Neoadjuvant chemotherapy with or without nintedanib for advanced epithelial ovarian cancer: Lessons from the GINECO double-blind randomized phase II CHIVA trial

Ferron, Gwénaël; Rauglaudre, Gaëtan De; Becourt, Stéphanie; Delanoy, Nicolas; Joly, Florence; Lortholary, Alain; You, Benoît; Bouchaert, P.; Malaurie, E.; Gouy, Sébastien; Kaminsky, Marie‐Christine; Meunier, Jérôme; Alexandre, Jérôme; Berton, Dominique; Dohollou, N.; Dubot, Coraline; Floquet, Anne; Favier, Laure; Vénat-Bouvet, Laurence; Fabbro, Michel; Louvet, Christophe; Lotz, Jean‐Pierre; Abadie‐Lacourtoisie, Sophie; Desauw, Christophe; Piano, Francesco Del; Leheurteur, Marianne; Bonichon-Lamichhane, Nathalie; Rastkhah, Mansour; Follana, Philippe; Gantzer, Justine; Ray‐Coquard, Isabelle; Pujade-Lauraine, Éric

doi:10.1016/j.ygyno.2023.01.008

Cited by 10 publications

(10 citation statements)

References 17 publications

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“…Upon detailed examination, 51 studies were deemed unfit for inclusion: 5 were single-arm clinical trials; 2 were non-comparative clinical studies; 3 trials included duplicate patient data; 23 trials exhibited intervention and control designs that did not align with the inclusion criteria; and 18 articles failed to report the necessary outcome data. Finally, 35 RCTs were selected for inclusion in the meta-analysis ( Aghajanian et al, 2012 ; Aghajanian et al, 2015 ; Burger et al, 2011 ; Chekerov et al, 2018 ; Coleman et al, 2017 ; du Bois et al, 2014 ; du Bois et al, 2016 ; Duska et al, 2020 ; Ferron et al, 2023 ; Gore et al, 2019 ; Gotlieb et al, 2012 ; Hall et al, 2020 ; Herzog et al, 2013 ; Karlan et al, 2012 ; Kim et al, 2018 ; Ledermann et al, 2021 ; Ledermann et al, 2016 ; Ledermann et al, 2011 ; Liu et al, 2019 ; Liu et al, 2022 ; Marth et al, 2017 ; Monk et al, 2016b ; Nicum et al, 2024 ; Oza et al, 2015 ; Pignata et al, 2021 ; Pignata et al, 2015 ; Pujade-Lauraine et al, 2014 ; Ray-Coquard et al, 2020 ; Richardson et al, 2018 ; Roque et al, 2022 ; Shoji et al, 2022 ; Tewari et al, 2019 ; Vergote et al, 2019a ; Vergote et al, 2019b ; Wang et al, 2022 ) ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Similarly, the consolidated results from a fixed-effects model (I 2 = 8.6%, Tau 2 = 0.0027), derived from 6 RCTs, revealed that anti-angiogenic drug monotherapy did not significantly enhance OS (HR [95% CI] = 1.039 [0.921–1.173], 95% PI: 0.824–1.331). A single study reported on the ORR associated with monotherapy ( Ferron et al, 2023 ), revealing a lower ORR with the use of anti-angiogenic monotherapy (specifically nintedanib) as compared to placebo (RR [95% CI] = 0.628 [0.447–0.882]). Concerning AEs, pooled results from 3 trials suggested that the incidence of any grade AEs was significantly higher with anti-angiogenic monotherapy compared to placebo (RR [95% CI] = 1.072 [1.036–1.109], 95% PI: 0.709–1.592; I 2 = 40.1%, Tau 2 = 0.0006).…”

Section: Resultsmentioning

confidence: 99%

“…However, there is a lack of a comprehensive meta-analysis to evaluate the effects of monotherapy or combination therapy with anti-angiogenic drugs on OC. Moreover, multiple RCTs have published the latest relevant clinical results in recent years ( Liu et al, 2022 ; Roque et al, 2022 ; Ferron et al, 2023 ; Nicum et al, 2024 ). Therefore, we conducted a meta-analysis to systematically assess the efficacy and safety of anti-angiogenic drug monotherapy or combined with chemotherapy or PARP inhibitors in the treatment of OC.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of anti-angiogenic drug monotherapy and combination therapy for ovarian cancer: a meta-analysis and trial sequential analysis of randomized controlled trials

Xie,

Zhou

2024

Front. Pharmacol.

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BackgroundAs the development of novel anti-angiogenic drugs and the continuous evolution of guideline recommendations, the efficacy and safety of anti-angiogenic agents in ovarian cancer (OC) remains unclear. Consequently, a meta-analysis was carried out to assess the efficacy and safety of anti-angiogenic drug monotherapy and combination therapy for OC.MethodsAn exhaustive literature review was performed across multiple databases, including PubMed, Embase, Web of Science, and Cochrane, encompassing all relevant randomized controlled trials (RCTs) up until 6 April 2024. The evaluation of efficacy outcomes incorporated progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Safety was assessed through the occurrence of any grade adverse events (AEs) and grade ≥3 AEs. Synthesis of the data involved the calculation of hazard ratios (HRs), relative risks (RRs), and their corresponding 95% confidence intervals (CIs) and prediction intervals (PIs). Trial sequential analysis was executed employing TSA v0.9.5.10 Beta software, STATA 12.0, and R software 4.3.1.ResultsIn this meta-analysis, 35 RCTs were included, encompassing 16,199 subjects in total. The overall analysis indicated that anti-angiogenic drug combination therapy significantly improved PFS (HR [95% CI] = 0.678 [0.606–0.759], 95% PI: 0.415–1.108), OS (HR [95% CI] = 0.917 [0.870–0.966], 95% PI: 0.851–0.984), and ORR (RR [95% CI] = 1.441 [1.287–1.614], 95% PI: 1.032–2.014), but also increased the incidence of grade ≥3 AEs (RR [95% CI] = 1.137 [1.099–1.177], 95% PI: 1.011–1.252). The analysis did not corroborate any benefit of anti-angiogenic monotherapy over placebo concerning PFS (HR [95% CI] = 0.956 [0.709–1.288], 95% PI: 0.345–2.645) and OS (HR [95% CI] = 1.039 [0.921–1.173], 95% PI: 0.824–1.331). However, it was observed that monotherapy with anti-angiogenic drugs did increase the incidence of any grade AEs (RR [95% CI] = 1.072 [1.036–1.109], 95% PI: 0.709–1.592).ConclusionOur study confirmed the PFS, OS, and ORR benefits of anti-angiogenic drug combination therapy for OC patients. The efficacy results of anti-angiogenic monotherapy necessitates further evaluation as more RCTs become available. Clinicians should be vigilant of AEs when administering anti-angiogenic agents in a clinical setting.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of anti-angiogenic drug monotherapy and combination therapy for ovarian cancer: a meta-analysis and trial sequential analysis of randomized controlled trials

Xie,

Zhou

2024

Front. Pharmacol.

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“…Nintedanib is known to cause common adverse events such as diarrhea ( 110 ). Nevertheless, phase 3 trials have exhibited remarkable therapeutic effects when nintedanib is combined with chemotherapy such as carboplatin and paclitaxel in ovarian cancer patients, although serious adverse gastrointestinal events accompany these positive effects ( 111 – 113 ).…”

Section: Anti-angiogenesis Therapy For Ovarian Cancermentioning

confidence: 99%

Vascular normalization: reshaping the tumor microenvironment and augmenting antitumor immunity for ovarian cancer

Yu,

Wang,

Yuan

et al. 2023

Front. Immunol.

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Ovarian cancer remains a challenging disease with limited treatment options and poor prognosis. The tumor microenvironment (TME) plays a crucial role in tumor growth, progression, and therapy response. One characteristic feature of the TME is the abnormal tumor vasculature, which is associated with inadequate blood perfusion, hypoxia, and immune evasion. Vascular normalization, a therapeutic strategy aiming to rectify the abnormal tumor vasculature, has emerged as a promising approach to reshape the TME, enhance antitumor immunity, and synergize with immunotherapy in ovarian cancer. This review paper provides a comprehensive overview of vascular normalization and its potential implications in ovarian cancer. In this review, we summarize the intricate interplay between anti-angiogenesis and immune modulation, as well as ICI combined with anti-angiogenesis therapy in ovarian cancer. The compelling evidence discussed in this review contributes to the growing body of knowledge supporting the utilization of combination therapy as a promising treatment paradigm for ovarian cancer, paving the way for further clinical development and optimization of this therapeutic approach.

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“…Although bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, has demonstrated brief prolongation of PFS in patients with advanced epithelial ovarian cancer when incorporated with perioperative chemotherapy, the role of an oral anti‐angiogenic was previously unclear. The phase 2 CHIVA study (ClinicalTrials.gov identifier NCT01583322) investigated the combination of nintendanib (oral antiangiogenic agent) with neoadjuvant chemotherapy and demonstrated inferior PFS and OS with increased toxicity 46 …”

Section: Introductionmentioning

confidence: 99%

Top advances of the year: Ovarian cancer

Lumish,

Kohn,

Tew

2023

Cancer

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Although cure rates remain low and effective screening strategies are elusive, the recent advances in systemic therapies over the past year highlighted in this review have prolonged survival for women with ovarian cancer. In 2022, the first antibody–drug conjugate for platinum‐resistant ovarian cancer received accelerated US Food and Drug Administration (FDA) approval. Confirmatory studies examining the efficacy of mirvetuximab and other antibody–drug conjugates are underway. In the upfront setting, the first data establishing an overall survival benefit from poly(ADP‐ribose) polymerase inhibitor maintenance was demonstrated after a 7‐year follow‐up period. In contrast, long‐term updates from poly(ADP‐ribose) polymerase inhibitor trials in the noncurative setting reported survival detriments, and the FDA withdrew the respective indications. Several trials attempted to improve upon the standard of care for platinum‐sensitive ovarian carcinoma and those with rare ovarian cancer histologies (carcinosarcoma, clear cell carcinoma) but failed to demonstrate a clinically or statistically meaningful benefit. This leaves the open question of how to further optimize systemic therapy for advanced ovarian carcinoma to improve long‐term survival and cure rates.

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Neoadjuvant chemotherapy with or without nintedanib for advanced epithelial ovarian cancer: Lessons from the GINECO double-blind randomized phase II CHIVA trial

Cited by 10 publications

References 17 publications

Efficacy and safety of anti-angiogenic drug monotherapy and combination therapy for ovarian cancer: a meta-analysis and trial sequential analysis of randomized controlled trials

Efficacy and safety of anti-angiogenic drug monotherapy and combination therapy for ovarian cancer: a meta-analysis and trial sequential analysis of randomized controlled trials

Vascular normalization: reshaping the tumor microenvironment and augmenting antitumor immunity for ovarian cancer

Top advances of the year: Ovarian cancer

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