Gemcitabine and nab-paclitaxel combined with afatinib in metastatic pancreatic cancer - Results of a phase 1b clinical trial
Copyright © 2024. Published by Elsevier Ltd..
PURPOSE: The combination of gemcitabine/nab-paclitaxel is an established standard treatment in the first-line treatment of metastatic ductal adenocarcinoma of the pancreas (mPDAC). Afatinib, an oral second-generation pan ErbB family tyrosine kinase inhibitor, has shown promising pre-clinical signs in the treatment of pancreatic cancer. The aim of this phase 1b trial was to determine the maximum tolerated dose (MTD) of afatinib in combination with gemcitabine/nab-paclitaxel in patients with mPDAC.
METHODS: Treatment naïve patients (≥18 years) with histologically proven mPDAC and good performance status (ECOG 0/1) were enrolled to receive gemcitabine/nab-paclitaxel in combination with afatinib. Treatment was continued until disease progression, or unacceptable toxicity. The primary endpoint MTD was determined using a 3 + 3 design. Treatment started at dose level 0 with intravenous gemcitabine/nab-paclitaxel 1000 mg/m2 / 125 mg/m2 (day 1, 8, 15 of a 28-day cycle) + oral afatinib 30 mg daily. At dose level + 1 afatinib was increased to 40 mg. Secondary endpoints included safety parameters and exploratory endpoints evaluated treatment efficacy.
RESULTS: Twelve patients were included in this trial, and 11 patients were treated and analysed in the safety and full analysis set (FAS). At dose level 0 the first three patients did not experience a dose-limiting toxicity (DLT). At dose leve (DL) + 1 two patients experienced a DLT. Accordingly, enrolment continued at DL 0 with three more patients, of which one experienced DLT (skin rash ≥ CTCAE grade 3). Seven patients (63.6%) experienced at least one treatment-emergent serious adverse event (TESAE), with four patients (36.4%) experiencing TESAEs grade 3-5 related to the study medication. In the FAS, the objective response rate (ORR) was 36.4%, median progression-free survival (PFS) was 3.5 months and median overall survival in nine evaluable patients was 7.5 months.
CONCLUSIONS: In this phase 1b clinical trial, the MTD of gemcitabine/nab-paclitaxel (1000 mg/m2 / 125 mg/m2) and afatinib (30 mg) was established. In a cohort of 11 patients, the combination showed an acceptable safety profile.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:201 |
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| Enthalten in: |
European journal of cancer (Oxford, England : 1990) - 201(2024) vom: 15. März, Seite 113926 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Danmei [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.03.2024 Date Revised 15.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejca.2024.113926 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368914240 |
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| 245 | 1 | 0 | |a Gemcitabine and nab-paclitaxel combined with afatinib in metastatic pancreatic cancer - Results of a phase 1b clinical trial |
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| 500 | |a Date Revised 15.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024. Published by Elsevier Ltd. | ||
| 520 | |a PURPOSE: The combination of gemcitabine/nab-paclitaxel is an established standard treatment in the first-line treatment of metastatic ductal adenocarcinoma of the pancreas (mPDAC). Afatinib, an oral second-generation pan ErbB family tyrosine kinase inhibitor, has shown promising pre-clinical signs in the treatment of pancreatic cancer. The aim of this phase 1b trial was to determine the maximum tolerated dose (MTD) of afatinib in combination with gemcitabine/nab-paclitaxel in patients with mPDAC | ||
| 520 | |a METHODS: Treatment naïve patients (≥18 years) with histologically proven mPDAC and good performance status (ECOG 0/1) were enrolled to receive gemcitabine/nab-paclitaxel in combination with afatinib. Treatment was continued until disease progression, or unacceptable toxicity. The primary endpoint MTD was determined using a 3 + 3 design. Treatment started at dose level 0 with intravenous gemcitabine/nab-paclitaxel 1000 mg/m2 / 125 mg/m2 (day 1, 8, 15 of a 28-day cycle) + oral afatinib 30 mg daily. At dose level + 1 afatinib was increased to 40 mg. Secondary endpoints included safety parameters and exploratory endpoints evaluated treatment efficacy | ||
| 520 | |a RESULTS: Twelve patients were included in this trial, and 11 patients were treated and analysed in the safety and full analysis set (FAS). At dose level 0 the first three patients did not experience a dose-limiting toxicity (DLT). At dose leve (DL) + 1 two patients experienced a DLT. Accordingly, enrolment continued at DL 0 with three more patients, of which one experienced DLT (skin rash ≥ CTCAE grade 3). Seven patients (63.6%) experienced at least one treatment-emergent serious adverse event (TESAE), with four patients (36.4%) experiencing TESAEs grade 3-5 related to the study medication. In the FAS, the objective response rate (ORR) was 36.4%, median progression-free survival (PFS) was 3.5 months and median overall survival in nine evaluable patients was 7.5 months | ||
| 520 | |a CONCLUSIONS: In this phase 1b clinical trial, the MTD of gemcitabine/nab-paclitaxel (1000 mg/m2 / 125 mg/m2) and afatinib (30 mg) was established. In a cohort of 11 patients, the combination showed an acceptable safety profile | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Afatinib | |
| 650 | 4 | |a Pan-ErbB inhibitor | |
| 650 | 4 | |a Pancreatic cancer | |
| 650 | 4 | |a Phase 1 study | |
| 650 | 7 | |a Gemcitabine |2 NLM | |
| 650 | 7 | |a 130-nm albumin-bound paclitaxel |2 NLM | |
| 650 | 7 | |a Afatinib |2 NLM | |
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| 650 | 7 | |a Deoxycytidine |2 NLM | |
| 650 | 7 | |a 0W860991D6 |2 NLM | |
| 650 | 7 | |a Paclitaxel |2 NLM | |
| 650 | 7 | |a P88XT4IS4D |2 NLM | |
| 650 | 7 | |a Albumins |2 NLM | |
| 700 | 1 | |a Benedikt Westphalen, C |e verfasserin |4 aut | |
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| 700 | 1 | |a Waldschmidt, Dirk T |e verfasserin |4 aut | |
| 700 | 1 | |a Held, Swantje |e verfasserin |4 aut | |
| 700 | 1 | |a Kütting, Fabian |e verfasserin |4 aut | |
| 700 | 1 | |a Dorman, Klara |e verfasserin |4 aut | |
| 700 | 1 | |a Heinrich, Kathrin |e verfasserin |4 aut | |
| 700 | 1 | |a Weiss, Lena |e verfasserin |4 aut | |
| 700 | 1 | |a Boukovala, Myrto |e verfasserin |4 aut | |
| 700 | 1 | |a Haas, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Boeck, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Heinemann, Volker |e verfasserin |4 aut | |
| 700 | 1 | |a Probst, Victoria |e verfasserin |4 aut | |
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