Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 May;32(3):e37.
doi: 10.3802/jgo.2021.32.e37.

Primary platinum resistance and its prognostic impact in patients with recurrent ovarian cancer: an analysis of three prospective trials from the NOGGO study group

Fabian Trillsch  1 , Sven Mahner  2 , Bastian Czogalla  2 , Miriam Rottmann  3 , Radoslav Chekerov  4 , Elena Ioana Braicu  4 , Gülten Oskay-Öczelik  5 , Pauline Wimberger  6 , Rolf Richter  4 , Jalid Sehouli  4
Affiliations
Meta-Analysis

Primary platinum resistance and its prognostic impact in patients with recurrent ovarian cancer: an analysis of three prospective trials from the NOGGO study group

Fabian Trillsch et al. J Gynecol Oncol. 2021 May.

Abstract

Objective: Patients with platinum-resistant ovarian cancer (PROC) have a high need for reliable prognostic markers. Since significance of primary platinum resistance (PPR) versus secondary platinum resistance (SPR) was identified for patients receiving anti-angiogenic therapy, it has not been confirmed for chemotherapy only.

Methods: PROC patients from 3 prospective trials of the NOGGO study group (TOWER, NOGGO-Treosulfan, and TRIAS) were included in this meta-analysis. Exploratory Cox and logistic regression analyses were performed to correlate progression-free survival (PFS) and overall survival (OS) with the timing when platinum resistance developed.

Results: Of 477 patients, 264 (55.3%) were classified as PPR, compared to 213 (44.7%) with SPR. For patients receiving chemotherapy only, SPR was associated with a significantly longer median PFS of 3.9 compared to 3.1 months for PPR (hazard ratio [HR]=0.78; p=0.015). SPR versus PPR was confirmed to be an independent prognostic factor for better PFS in multivariate analysis (HR=0.74; p=0.029). Benefit from adding sorafenib to chemotherapy was mainly seen in PPR (HR=0.40; p<0.001) compared to SPR patients (HR=0.83; p=0.465).

Conclusions: Prognostic significance of SPR versus PPR could be elucidated for patients receiving chemotherapy only. In contrast to bevacizumab, the multi-kinase inhibitor sorafenib exhibits profound therapeutic efficacy in PPR patients indicating potential to overcome this negative prognostic impact.

Keywords: Anti-angiogenic Treatment; Mono-chemotherapy; Primary Platinum Resistance; Prognostic Factor; Recurrent Ovarian Cancer; Sorafenib.

PubMed Disclaimer

Conflict of interest statement

Fabian Trillsch: grants and personal fees from AstraZeneca, Clovis, Medac, MSD, PharmaMar, Roche, and Tesaro/GSK. Sven Mahner: grants and personal fees from AstraZeneca, Clovis, Medac, Novartis, Olympus Europe, PharmaMar, Pfizer, Roche, Sensor Kinesis, Tesaro/GSK, and TEVA. Pauline Wimberger: grants and personal fees from AstraZeneca, Amgen, Clovis, Medac, MSD, Pfizer, PharmaMar, Roche, Tesaro/GSK, Novartis, Eisai, Celgene and TEVA. Jalid Sehouli: grants and personal fees from Astra Zeneca, Bayer, Eisai, Clovis, Olympus, Johnsons and Johnson, PharmaMar, Pfizer, TEVA, Tesaro/GSK, MSD, Lilly, Roche and Merck. All remaining authors have declared no conflicts of interest.

Figures

Fig. 1
Fig. 1. PFS according to time to development of platinum resistance (PPR vs. SPR) in patients form all 3 trials. Kaplan-Meier curves regarding PFS for patients with PPR compared to SPR in the overall cohort from all 3 trials (A, n=477) and in the overall cohort excluding patients who received sorafenib within TRIAS (B, n=394).
CI, confidence interval; HR, hazard ratio; PFS, progression-free survival; PPR, primary platinum-resistant; SPR, secondary platinum-resistant.
Fig. 2
Fig. 2. PFS and OS according to time to development of platinum resistance (PPR vs. SPR) in the TRIAS cohort (n=172). Kaplan-Meier curves comparing PPR with SPR regarding PFS and OS in patients receiving placebo plus chemotherapy (A) and sorafenib plus chemotherapy (B).
CI, confidence interval; HR, hazard ratio; OS, overall survival; PFS, progression-free survival; PPR, primary platinum-resistant; SPR, secondary platinum-resistant.
Fig. 3
Fig. 3. PFS and OS according to treatment in the PPR and SPR subgroups of the TRIAS cohort (n=172).
Kaplan-Meier curves comparing treatment (placebo plus chemotherapy vs sorafenib plus chemotherapy) regarding PFS and OS in PPR patients (A) and in SPR patients (B). CI, confidence interval; HR, hazard ratio; OS, overall survival; PFS, progression-free survival; PPR, primary platinum-resistant; SPR, secondary platinum-resistant.
See this image and copyright information in PMC

References

    1. Wilson MK, Pujade-Lauraine E, Aoki D, Mirza MR, Lorusso D, Oza AM, et al. Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: recurrent disease. Ann Oncol. 2017;28:727–732. - PMC - PubMed
    1. Colombo N, Sessa C, Bois AD, Ledermann J, McCluggage WG, McNeish I, et al. ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. Int J Gynecol Cancer. 2019 - PubMed
    1. Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001;19:3312–3322. - PubMed
    1. Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD, et al. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007;25:2811–2818. - PubMed
    1. ten Bokkel Huinink W, Gore M, Carmichael J, Gordon A, Malfetano J, Hudson I, et al. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol. 1997;15:2183–2193. - PubMed

Publication types

MeSH terms