Abstract P4-07-02: Toxicity profile of single agent trastuzumab deruxtecan in solid tumors: A meta-analysis
Notice bibliographique
Résumé
Abstract Background: Trastuzumab deruxtecan (T-DXd) has been evaluated in numerous solid tumors and has been approved for metastatic HER2-positive breast and gastric/gastroesophageal cancers. We aimed to provide a precise estimate of toxicity of T-DXd observed in clinical trials. Methods: A systematic literature search was performed in PubMed and supplemented by review of abstracts from ASCO and ESMO. Eligible studies were clinical trials (dose-expansion phase 1, phase 2, and phase 3) investigating single agent T-DXd. The search was performed in June 2022. For single-arm trials, meta-analysis comprised one-sample proportions to obtain the random effects estimates of toxicity and respective 95% confidence intervals (CI) for T-DXd, while for randomized trials, the Mantel-Haenszel odds ratio method was utilized. Results: Fifteen trials comprising 1566 participants were evaluable for toxicity. ECOG Performance Status (PS) was reported in 11 studies and was ≥ 2 in only a single patient. The median age at enrollment was reported for 13 studies and was 57.5 years. Seven trials comprising 1023 (65.3%) participants evaluated T-DXd for breast cancer. From available data, 1209/1440 (84%)of participants were female and 735/1551 (47%) were from East Asia. The median follow-up time was 11.1 months (13 studies) and median previous lines of treatment were 3 (12 studies). All-grade toxicity rate of ≥10% was reported for most toxicities; however, grade ≥3 toxicity rate of ≥10% was reported only for neutropenia and anemia; 17.4% (95%CI 12-22.8) and 14.8% (95%CI 8.6-21), respectively (Table 1). Interstitial lung disease/pneumonitis (ILD) was reported in 203 (12.4%) patients, including 160 (9.41%) grade 1-2, and 23 (1.1%) grade 3-4. Treatment-related death was reported in 20 (1%) patients, and all were due to grade 5 ILD. No significant difference in ILD was identified in subgroup analysis of trials conducted in east Asia vs. the rest of the world, breast vs. other solid tumors, 5.4mg/kg vs. other doses, median follow-up < 12 months vs. ≥12 months or median previous lines ≥3 vs. < 3. In the three randomized clinical trials, grade ≥3 toxicity was significantly higher for nausea (OR: 9.32, 95%CI: 2.53-34.32), ILD (OR: 5.35, 95%CI: 0.97, 29.48), fatigue (OR:2.5, 95%CI: 1.11-5.66), and anemia (OR:1.77 95%CI: 1.14-2.74). Conclusions: T-DXd was associated with infrequent grade ≥3 toxicities across clinical trials. Grade 1-2 ILD was more common; however, grade 3-4 ILD occurred in 1.1%. This may be related to active monitoring of this toxicity in clinical trials and discontinuation of treatment in participants with G2 ILD. There is lack of evidence for the safety of T-DXd in patients with ECOG PS ≥ 2. Citation Format: Faris Tamimi, Abhenil Mittal, Consolacion Molto Valiente, Massimo Di Iorio, Laith Al-Showbaki, Michelle Nadler, Eitan Amir. Toxicity profile of single agent trastuzumab deruxtecan in solid tumors: A meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-02.
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 | 0,022 | 0,032 |
| Méta-épidémiologie (sens strict) | 0,003 | 0,001 |
| Méta-épidémiologie (sens large) | 0,016 | 0,078 |
| Bibliométrie | 0,005 | 0,006 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,004 | 0,002 |
| Science ouverte | 0,002 | 0,002 |
| Intégrité de la recherche | 0,002 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,001 |
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 ».