Fuzuloparib with or without apatinib as maintenance therapy in newly diagnosed, advanced ovarian cancer (FZOCUS‐1): A multicenter, randomized, double‐blind, placebo‐controlled phase 3 trial

Lingying Wu; Jing Wang; Qingshui Li; Danbo Wang; Cuiying Zhang

doi:10.3322/caac.70042

Fuzuloparib with or without apatinib as maintenance therapy in newly diagnosed, advanced ovarian cancer (FZOCUS‐1): A multicenter, randomized, double‐blind, placebo‐controlled phase 3 trial

Lingying Wu, Jing Wang, Qingshui Li, Danbo Wang, Cuiying Zhang, Junying Tang, Guonan Zhang, Min Hao, Desheng Yao, Qinglei Gao, Youzhong Zhang, Ruifang An, Ru-tie Yin, Li Wang, Bairong Xia...

Wiley (2025) • Volume 76, Issue 1, Pages e70042-e70042

Empirical-ClinicalRCTPDF AvailableGrade EligiblePre-registered (registry)⚠️ High Risk Flags⚠️ Moderate Risk Flags

Overall Assessment

Adequate Methodological Quality

Assessment created by PaperScores Medical AI v0.1.0 on Dec 14, 2025

C

64/100

Key Takeaways

•Both fuzuloparib and fuzuloparib+apatinib significantly improved PFS vs placebo (HR ~0.58).
•No added PFS benefit from adding apatinib in HRD/BRCA-mutated disease.
•HRP subgroup shows a non-significant trend favouring combination (HR 0.73; wide CI).
•Safety consistent with PARPi ± VEGFR2 inhibitor; more hypertension/proteinuria with apatinib.
•Registration ID inconsistency and no data sharing lower transparency.

Conclusion

Well-conducted, adequately powered RCT; clear PFS gains vs placebo. Combination not superior to PARPi in HRD; possible HRP signal merits confirmation.

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Quality Dimensions

Bias & Integrity

COI handling, outcome switching, selective reporting

D+50

Methods Rigour

Protocol clarity, sampling, controls

B+82

External Validity

Generalisability, setting, population

C62

Transparency & Reproducibility

Data/code/materials availability, preregistration

D-30

Significance & Novelty

Contribution vs prior art; context if known

B-72

Statistical Validity

Models, assumptions, multiplicity, CI priority

B78

Integrity & Transparency

Integrity checks

P-hacking risk?

?

None suspected

Signs of selective hypothesis testing or analysis choices that could inflate false positive rates.

Outcome switching?

?

None suspected

Evidence that primary outcomes were changed during or after the study, potentially distorting results.

Conflict of interest?

?

Serious concern

Authors have financial or other relationships that could bias research findings.

Data integrity issues?

?

Review recommended

Concerns about the accuracy, completeness, or authenticity of the reported data.

Open science signals

Research data

?

Not shared

Raw data used in the analyses is publicly available or accessible upon request.

Analysis code

?

Not shared

Code or scripts used to analyze the data are shared for reproducibility.

Study materials

?

Not shared

Protocols, questionnaires, and other materials are publicly available.

Premise

Primary Research Question

Does maintenance fuzuloparib±apatinib improve PFS vs placebo, and does apatinib add benefit over fuzuloparib, by HRD/BRCA status?

Hypothesis

PARPi (±antiangiogenic) superior to placebo; combination superior to PARPi alone, especially in BRCA/HRD.

Hypothesis is Falsifiable

✓Yes

Time-to-event primary endpoint with prespecified comparisons.

PICO Framework

Population✓Yes

FIGO III–IV epithelial OC in CR/PR post-platinum.

Intervention✓Yes

Fuzuloparib 100 mg bid + apatinib 375 mg qd (oral).

Comparison✓Yes

Fuzuloparib 150 mg bid + placebo, and double placebo.

Outcome✓Yes

BIRC-assessed PFS (RECIST 1.1); OS secondary.

Literature Positioning

Literature Review Balanced

Well covered

Cites PAOLA-1, OVARIO, PRIMA/PRIME/ATHENA-MONO/FLAMES, etc.

Evidence: Discussion, p. 7–9

Research Gap Clearly Stated

Well covered

States lack of prospective PARPi+antiangiogenic vs PARPi alone data.

Evidence: Introduction, p. 2

Stated Contribution Clear

Well covered

First phase 3 head-to-head comparison; reports final PFS.

Evidence: Discussion, p. 7

Study Provenance

Peer reviewed venueIndustry funding disclosedNo conflicts declaredAffiliations listed

Authors & Affiliations

57 Chinese centres; two authors affiliated with Jiangsu Hengrui Pharmaceuticals (affiliation 55).

Funding Statement

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Conflicts of Interest

The authors declare no conflicts of interest.

Peer Review

✓Published in CA: A Cancer Journal for Clinicians.

Evidence: p. 1 header

Methodological Assessment

Randomized Controlled TrialCONSORTRCT

16 applicable checklist items.

Yes 15 · Unclear 1

Study Design & Protocol

✓

Power Analysis Reported

Sample size and α-spending detailed with event targets.

Evidence: Methods: Statistical analysis, p. 4

✓

Randomisation Adequate

Central IWRS, block size 5; stratified by gBRCA status and response.

Evidence: Methods: Interventions, p. 4

✓

Allocation Concealment

Centralised IWRS implies concealment.

Evidence: Methods: Interventions, p. 4

✓

Blinding

Double-blind; BIRC independent.

Evidence: Title/Methods; End points p. 3

✓

Blinding Adequate

Placebo-controlled with matched oral agents.

Evidence: Methods: Interventions, p. 4

✓

Intervention Replicable

Doses and schedules specified for all arms.

Evidence: Methods: Interventions, p. 4

✓

Outcomes Pre-specified

Primary: BIRC PFS; OS and others secondary.

Evidence: Methods: End points, p. 3

✓

Pre-registration Evidence

ClinicalTrials.gov listed; albeit conflicting IDs reported.

Evidence: Intro p. 2; Methods p. 3

Analysis & Reporting

✓

Analysis Set Appropriate (ITT/mITT)

Efficacy analysed in ITT; safety as-treated.

Evidence: Methods: Statistical analysis, p. 4

?

Missing Data Handled Appropriately

Censoring described; no imputation/handling specifics.

Evidence: Methods: Statistical analysis, p. 4

✓

Baseline Balance Acceptable

Baseline characteristics balanced across arms.

Evidence: Table 1, p. 6

✓

Adherence Adequate

High relative dose intensity (~95%); durations reported.

Evidence: Safety, p. 10

✓

Participant Flow Reported (CONSORT)

CONSORT-style flow in Fig S3.

Evidence: Fig. S3 (Supp.)

✓

Harms Reported Adequately

TRAE tables incl. grade ≥3 and discontinuations.

Evidence: Tables 3–4, p. 10–11

✓

Cluster/Strata Accounted

Stratified log-rank/Cox by randomisation strata.

Evidence: Methods: Statistical analysis, p. 4

✓

Interim Analyses Handled

Lan–DeMets O’Brien–Fleming α spending; interim met.

Evidence: Methods: Statistical analysis, p. 4

Modules without applicable checklist items (9)

These designs were fully marked as not applicable but remain available for reference.

Abstract

Although poly(adenosine diphosphate‐ribose) polymerase inhibitors (PARPis) and bevacizumab were approved as first‐line maintenance for advanced ovarian cancer (OC), evidence comparing this combination with PARPi monotherapy, especially in BRCA ‐mutated/homologous recombination‐deficient (HRD) patients, is lacking. This study compared combined fuzuloparib (a PARPi) plus apatinib (a vascular endothelial growth factor receptor‐2 inhibitor) with either fuzuloparib or placebo as first‐line maintenance in patients with advanced OC. Patients who had newly diagnosed, advanced OC and responded to first‐line, platinum‐based chemotherapy were randomized 2:2:1 to receive combined fuzuloparib (100 mg twice daily) plus apatinib (375 mg daily), fuzuloparib (150 mg twice daily) plus placebo, or double‐placebo treatment. The primary end point was blinded independent review committee (BIRC)‐assessed progression‐free survival (PFS). Six hundred seventy‐four patients were randomized to receive fuzuloparib plus apatinib ( n = 269), fuzuloparib ( n = 269), or placebo ( n = 136). At the final analysis (November 1, 2024; 385 BIRC‐assessed PFS events; median follow‐up, 40 months), the median BIRC‐assessed PFS was 26.9 months with the combination versus placebo (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.44–0.75; one‐sided p < .0001) and 29.9 months with fuzuloparib monotherapy versus placebo (HR, 0.58; 95% CI, 0.44–0.75; one‐sided p < .0001) compared with 11.1 months with placebo. A PFS benefit was observed regardless of germline BRCA1/2 mutation status. In homologous recombination‐deficient patients (including those with BRCA1/2 mutations), combined fuzuloparib and apatinib produced a PFS similar to that of fuzuloparib (34.1 vs. 35.8 months, respectively); in homologous recombination‐proficient patients, PFS had a trend favoring the combination (16.6 vs. 11.0 months; HR, 0.73; 95% CI, 0.45–1.19). Both treatments were well tolerated. Overall survival was immature. Both fuzuloparib and combination therapy improved PFS compared with placebo as maintenance therapy for patients who had newly diagnosed, advanced OC. Adding apatinib to fuzuloparib did not prolong PFS among homologous recombination‐deficient patients. There was a PFS benefit trend among homologous recombination‐proficient patients who received combination therapy compared with those who received monotherapy.

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Study Overview

Study Design

RCT

Primary classification used to evaluate this research.

Population

Adults (18–75) with newly diagnosed FIGO III–IV ovarian/fallopian/peritoneal cancer in CR/PR after platinum chemo, China, 57 sites.

Brief summary of who or what was studied.

Sample Size

674

Number of participants included in the study analyses.

Study Arms

3 arms

Total number of intervention or comparison groups.

Pre-registration

Registered in a public registry

Indicates whether the protocol or trial was registered before data collection.

Randomisation

Blocked randomisation

How participants were allocated to groups: None (no randomisation), Simple (random order), Blocked (groups balanced in blocks), Stratified (balanced within subgroups), Adaptive (allocation adjusted based on previous enrollments).

Blinding

Double blind

Who was unaware of group assignments: None (everyone knew), Single blind (participants didn't know their group), Double blind (participants and researchers didn't know), Triple blind (also outcome assessors didn't know).

Analysis Set

ITT (all randomised participants)

Which participants were included in analysis: ITT (all randomized, regardless of adherence), mITT (modified ITT, excluding some for valid reasons), Per protocol (only those who completed as planned), As treated (grouped by actual treatment received), Other (alternative approach).

Follow-up

median 40 months

Duration of observation or follow-up for outcomes.

Primary Outcome

Primary outcome was pre-specified in the protocol or registry.

Effect Size

HR for BIRC-assessed PFS vs placebo: HR 0.58 (95% CI 0.44–0.75) fuzuloparib vs placebo; HR 0.57 (95% CI 0.44–0.75) combo vs placebo

Reviewer Notes

Phase 3 multicentre randomised, double-blind, placebo-controlled parallel-group trial; efficacy analysed ITT.

Publication Details

DOI

10.3322/caac.70042

Published

November 25, 2025

Citations

0 citations

External Resources

DOI Link OpenAlex

Disclaimer: This assessment is generated by AI and should not be the sole basis for clinical or research decisions. Always review the original paper and consult with domain experts.

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