Abstract：
Systemic treatment options for NSCLC with brain metastases (BMs) are scarce. We evaluated the activity and safety of camrelizumab plus chemotherapy as first-line therapy in patients with advanced nonsquamous NSCLC with BMs.
This was a multicenter, single-arm, phase 2 trial (NCT04211090) conducted at seven hospitals in China. Eligible patients had treatment-naive metastatic nonsquamous NSCLC and BMs that were asymptomatic or symptoms controlled with dehydration therapy and no previous systemic treatment or local therapy for the target brain lesion. Patients received camrelizumab (200 mg) plus pemetrexed (500 mg/m2) and carboplatin (area under the curve 5) intravenously on day 1 of each 21-day cycle for four cycles, followed by maintenance with camrelizumab (200 mg) and pemetrexed (500 mg/m2) every 21 days until disease progression, unacceptable toxicity, or death. The primary end point was confirmed intracranial objective response rate according to modified Response Evaluation Criteria in Solid Tumors version 1.1, which was primarily analyzed in the efficacy analysis set (EAS).
A total of 45 patients were enrolled and treated (full analysis set), with 40 patients having at least one post-baseline tumor assessment (EAS). As of August 30, 2022, median follow-up duration was 12.5 months (95% confidence interval [CI]: 9.2-17.3). The confirmed intracranial objective response rate was 52.5% (95% CI: 36.1-68.5) in EAS and 46.7% (95% CI: 31.7-62.1) in full analysis set. The extracranial objective response rate was 47.5% (95% CI: 31.5-63.9) and 42.2% (95% CI: 27.7-57.8), respectively. Median intracranial progression-free survival was 7.6 months (95% CI: 4.6-not reached [NR]), median overall progression-free survival was 7.4 months (95% CI: 4.4-NR), and median overall survival was 21.0 months (95% CI: 15.9-NR). The most common treatment-related adverse events of grade 3 or higher were neutrophil count decrease (six [13.3%]) and anemia (four [8.9%]). One treatment-related death occurred owing to immune-related pneumonia. Linear mixed-effects model displayed that a positive trend for improvement in cognitive function and quality of life was observed based on Montreal Cognitive Assessment and Functional Assessment of Cancer Therapy-Lung scores (p = 0.025, p < 0.001).
Camrelizumab plus pemetrexed and carboplatin was found to have an activity with manageable toxicity and to improve cognitive function and quality of life for patients with nonsquamous NSCLC with BMs in the first-line setting.
This was a multicenter, single-arm, phase 2 trial (NCT04211090) conducted at seven hospitals in China. Eligible patients had treatment-naive metastatic nonsquamous NSCLC and BMs that were asymptomatic or symptoms controlled with dehydration therapy and no previous systemic treatment or local therapy for the target brain lesion. Patients received camrelizumab (200 mg) plus pemetrexed (500 mg/m2) and carboplatin (area under the curve 5) intravenously on day 1 of each 21-day cycle for four cycles, followed by maintenance with camrelizumab (200 mg) and pemetrexed (500 mg/m2) every 21 days until disease progression, unacceptable toxicity, or death. The primary end point was confirmed intracranial objective response rate according to modified Response Evaluation Criteria in Solid Tumors version 1.1, which was primarily analyzed in the efficacy analysis set (EAS).
A total of 45 patients were enrolled and treated (full analysis set), with 40 patients having at least one post-baseline tumor assessment (EAS). As of August 30, 2022, median follow-up duration was 12.5 months (95% confidence interval [CI]: 9.2-17.3). The confirmed intracranial objective response rate was 52.5% (95% CI: 36.1-68.5) in EAS and 46.7% (95% CI: 31.7-62.1) in full analysis set. The extracranial objective response rate was 47.5% (95% CI: 31.5-63.9) and 42.2% (95% CI: 27.7-57.8), respectively. Median intracranial progression-free survival was 7.6 months (95% CI: 4.6-not reached [NR]), median overall progression-free survival was 7.4 months (95% CI: 4.4-NR), and median overall survival was 21.0 months (95% CI: 15.9-NR). The most common treatment-related adverse events of grade 3 or higher were neutrophil count decrease (six [13.3%]) and anemia (four [8.9%]). One treatment-related death occurred owing to immune-related pneumonia. Linear mixed-effects model displayed that a positive trend for improvement in cognitive function and quality of life was observed based on Montreal Cognitive Assessment and Functional Assessment of Cancer Therapy-Lung scores (p = 0.025, p < 0.001).
Camrelizumab plus pemetrexed and carboplatin was found to have an activity with manageable toxicity and to improve cognitive function and quality of life for patients with nonsquamous NSCLC with BMs in the first-line setting.
摘要：
背景：非小细胞肺癌（NSCLC）伴脑转移（BMs）的系统治疗方案很少。我们评估了卡姆瑞珠单抗联合化疗作为晚期非鳞状细胞肺癌患者BMs的一线治疗的活性和安全性。
方法：这是一个多中心，单臂,2期试验（NCT04211090）在中国7家医院进行。符合条件的患者为未治疗的转移性非鳞状NSCLC和无症状或脱水治疗控制症状的BMs。以前没有针对目标脑部病变的全身治疗或局部治疗。患者在每个21天周期的第1天静脉注射卡利珠单抗（200mg）加培美曲塞（500mg/m2）和卡铂（曲线5下面积），共四个周期。随后每21天使用卡利珠单抗（200mg）和培美曲塞（500mg/m2）维持治疗，直至疾病进展，不可接受的毒性或死亡。主要终点是根据实体瘤1.1版中修改的反应评估标准确认的颅内客观反应率（iORR），该标准主要在疗效分析集（EAS）中进行分析。
结果：纳入45例患者并接受治疗（完整分析集[FAS]），40名患者至少进行了一次基线后肿瘤评估（EAS）。截至2022年8月30日，中位随访时间为12.5个月（95%CI9.2-17.3）。确认的iORR在EAS中为52.5%（95%CI36.1-68.5），在FAS中为46.7%（95%CI31.7-62.1）。颅外ORR为47.5%（95%CI31.5-63.9）和42.2%（95%CI27.7-57.8），分别。中位颅内无进展生存期（iPFS）为7.6个月（95%CI4.6-未达到[NR]），中位总PFS为7.4个月(95%CI4.4-NR),中位总生存期为21.0个月(95%CI15.9-NR).最常见的3级或更高的治疗相关不良事件是中性粒细胞计数减少（6[13.3%]）和贫血（4[8.9%]）。1例治疗相关死亡是由于免疫相关肺炎。线性混合效应模型显示，根据蒙特利尔认知评估和癌症治疗肺功能评估评分观察到认知功能和生活质量改善的积极趋势（P=0.025，P<0.001）。
结论：卡利珠单抗联合培美曲塞和卡铂显示出毒性可控的活性，在一线治疗中，非鳞状细胞肺癌患者的认知功能和生活质量得到改善。
方法：这是一个多中心，单臂,2期试验（NCT04211090）在中国7家医院进行。符合条件的患者为未治疗的转移性非鳞状NSCLC和无症状或脱水治疗控制症状的BMs。以前没有针对目标脑部病变的全身治疗或局部治疗。患者在每个21天周期的第1天静脉注射卡利珠单抗（200mg）加培美曲塞（500mg/m2）和卡铂（曲线5下面积），共四个周期。随后每21天使用卡利珠单抗（200mg）和培美曲塞（500mg/m2）维持治疗，直至疾病进展，不可接受的毒性或死亡。主要终点是根据实体瘤1.1版中修改的反应评估标准确认的颅内客观反应率（iORR），该标准主要在疗效分析集（EAS）中进行分析。
结果：纳入45例患者并接受治疗（完整分析集[FAS]），40名患者至少进行了一次基线后肿瘤评估（EAS）。截至2022年8月30日，中位随访时间为12.5个月（95%CI9.2-17.3）。确认的iORR在EAS中为52.5%（95%CI36.1-68.5），在FAS中为46.7%（95%CI31.7-62.1）。颅外ORR为47.5%（95%CI31.5-63.9）和42.2%（95%CI27.7-57.8），分别。中位颅内无进展生存期（iPFS）为7.6个月（95%CI4.6-未达到[NR]），中位总PFS为7.4个月(95%CI4.4-NR),中位总生存期为21.0个月(95%CI15.9-NR).最常见的3级或更高的治疗相关不良事件是中性粒细胞计数减少（6[13.3%]）和贫血（4[8.9%]）。1例治疗相关死亡是由于免疫相关肺炎。线性混合效应模型显示，根据蒙特利尔认知评估和癌症治疗肺功能评估评分观察到认知功能和生活质量改善的积极趋势（P=0.025，P<0.001）。
结论：卡利珠单抗联合培美曲塞和卡铂显示出毒性可控的活性，在一线治疗中，非鳞状细胞肺癌患者的认知功能和生活质量得到改善。
