Is the mesenchymal transition subtype more responsive to dose dense taxane chemotherapy combined with carboplatin (ddTC) than to conventional taxane and carboplatin chemotherapy (TC) in high grade serous ovarian carcinoma? A survey of Japanese Gynecology Oncology Group study (JGOG3016A1).

Abstract

5510 Background: High-grade serous ovarian cancer (HSOC) was divided into four transcriptome subtypes (i.e. Mesenchymal, Immunoreactive, Proliferative, and Differentiated). We established a new pathological classification based on these transcriptome subtypes: Mesenchymal Transition (MT) type, Immune Reactive (IR) type, Solid and Proliferative (SP) type and Papillo-Glandular (PG) type (PMID: 26993207). The MT type has the worst prognosis. We discovered the Mesenchymal transcriptome subtype might be sensitive to taxane chemotherapy. Therefore, we hypothesized that the MT type, which represents the Mesenchymal transcriptome subtype, may respond better to dose dense taxane combined with carboplatin (ddTC) rather than to conventional taxane and carboplatin (TC). Methods: We collected 207 HSOC slides registered in the Japanese Gynecology Oncology Group 3016 (JGOG3016) study. Two of the authors, R.M. and I.K., classified the samples into the four pathological subtypes (n=201). We categorized the patients into two groups based on the treatment they received: ddTC (n=95) or TC (n=106). Progression free survival (PFS) was compared between the two groups for each pathological subtype. Results: Among the MT patients, the ddTC group had a significantly better PFS than the TC group (n= 30 vs 42, median survival: 1.8 vs 1.2 years, p=0.01). Among the SP patients, the ddTC group had better PFS than the TC group, even though the difference was not statistically significant (n=22 vs 27, median survival: 3.2 vs 1.4 years, p=0.08). In contrast, among the IR patients, the two groups showed no significant difference in PFS (n=16 vs 16, median survival: 5.2 vs 5.8 years, p=0.64). The PG patients also showed no significant difference in PFS between the two groups (n=27 vs 21, median survival: 1.5 and 1.7 years, p=0.64). Conclusions: The HSOC of MT type is more responsive to ddTC than to TC. This new pathological classification reflecting HSOC transcriptome subtypes leads to individualization of chemotherapy treatments.