In the field of ovarian cancer maintenance therapy, several landmark studies have pointed the way for clinical practice:

GOG-0218 trial: The first to confirm the maintenance therapeutic value of the anti-angiogenic drug bevacizumab (VEGFi), laying the foundation for subsequent exploration of combination therapy.

SOLO1 trial: Focusing on patients with BRCA mutations, it was confirmed that maintenance therapy with the PARP inhibitor olaparib monotherapy can significantly prolong progression-free survival (PFS), and the 5-year follow-up data further verifies its long-term benefits.

PRIMA trial: Expanding the indication of niraparib (PARPi) to the entire population, regardless of whether patients have homology recombination deficiency (HRD) or not, can benefit from maintenance therapy.

PAOLA-1 trial: The first exploration of a combined maintenance strategy, for HRD-positive patients, bevacizumab combined with olaparib significantly improved PFS compared with bevacizumab alone; Overall survival (OS) benefit was also observed in the BRCA mutation subgroup, but HRD-negative patients did not show a combined advantage.

However, the PAOLA-1 trial did not set up a PARP inhibitor monotherapy control group, so the core question of whether combination therapy is better than single agent has always lacked direct evidence to support it.

The recent FZOCUS-1 trial published in CA explored the maintenance treatment effect of the PARP inhibitor fluzoparib monotherapy or the combination of the anti-angiogenic drug apatinib for Chinese ovarian cancer patients, providing a new reference for clinical practice:

Trial design: Patients were stratified by BRCA mutation and response to first-line treatment, and randomly divided into three groups: fluzoparib+apatinib, fluzoparib+placebo, placebo+placebo.

Core results: Fluzoparib monotherapy (HR=0.58) or fluzoparib combined with apatinib (HR=0.57) significantly improved PFS compared with placebo, but there was no statistical difference between the two groups.

Subgroup analysis: BRCA mutation, HRD positive and the whole population, combination drugs did not show significant advantages over single drugs. Only in HRD-negative (HRP) populations, combination therapy showed an improvement in PFS (11 months vs. 16.6 months in the monotherapy group, HR=0.73), but it was not statistically significant.

Although the FZOCUS-1 trial explored combination strategies, the results did not confirm its superiority over monotherapy, and there may be multiple reasons behind it:

Differences in drug selection: Apatinib was selected as a VEGFi class of drugs in trials, while bevacizumab is more commonly used in clinical practice, and the efficacy and toxicity of the two in ovarian cancer have not been directly compared and cannot be completely equivalent.

Drug interactions: Early studies found that the combination of fluzoparib and apatinib resulted in a 48%-65% reduction in apatinib exposure, and a 33% reduction in the starting dose of fluzoparib in the trial to avoid toxicity stacking. Previous olaparib studies have shown that insufficient dose can directly affect the efficacy, which may weaken the advantages of combination therapy.

Limitations of beneficiary populations: The potential benefits of combination therapy may be concentrated only in specific populations such as HRP, but the benefit of this subgroup in the FZOCUS-1 trial is not statistically significant and a larger sample size is still needed to be validated.

Based on the available evidence, the choice of ovarian cancer maintenance therapy should follow the principle of "individualization", with the core reference to the patient's molecular characteristics (e.g., BRCA mutation, HRD status) and physical condition:

Patients with HRD-positive/BRCA mutations: PARP inhibitor monotherapy is currently the preferred regimen, with clear efficacy and controllable safety. If the patient has a high risk of recurrence (eg, residual disease, high tumor burden), the combination of bevacizumab can be considered after physician evaluation, but the benefits and toxicities need to be weighed.

HRD-negative/HRP patients: PARP inhibitors alone may still be beneficial, and combination therapy may be an alternative, but caution should be evaluated. Current evidence suggests a modest advantage and may increase adverse effects (eg, hypertension, proteinuria).

Special considerations: Drug interactions and dose adjustments in combination therapy need to be paid attention to to avoid insufficient drug exposure affecting the efficacy, and toxicity needs to be closely monitored.

At present, it is not fully clear whether PARP inhibitors combined with VEGFi are better than single agents, and a number of ongoing clinical trials are expected to further solve the puzzle, including:

Nirvana trial: Niraparib monotherapy compared to niraparib + bevacizumab;

AGO-OVAR 28 trial: also focusing on the efficacy of niraparib monotherapy and bevacizumab;

MITO 25 trial: The design is more complex, comparing three regimens: bevacizumab monotherapy, bevacizumab + rucaparib, and rucaparib monotherapy.

These trials will provide more conclusive evidence for the value of combination therapy through direct comparison, and future ovarian cancer maintenance therapy is expected to achieve more accurate population stratification and regimen selection.