Osimertinib and Stereotactic Radiosurgery for Brain Metastases in EGFR-Mutated Lung Cancer: The STARLET Joint Analysis of OUTRUN and LUOSICNS Randomized Trials.

We conducted two randomized phase II trials, OUTRUN and LUOSICNS, to evaluate the efficacy and safety of upfront stereotactic radiosurgery (SRS) plus osimertinib versus osimertinib in this patient population.

我们进行了两项随机II期试验，OUTRUN和LUOSICNS，以评估一线立体定向放射外科（SRS）联合奥希替尼与单独使用奥希替尼在这一患者群体中的疗效和安全性。

Methods

Participants with up to ten BM amenable to SRS were randomized 1:1 to SRS followed by osimertinib (80 mg daily) or osimertinib monotherapy.

最多有十个脑转移病灶的参与者被随机分为1:1，接受立体定向放射治疗(SRS)后服用奥希替尼(每日80毫克)或仅接受奥希替尼单药治疗。

SRS was delivered as a single or multi-fraction regimen.

立体定向放射治疗(SRS)以单次或多次分割方案进行。

The primary end point was 12-month intracranial progression-free survival(ic-PFS).

主要终点是12个月的颅内无进展生存期(ic-PFS)。

Key secondary end points include overall survival(OS), patterns of intracranial progression, and safety.

关键次要终点包括总生存(OS)、颅内进展模式和安全性。

Data from both trials were prospectively pooled for a joint analysis.

两项试验的数据已前瞻性地合并，用于联合分析。

Results

Overall, 79 participants were randomized.

总体而言，共有79名参与者被随机分配。

At a median follow-up of 39.0 months, 12-month ic-PFS was not significantly different between SRS plus osimertinib (n = 39) than osimertinib monotherapy (n = 40) (11%, 95% CI: -10% to 32%, p = 0.31; median ic-PFS 21.9 mo versus 17.2 mo).

在中位随访39.0个月时，立体定向放射外科(SRS)联合奥希替尼(n = 39)与奥希替尼单药治疗(n = 40)的12个月无进展生存期(ic-PFS)没有显著差异（11%，95%置信区间：-10%至32%，p = 0.31；中位ic-PFS为21.9个月对比17.2个月）。

Median OS was 46.1 versus 29.1 months.

总生存期(OS)的中位数分别为46.1个月和29.1个月。

Among those with intracranial progression, 35% in the SRS plus osimertinib group and 57% in the osimertinib monotherapy group underwent SRS at progression.

在发生颅内进展的患者中，接受立体定向放射外科（SRS）联合奥希替尼治疗的患者中有35%，而仅接受奥希替尼单药治疗的患者中有57%在进展时接受了SRS治疗。

Grade 3/4 radionecrosis occurred in 5% of participants treated with SRS plus osimertinib.

在接受SRS联合奥希替尼治疗的参与者中，有5%发生了3级/4级放射性坏死。

Conclusions

Adding upfront SRS to osimertinib did not significantly improve 12-month ic-PFS in EGFR-mutant NSCLC with BM.

在伴有脑转移的EGFR突变型非小细胞肺癌中，将SRS作为一线治疗加入到奥希替尼治疗中，并未显著改善12个月的颅内无进展生存期。

This represents the first randomized evidence supporting the use of osimertinib monotherapy as upfront therapy in minimally symptomatic patients with low-burden BM.

这代表了首个随机证据，支持将奥希替尼单药治疗作为伴有低负担脑转移且症状轻微患者的首选一线治疗。

gov_identifier

OUTRUN: NCT03497767; LUOSICNS: NCT03769103.

OUTRUN: NCT03497767; LUOSICNS: NCT03769103.