Primary tumor chemosensitivity plays an important but poorly understood role in the ovarian cancer patient prognosis. The modeled CA-125 kinetic parameter (KELIM) is an indicator of chemosensitivity, and is associated with survival (Clin Cancer Res 2019 & 2020; JNCI CS 2020). The objective was to assess the role of KELIM regarding the probability of long progression-free survivorship (PS) > 5 years after 1st line treatment.
The datasets from 3 phase III trials in adjuvant setting (AGO-OVAR 9; AGO-OVAR 7 and ICON 7) were analyzed to explore the prognostic role of KELIM regarding the probability of PS in 2,868 stage (st) I-IV patients. An independent population-based cohort of 1,582 st II-IV patients in neo-adjuvant setting from The Netherlands Cancer Registry (NCR) was used as a validation dataset.
Of 2,868 patients in the learning set (median 45-month follow-up), 82 patients (2.8%) were PS: 48 st I-II (PS probability (PSp) = 9.5%); 32 st III (PSp = 1.6%); 2 st IV (PSp = 0.5%). With favorable KELIM > 0.06 days-1, PSp increased to 12.0% for st I-II, 2.9% for st III & 2.1% for st IV. In multivariable logistic regression, higher FIGO stage (st I-II reference; st III, OR = 0.18 and st IV: OR = 0.06) and KELIM (OR = 2.35 [1.51-3.59]) were predictors of PS. Of 1,582 patients in the NCR dataset (median 95-month follow-up), 36 patients (2.7%) were PS: 2 st II (PSp = 22.2%); 26 st III (PSp = 2.8%); 8 st IV (PSp = 1.2%). With favorable KELIM, PSp increased to 5.4% for st III, and 2.4% for st IV. In multivariable regression, completeness of interval debulking surgery (OR = 6.25 [2.40-21.41]) and KELIM (OR = 3.82 [1.49-9.65]) were predictors of PS. PSp was 12% for st III with favorable KELIM and complete surgery. In an explorative set with 509 patients, the KELIM prognostic impact was more marked in BRCA wild-type and BRCA1 mutated patients, than in BRCA2.
KELIM is an independent prognostic factor of progression-free survivorship > 5 years after 1st line treatment. The PSp is doubled in patients with favorable KELIM. The respective impacts of chemosensitivity and surgery relative to chance of potential cure are better understood.
Clinical trial identification
Legal entity responsible for the study
Dutch Cancer Society [IKNL2014-6838].
B. You: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Advisory/Consultancy: Bayer; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Clovis; Advisory/Consultancy: Amgen; Advisory/Consultancy: MSD; Advisory/Consultancy: ECS Progastrin. R. Kruitwagen: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche. A. du Bois: Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: GSK; Advisory/Consultancy: Clovis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Biocad; Advisory/Consultancy: Genmab/ Seattle Genetics; Advisory/Consultancy: MSD. F. Selle: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AZ; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: GSK; Honoraria (self), Speaker Bureau/Expert testimony: Clovis; Honoraria (self), Travel/Accommodation/Expenses: PharmaMar; Travel/Accommodation/Expenses: MSD. All other authors have declared no conflicts of interest.