assessed every 8 weeks. Primary endpoint was progression free survival (PFS). The study had 90% power to detect an improvement of PFS from 4 to 7.5 months (HR 0.5, two-sided α=0.2). All p-values are two-sided. Results: Between July 2012 and April 2016, 81 subjects were accrued: 7 to the safety run-in for arm A, 36 to Arm A and 38 to Arm B. All had received prior CT, 59 as adjuvant treatment and 48 for mBC. Patients in Arm A had more favorable prognostic features, including lower LDH and less prior therapy. The median cumulative dose of P was 960 mg/m2 for arm A vs. 828 mg/m2 for arm B. Similar numbers of subjects in both arms required dose reductions, predominantly for myelosuppression. The median duration of treatment was 16.1 weeks for pelareorep and P in arm A and 14.1 weeks for P in arm B. With a median follow-up of 29.5 months, the median PFS was 3.78 mo for arm A and 3.38 mo for arm B (HR 1.04, 80% CI 0.76-1.43, p=0.87). Median OS was 17.4 mo for arm A and 10.4 mo for arm B (HR 0.65, 80% CI 0.46-0.91, p=0.1). Response rates (RR) were 25% for arm A and 23.7% for arm B (p=0.87). Pre-specified subset analysis found statistically significant differences in OS in patients with ECOG 1 or 2, aged < 65 yr, and no prior P treatment. Exploratory analysis of biomarkers found significant differences in OS in patients with wild type PIK3CA, KIT, APC, PTEN, ATM, AKT1, mutated TP53, and both wild type and mutated MET, although the number of pts was small. When grade 3 or higher adverse events (AE) were considered, only the incidence of fatigue was found in ≥10% (16% on Arm A vs 13%, arm B, p=0.76). Hematologic grade 3 or higher effects observed in ≥10% patients included lymphopenia (5% arm A vs 18% arm B, p=0.08), and neutropenia (23% arm A vs 26% arm B; p=0.8). There was a statistically significant difference in grade 3 or higher LDH (0% arm A vs 13% arm B, p=0.03). There were no treatment related deaths. Conclusions: This first, phase II, randomized study of pelareorep + P vs P in mBC previously exposed to CT, did not meet its primary endpoint of PFS. Despite similar PFS and RR there was a statistically significant improvement in OS for pelareorep + P pts. Given these data, further exploration of the role of pelareorep + P in mBC may be of interest. Citation Format: Vanessa Bernstein, Susan Ellard, Susan F. Dent, Karen A. Gelmon, Sukhbinder K. Dhesy-Thind, Mihaela Mates, Muhammed Salim, Lawrence Panasci, Xinni Song, Mark Clemons, Dongsheng Tu, Linda J. Hagerman, Lesley Seymour. A randomized (RCT) phase II study of oncolytic reovirus (pelareorep ) plus standard weekly paclitaxel (P) as therapy for metastatic breast cancer (mBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT131. doi:10.1158/1538-7445.AM2017-CT131
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 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 | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 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 ».