| Added by | mollevi |
|---|---|
| Last modified by | André Pèlegrin |
| Group name | EquipeAP |
| 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 | E. Assenat |
| Author | D. Azria |
| Author | C. Mollevi |
| Author | R. Guimbaud |
| Author | N. Tubiana-Mathieu |
| Author | D. Smith |
| Author | J. P. Delord |
| Author | E. Samalin |
| Author | F. Portales |
| Author | C. Larbouret |
| Author | B. Robert |
| Author | F. Bibeau |
| Author | J. P. Bleuse |
| Author | E. Crapez |
| Author | M. Ychou |
| Author | A. Pelegrin |
| 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/m(2), then 250mg/m(2)). 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 |
| Pages | 12796-808 |
| Date | May 20 2015 |
| Journal Abbr | Oncotarget |
| ISSN | 1949-2553 (Electronic) 1949-2553 (Linking) |
| Tags | Equipe, original, top |
| Date Added | 2018/07/20 - 10:01:50 |
| Date Modified | 2019/12/19 - 08:46:51 |
| Notes and Attachments | (Note) (Note) (Note) (Note) 25918250 (Attachment) 25918250 (Attachment) |
Institut de Recherche en Cancérologie de
