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

Tae Yong Kim, Hye Sook Han, Keun Wook Lee, Dae Young Zang, Sun Young Rha, Young Iee Park, Jin Soo Kim, Kyung Hun Lee, Se Hoon Park, Eun Kee Song, Soo A. Jung, Na Mi Lee, Yeul Hong Kim, Jae Yong Cho, Yung Jue Bang

Research output: Contribution to journalArticle

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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/m 2 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.

Original languageEnglish
JournalGastric Cancer
DOIs
Publication statusPublished - 2019 Jan 1

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Paclitaxel
Stomach Neoplasms
Maximum Tolerated Dose
Trastuzumab
HM781-36B
Stomatitis
Appetite
Pruritus
Exanthema
Neutropenia
Protein-Tyrosine Kinases
Disease-Free Survival
Diarrhea
Fever
Safety
Drug Therapy
Survival

Keywords

  • Chemotherapy
  • Gastric cancer
  • HER2
  • Poziotinib
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research

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A phase I/II study of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer. / Kim, Tae Yong; Han, Hye Sook; Lee, Keun Wook; Zang, Dae Young; Rha, Sun Young; Park, Young Iee; Kim, Jin Soo; Lee, Kyung Hun; Park, Se Hoon; Song, Eun Kee; Jung, Soo A.; Lee, Na Mi; Kim, Yeul Hong; Cho, Jae Yong; Bang, Yung Jue.

In: Gastric Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Kim, TY, Han, HS, Lee, KW, Zang, DY, Rha, SY, Park, YI, Kim, JS, Lee, KH, Park, SH, Song, EK, Jung, SA, Lee, NM, Kim, YH, Cho, JY & Bang, YJ 2019, 'A phase I/II study of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer', Gastric Cancer. https://doi.org/10.1007/s10120-019-00958-4
Kim, Tae Yong ; Han, Hye Sook ; Lee, Keun Wook ; Zang, Dae Young ; Rha, Sun Young ; Park, Young Iee ; Kim, Jin Soo ; Lee, Kyung Hun ; Park, Se Hoon ; Song, Eun Kee ; Jung, Soo A. ; Lee, Na Mi ; Kim, Yeul Hong ; Cho, Jae Yong ; Bang, Yung Jue. / A phase I/II study of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer. In: Gastric Cancer. 2019.
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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/m 2 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.",
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T1 - A phase I/II study of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer

AU - Kim, Tae Yong

AU - Han, Hye Sook

AU - Lee, Keun Wook

AU - Zang, Dae Young

AU - Rha, Sun Young

AU - Park, Young Iee

AU - Kim, Jin Soo

AU - Lee, Kyung Hun

AU - Park, Se Hoon

AU - Song, Eun Kee

AU - Jung, Soo A.

AU - Lee, Na Mi

AU - Kim, Yeul Hong

AU - Cho, Jae Yong

AU - Bang, Yung Jue

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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/m 2 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.

AB - 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/m 2 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.

KW - Chemotherapy

KW - Gastric cancer

KW - HER2

KW - Poziotinib

KW - Trastuzumab

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