Abstract 3433
Background
Tumour Microvessel density (MVD) is often used as a surrogate marker for tumoral angiogenic activity. In the randomized phase II neo-adjuvant CHIVA trial, ovarian cancer patients (pts) treated with standard chemotherapy plus Nintedanib (Ni) compared to chemotherapy alone had a reduced rate of complete surgical resection at interval debulking surgery (IDS), worse PFS and OS. To explain these results we assessed the predictive/prognostic value of MVD at baseline and the MVD decrease from baseline to IDS.
Methods
Paired tumours from baseline and IDS were available from 79/188 randomized pts. A total of 158 virtual slides of immunostained tumor section with anti-CD31 were analysed. MVD was quantified by an image processing on whole tumor section. MVD high level was defined as MVD > 33.5 vessel/mm² which is the highest Youden index on the ROC curve for PFS. The relationship between MVD at baseline and PFS and OS was evaluated using Kaplan-Meier survival estimates.
Results
Main characteristics of the 79 pts were similar to the overall CHIVA population: mean age (62 years), ECOG performance status = 0 (34%), high-grade serous histology (75%). At baseline, MVD was similar in both arms and was low for 35% and 30% of the pts in the Ni and control arm respectively. The rate of complete resection (CC0) was 56% in the Ni arm versus 70% in the control arm.
In the low MVD group median PFS was 13.3 months (95%CI 11 – 22.2) versus 17 months (95%CI 13.7 – 20.5) in the high MVD group (p = 0.85). In the low MVD group, PFS in the Ni and control arm were 12.8 (95%CI 10.7-22.2) and 21.3 months (95%CI 12.5-NA) respectively (p = 0.08). The corresponding PFS in the high MVD group were 18.0 (95%CI 14.4-21.6) vs 14.5 months (95%CI 12.4-22.5) (p = 0.22). No difference was observed for OS. Baseline MVD was not associated with the rate of CC0. There was no significant difference in the decrease of MVD at IDS between the Ni arm (38% of the pts) and the control arm (48%, p = 0.4).
Conclusions
The negative impact of Nintedanib in patients with low baseline MVD tumours may be one explanation of the poor PFS rate observed in the Nintedanib arm of the CHIVA trial.
Clinical trial identification
2011-006288-23.
Editorial acknowledgement
Legal entity responsible for the study
ARCAGY-GINECO.
Funding
Health ministry grants( PHRC).
Disclosure
C. Blanc-Fournier: Honoraria (self): Roche. N. Raban: Travel / Accommodation / Expenses: Roche. G. Ferron: Honoraria (self): Olympus Europe; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Roche. A. Floquet: Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche. J. Alexandre: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self): PharmaMar; Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen. C. Louvet: Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Servier; Advisory / Consultancy: AstraZeneca. J. Florence: Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy: Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Sanofi; Travel / Accommodation / Expenses: Janssen. All other authors have declared no conflicts of interest.
Resources from the same session
3516 - Palbociclib Rechallenge in Hormone Receptor (HR)[+]/HER2[-] Advanced Breast Cancer (ABC). PALMIRA Trial
Presenter: Antonio Llombart Cussac
Session: Poster Display session 2
Resources:
Abstract
4616 - Alpelisib (ALP) + Endocrine Therapy (ET) by Last Prior Therapy in Patients (pts) With PIK3CA-Mutated Hormone-Receptor Positive (HR+) Human Epidermal Growth Factor Receptor-2-Negative (HER2–) Advanced Breast Cancer (ABC): Additional Study Cohort in BYLieve
Presenter: Eva Ciruelos
Session: Poster Display session 2
Resources:
Abstract
3592 - PRECYCLE: Impact of CANKADO-based eHealth-support on quality of life in metastatic breast cancer patients treated with palbociclib and endocrine therapy.
Presenter: Tom Degenhardt
Session: Poster Display session 2
Resources:
Abstract
4168 - Efficacy and safety of oral poly (ADP-ribose) polymerase inhibitor fluzoparib in patients with BRCA1/2 mutations and platinum sensitive recurrent ovarian cancer
Presenter: Ning Li
Session: Poster Display session 2
Resources:
Abstract
2785 - Effect of response to last platinum-based chemotherapy in patients (pts) with platinum-sensitive, recurrent ovarian carcinoma in the phase 3 study ARIEL3 of rucaparib maintenance treatment
Presenter: Jonathan Ledermann
Session: Poster Display session 2
Resources:
Abstract
3496 - Integrated safety analysis of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib in patients (pts) with ovarian cancer in the treatment and maintenance settings
Presenter: Rebecca Kristeleit
Session: Poster Display session 2
Resources:
Abstract
2844 - Clinical factors associated with prolonged response and survival under olaparib as maintenance therapy in BRCA mutated ovarian cancers
Presenter: S.Intidhar Labidi-Galy
Session: Poster Display session 2
Resources:
Abstract
1955 - A Prospective Evaluation of Tolerability of Niraparib Dosing Based on Baseline Body Weight (BW) and Platelet (plt) Count: Blinded Pooled Interim Safety Data from the NORA Study
Presenter: Xiaohua Wu
Session: Poster Display session 2
Resources:
Abstract
2539 - Evaluation of Niraparib 200 mg/d as Maintenance Therapy in Recurrent Ovarian Cancer and Associated Thrombocytopenia in a Real-World US Setting
Presenter: Premal Thaker
Session: Poster Display session 2
Resources:
Abstract
1290 - Niraparib initial dose and its’ management in patients with recurrent high-grade serous ovarian cancer.
Presenter: Jacek Grabowski
Session: Poster Display session 2
Resources:
Abstract