The mesenchymal transition subtype more responsive to dose dense taxane chemotherapy combined with carboplatin than to conventional taxane and carboplatin chemotherapy in high grade serous ovarian carcinoma: A survey of Japanese Gynecologic Oncology Group study (JGOG3016A1)

Ryusuke Murakami; Noriomi Matsumura; Hirofumi Michimae; Hiroshi Tanabe; Mayu Yunokawa; Haruko Iwase; Motoi Sasagawa; Toshiaki Nakamura; Osamu Tokuyama; Masashi Takano; Toru Sugiyama; Takashi Sawasaki; Seiji Isonishi; Kazuhiro Takehara; Hidekatsu Nakai; Aikou Okamoto; Masaki Mandai; Ikuo Konishi

doi:10.1016/j.ygyno.2019.02.010

The mesenchymal transition subtype more responsive to dose dense taxane chemotherapy combined with carboplatin than to conventional taxane and carboplatin chemotherapy in high grade serous ovarian carcinoma: A survey of Japanese Gynecologic Oncology Group study (JGOG3016A1)

Gynecol Oncol. 2019 May;153(2):312-319. doi: 10.1016/j.ygyno.2019.02.010. Epub 2019 Mar 8.

Authors

Ryusuke Murakami¹, Noriomi Matsumura², Hirofumi Michimae³, Hiroshi Tanabe⁴, Mayu Yunokawa⁵, Haruko Iwase⁶, Motoi Sasagawa⁷, Toshiaki Nakamura⁸, Osamu Tokuyama⁹, Masashi Takano¹⁰, Toru Sugiyama¹¹, Takashi Sawasaki¹², Seiji Isonishi⁴, Kazuhiro Takehara¹³, Hidekatsu Nakai¹⁴, Aikou Okamoto⁴, Masaki Mandai¹⁵, Ikuo Konishi¹⁶

Affiliations

¹ Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
² Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osaka, Japan. Electronic address: noriomi@kuhp.kyoto-u.ac.jp.
³ Kitasato University, School of Pharmacy, Department of Clinical Medicine (Biostatistics), Tokyo, Japan.
⁴ Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan.
⁵ Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁶ Department of Obstetrics and Gynecology, Kitasato University School of Medicine, Kanagawa, Japan.
⁷ Department of Gynecology, Niigata Cancer Center Hospital, Niigata, Japan.
⁸ Department of Obstetrics and Gynecology, Kagoshima City Hospital, Kagoshima, Japan.
⁹ Department of Gynecology, Osaka City General Hospital, Osaka, Japan.
¹⁰ Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Tokorozawa, Saitama, Japan.
¹¹ Department of Obstetrics and Gynecology, Iwate Medical University, Morioka, Iwate, Japan.
¹² Department of Obstetrics and Gynecology, National Hospital Organization, Kure Medical Center, Hiroshima, Japan.
¹³ Department of Gynecologic Oncology, National Hospital Organization Shikoku Cancer Center, Japan.
¹⁴ Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osaka, Japan.
¹⁵ Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osaka, Japan.
¹⁶ Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Obstetrics and Gynecology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.

PMID: 30853361
DOI: 10.1016/j.ygyno.2019.02.010

Abstract

Objective: Recently, we established new histopathological subtypes of high-grade serous ovarian cancer (HGSOC) that include the mesenchymal transition (MT) type, the immune reactive (IR) type, the solid and proliferative (SP) type and the papillo-glandular (PG) type. Furthermore, we identified that the mesenchymal transcriptome subtype might be sensitive to taxane. We investigated whether these different histopathological subtypes of HGSOC require individualized chemotherapy for optimal treatment.

Methods: We conducted the Japanese Gynecologic Oncology Group (JGOG) 3016A1 study, wherein we collected hematoxylin and eosin slides (total n = 201) and performed a histopathological analysis of patients with HGSOC registered in the JGOG3016 study, which compared the efficacy of conventional paclitaxel and carboplatin (TC) and dose-dense TC (ddTC). We analyzed the differences in progression-free survival (PFS) and overall survival (OS) among the four histopathological subtypes. We then compared the PFS between the TC group and the ddTC group for each histopathological subtype.

Results: There were significant differences in both PFS and OS among the four histopathological subtypes (p = 0.001 and p < 0.001, respectively). Overall, the MT subtype had the shortest PFS (median 1.4 y) and OS (median 3.6 y). In addition, the MT subtype had a longer PFS in the ddTC group (median 1.8 y) than in the TC group (median 1.2 y) (p = 0.01). Conversely, the other types had no significant difference in PFS when the two regimens were compared.

Conclusions: The MT type of HGSOC is sensitive to taxane; therefore, the ddTC regimen is recommended for this histopathological subtype.

Keywords: Dose dense TC; High grade serous ovarian carcinoma; Mesenchymal; Ovarian cancer; Taxane sensitivity.

Publication types

Comparative Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Cystadenocarcinoma, Serous / drug therapy*
Cystadenocarcinoma, Serous / mortality
Cystadenocarcinoma, Serous / pathology
Female
Gene Expression Profiling
Humans
Japan
Middle Aged
Oligonucleotide Array Sequence Analysis
Ovarian Neoplasms / drug therapy*
Ovarian Neoplasms / mortality
Ovarian Neoplasms / pathology
Ovary / pathology
Progression-Free Survival
Survival Analysis