| Added by | celine.gongora |
|---|---|
| Group name | EquipeCG |
| Item Type | Journal Article |
| Title | Dual targeting of HER1/EGFR and HER2 with cetuximab and trastuzumab in patients with metastatic pancreatic cancer after gemcitabine failure: results of the "THERAPY"phase 1-2 trial |
| Creator | Assenat et al. |
| Author | Eric Assenat |
| Author | David Azria |
| Author | Caroline Mollevi |
| Author | Rosine Guimbaud |
| Author | Nicole Tubiana-Mathieu |
| Author | Denis Smith |
| Author | Jean-Pierre Delord |
| Author | Emmanuelle Samalin |
| Author | Fabienne Portales |
| Author | Christel Larbouret |
| Author | Bruno Robert |
| Author | Frédéric Bibeau |
| Author | Jean-Pierre Bleuse |
| Author | Evelyne Crapez |
| Author | Marc Ychou |
| Author | André Pèlegrin |
| Abstract | To improve treatment efficacy, we decided to simultaneously target HER1 and HER2 with trastuzumab and cetuximab. Following promising preclinical results, we conducted a phase 1-2 trial in advanced pancreatic cancer patients after first-line gemcitabine-based chemotherapy failure. In this single-arm, non-randomized, multicenter trial, patients received weekly cetuximab (400mg/m², then 250mg/m²). They were sequentially included in two trastuzumab dose levels: 3.0 or 4.0mg/kg, then 1.5 or 2.0mg/kg/weekly. Endpoints were the objective response rate, safety, progression-free (PFS) and overall survival (OS). During phase 1 (n=10 patients), toxicities were evenly distributed except for skin toxicities that frequently caused compliance issues. The higher dose level was defined as the trastuzumab recommended dose. During phase 2 (n=39 patients), toxicities were mainly cutaneous reactions and asthenia. No objective response was observed. Nine patients were stabilized but arrested treatment due to toxicity. Median PFS was 1.8 months (95%CI: 1.7-2.0 months) and median OS was 4.6 months (95%CI: 2.7-6.6 months). Both were positively correlated with skin toxicity severity (P=0.027 and P=0.001, respectively). Conventional phase 1 dose-escalation schedules are unsuitable for targeted therapies because most cutaneous toxicities are not considered dose-limiting toxicities. The compliance issues caused by skin toxicities were particularly detrimental because of the toxicity-response correlation. |
| Publication | Oncotarget |
| Volume | 6 |
| Issue | 14 |
| Pages | 12796-12808 |
| Date | May 20, 2015 |
| Journal Abbr | Oncotarget |
| Language | eng |
| DOI | 10.18632/oncotarget.3473 |
| ISSN | 1949-2553 |
| Short Title | Dual targeting of HER1/EGFR and HER2 with cetuximab and trastuzumab in patients with metastatic pancreatic cancer after gemcitabine failure |
| Library Catalog | PubMed |
| Extra | PMID: 25918250 PMCID: PMC4494975 |
| Tags | Adult, Aged, antibody combination, Antineoplastic Combined Chemotherapy Protocols, Cetuximab, Deoxycytidine, Disease-Free Survival, ErbB Receptors, Female, Humans, Kaplan-Meier Estimate, Male, Maximum Tolerated Dose, Middle Aged, original, Pancreatic Neoplasms, phase 1/2, Receptor, ErbB-2, Salvage Therapy, Trastuzumab |
| Date Added | 2019/05/14 - 12:01:37 |
| Date Modified | 2019/10/24 - 15:43:32 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
