Efficacy of subsequent therapies in patients with advanced ovarian cancer who relapse after first-line olaparib maintenance: results of the PAOLA-1/ENGOT-ov25 trial.

Understanding the efficacy of first subsequent therapy (FST) in patients experiencing disease progression in the first-line setting is important to optimize postprogression treatments.

了解一线治疗后疾病进展患者接受的首次后续治疗(FST)的效果对于优化疾病进展后的治疗至关重要。

We evaluated the efficacy of FST in patients from PAOLA-1/ENGOT-ov25 (NCT02477644) who received first-line olaparib maintenance.

我们评估了在PAOLA-1/ENGOT-ov25 (NCT02477644)中接受一线奥拉帕利维持治疗的患者中FST的疗效。

patients_and_methods

This post hoc analysis evaluated the efficacy of subsequent chemotherapy following disease progression by assessing time from FST to second subsequent therapy (SST) according to whether progression occurred during versus after first-line olaparib maintenance and FST type.

这项事后分析评估了疾病进展后接受后续化疗的疗效，通过评估从FST到第二次后续治疗(SST)的时间，根据疾病进展是在一线奥拉帕利维持治疗期间还是之后，以及FST类型。

A multivariate Cox model was used in the olaparib plus bevacizumab arm to identify prognostic factors influencing the efficacy of subsequent chemotherapy.

在奥拉帕利联合贝伐单抗组中，使用了多变量Cox模型来识别影响后续化疗疗效的预后因素。

Results

Of 806 randomized patients, 544 (67.5%) progressed and received subsequent chemotherapy.

在806名随机患者中，有544名（67.5%）病情进展并接受了后续化疗。

The median time from FST to SST was shorter in patients in the olaparib plus bevacizumab arm who progressed during first-line olaparib maintenance (6.1 months) than in those who progressed after first-line olaparib maintenance (11.4 months).

在奥拉帕利加贝伐单抗组中，首次奥拉帕利维持治疗期间进展的患者的FST至SST的中位时间（6.1个月）比首次奥拉帕利维持治疗后进展的患者短（11.4个月）。

Multivariate analysis indicated that progression after (versus during) first-line olaparib maintenance influenced time from FST to SST (hazard ratio0.65, 95% confidence interval0.50-0.84; P = 0.0011) independently of platinum-free interval or clinical risk.

多变量分析表明，首次奥拉帕利维持治疗后进展（与期间进展相比）影响了从FST到SST的时间（风险比0.65，95%置信区间0.50-0.84；P = 0.0011），这一影响与铂类药物无进展间隔或临床风险无关。

Among patients who progressed and received platinum-based chemotherapy with a PARP inhibitor as FST, the efficacy of subsequent therapies was also dependent on whether progression occurred during versus after first-line olaparib maintenance.

在接受基于铂类化疗和PARP抑制剂作为后续治疗的患者中，后续治疗的效果也取决于疾病进展是在一线奥拉帕利维持治疗期间还是之后发生的。

Conclusions

These results suggest that the timing of disease progression relative to first-line olaparib maintenance may impact the efficacy of subsequent platinum-based chemotherapy.

这些结果表明，疾病进展相对于一线奥拉帕利维持治疗的时间可能会影响后续基于铂类化疗的效果。

Although results should be interpreted with caution, across all subgroups, including patients who received platinum-based chemotherapy with PARP inhibitor rechallenge as FST, the median time from FST to SST was longer if progression occurred after versus during first-line olaparib maintenance.

尽管结果需谨慎解释，但所有亚组中，包括接受铂类化疗联合PARP抑制剂作为FST（后续治疗）的患者，如果疾病进展发生在首次使用奥拉帕利维持治疗之后，而非期间，从FST到SST（第二次治疗）的中位时间更长。