KEYLYNK-009: Pembrolizumab plus Olaparib in Locally Recurrent Inoperable or Metastatic Triple-Negative Breast Cancer after Clinical Benefit from First-Line Pembrolizumab plus Chemotherapy.

patients_and_methods

In this phase 2 study (NCT04191135), participants with previously untreated locally recurrent inoperable/metastatic TNBC received first-line pembrolizumab 200 mg once every 3 weeks plus platinum-based chemotherapy.

在这项II期研究（NCT04191135）中，之前未接受过治疗的局部复发性/不可手术/转移性三阴性乳腺癌患者接受了每3周一次的200毫克帕博利珠单抗作为一线治疗，同时联合铂类化疗。

Participants with complete/partial response or stable disease (per RECIST v1.1) were randomly assigned 1:1 to pembrolizumab 200 mg once every 3 weeks plus olaparib 300 mg twice a day or pembrolizumab plus chemotherapy.

根据 RECIST v1.1 标准，完全缓解/部分缓解或疾病稳定的参与者按1:1的比例随机分配至每3周一次的200毫克帕博利珠单抗加每日两次的300毫克奥拉帕利组，或帕博利珠单抗加化疗组。

Progression-free survival(PFS) and overall survival(OS) were primary endpoints.

无进展生存期（PFS）和总生存期（OS）是主要终点。

Results

Of 460 participants receiving induction treatment, 271 were randomly assigned to postinduction therapy.

在460名接受诱导治疗的参与者中，有271人被随机分配到诱导后治疗。

The median PFS was 5.5 months in the pembrolizumab plus olaparib group versus 5.6 months in the pembrolizumab plus chemotherapy group [hazard ratio(HR), 0.98; 95% confidence interval(CI), 0.72-1.33; P = 0.4556].

在帕博利珠单抗加奥拉帕利组的中位无进展生存期为5.5个月，而在帕博利珠单抗加化疗组为5.6个月[风险比(HR), 0.98; 95%置信区间(CI), 0.72-1.33; P = 0.4556]。

The median OS was 25.1 versus 23.4 months, respectively (HR, 0.95; 95% CI, 0.64-1.40).

中位总生存期分别为25.1个月和23.4个月（风险比，0.95；95%置信区间，0.64-1.40）。

In participants with tumor BRCA1/BRCA2 mutations (tBRCAm), HRs for PFS (HR, 0.70; 95% CI, 0.33-1.48) and OS (0.81; 95% CI, 0.28-2.37) favored pembrolizumab plus olaparib.

在携带肿瘤BRCA1/BRCA2突变（tBRCAm）的参与者中，无进展生存期（HR，0.70；95%置信区间，0.33-1.48）和总生存期（HR，0.81；95%置信区间，0.28-2.37）的风险比均倾向于支持帕博利珠单抗联合奥拉帕利治疗。

Treatment-related adverse events occurred in 84.4% and 96.2% of participants receiving pembrolizumab plus olaparib and pembrolizumab plus chemotherapy, respectively.

分别有84.4%和96.2%接受pembrolizumab联合olaparib和pembrolizumab联合化疗的参与者出现了治疗相关的不良事件。

Conclusions

Although the primary endpoint was not met, postinduction pembrolizumab plus olaparib therapy resulted in similar PFS and OS compared with pembrolizumab plus chemotherapy in this setting.

尽管主要终点未达到，但在这种情况下，诱导后pembrolizumab联合olaparib治疗与pembrolizumab联合化疗相比，无进展生存期（PFS）和总生存（OS）相似。

The positive trend for PFS and OS in participants with tBRCAm suggests a potential nonchemotherapy strategy for maintaining clinical benefit attained with first-line pembrolizumab plus chemotherapy induction treatment.

在 tBRCAm 突变的参与者中，无进展生存期（PFS）和总生存期（OS）的积极趋势表明，维持与一线帕博利珠单抗加化疗诱导治疗所获得的临床益处，可能不需要化疗策略。

No new safety signals were identified.

未发现新的安全信号。