Format

Send to

Choose Destination
Gastric Cancer. 2019 Apr 3. doi: 10.1007/s10120-019-00958-4. [Epub ahead of print]

A phase I/II study of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer.

Author information

1
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
2
Chungbuk National University College of Medicine, Cheongju, South Korea.
3
Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
4
Hallym University Sacred Heart Hospital, Anyang-si, South Korea.
5
Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
6
National Cancer Center, Seoul, South Korea.
7
Seoul National University Boramae Medical Center, Seoul, South Korea.
8
Sungkyunkwan University Samsung Medical Center, Seoul, South Korea.
9
Chonbuk National University Medical School, Jeonju, South Korea.
10
Hanmi Pharmaceutical Co., Ltd., Seoul, South Korea.
11
Korea University Anam Hospital, Seoul, South Korea.
12
Gangnam Severance Hospital, Seoul, South Korea.
13
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea. bangyj@snu.ac.kr.

Abstract

BACKGROUND:

Poziotinib (HM781-36B) is an irreversible pan-HER tyrosine kinase inhibitor which targets EGFR, HER2, and HER4. This prospective, multicenter, open-label, phase I/II study determined the maximum tolerated dose (MTD) and evaluated the safety and efficacy of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer (GC).

METHODS:

Patients with HER2-positive GC previously treated with one line of chemotherapy received oral poziotinib (8 mg or 12 mg) once daily for 14 days, followed by 7 days off. Paclitaxel (175 mg/m2 infusion) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg infusion) were administered concomitantly with poziotinib on day 1 every 3 weeks.

RESULTS:

In the phase I part, 12 patients were enrolled (7 at dose level 1, 5 at dose level 2). One patient receiving poziotinib 8 mg and 2 receiving poziotinib 12 mg had dose-limiting toxicities (DLTs); all DLTs were grade 4 neutropenia, one with fever. The most common poziotinib-related adverse events were diarrhea, rash, stomatitis, pruritus and loss of appetite. The MTD of poziotinib was determined to be 8 mg/day and this was used in the phase II part which enrolled 32 patients. Two patients (6.3%) had complete responses and 5 (15.6%) had partial responses (objective response rate 21.9%). Median progression-free survival and overall survival were 13.0 weeks (95% CI 9.8-21.9) and 29.5 weeks (95% CI 17.9-59.2), respectively.

CONCLUSIONS:

The MTD of poziotinib combined with paclitaxel and trastuzumab was 8 mg/day. This combination yielded promising anti-tumor efficacy with manageable toxicity in previously treated patients with HER2-positive GC.

KEYWORDS:

Chemotherapy; Gastric cancer; HER2; Poziotinib; Trastuzumab

PMID:
30945121
DOI:
10.1007/s10120-019-00958-4

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center