Elsevier

Gynecologic Oncology

Volume 154, Issue 2, August 2019, Pages 441-448
Gynecologic Oncology

Review Article
Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data

https://doi.org/10.1016/j.ygyno.2019.04.679Get rights and content
Under a Creative Commons license
open access

Highlights

  • The Chemotherapy response score (CRS) assesses histological effect in ovarian cancer after neoadjuvant chemotherapy (NACT).

  • The CRS is associated with progression-free and overall survival.

  • CRS could provide useful information to estimate a patient's probability of early vs. late relapse.

  • The CRS is an appealing primary endpoint in clinical trials as a surrogate for survival as it can be measured earlier.

  • We recommend the CRS be incorporated as an endpoint in clinical trials of novel therapeutic agents that have a NACT arm.

Abstract

Objective

There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT.

Methods

We established an international collaboration to conduct a systematic review and meta-analysis, pooling individual patient data from 16 sites in 11 countries. Patients had stage IIIC/IV HGSC, 3–4 NACT cycles and >6-months follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and progression free and overall survival (PFS and OS).

Results

877 patients were included from published and unpublished studies. Median PFS and OS were 15 months (IQR 5–65) and 28 months (IQR 7–92) respectively. CRS3 was seen in 249 patients (28%). The pooled hazard ratios (HR) for PFS and OS for CRS3 versus CRS1/CRS2 were 0·55 (95% CI, 0·45–0·66; P < 0·001) and 0·65 (95% CI 0·50–0·85, P = 0·002) respectively; no heterogeneity was identified (PFS: Q = 6·42, P = 0·698, I2 = 0·0%; OS: Q = 6·89, P = 0·648, I2 = 0·0%). CRS was significantly associated with PFS and OS in multivariate models adjusting for age and stage. Of 306 patients with known germline BRCA1/2 status, those with BRCA1/2 mutations (n = 80) were more likely to achieve CRS3 (P = 0·027).

Conclusions

CRS3 was significantly associated with improved PFS and OS compared to CRS1/2. This validation of CRS in a real-world setting demonstrates it to be a robust and reproducible biomarker with potential to be incorporated into therapeutic decision-making and clinical trial design.

Keywords

Neoadjuvant chemotherapy
Chemotherapy response score
Prognosis
High-grade serous tubo-ovarian cancer

Cited by (0)

1

PC and AP contributed equally.