倘若肿瘤有远处转移，或肿瘤虽位于胸腔，但其分布超出一個放射治疗野，则称为广泛期。
除了活检以明确诊断外，病人应该作以下的检查： 1）PET-CT； 2）脑的核磁共振。
病人应给予化疗。治疗结束后同样要做CT和脑核磁共振。要是完全缓解，也应给予预防性脑放疗。常用的化疗为顺铂和依托泊甙（Etoposide，VP-16）。要是一般状况较差，可以用卡铂和依托泊甙。
第一线Pembrolizumab加标准化疗可改善广泛期小细胞肺癌的无进展生存率 (8/2/2020)
First line pembrolizumab plus standard chemotherapy improves progression-free survival in small cell lung cancer
SCLC约占所有肺癌的15％，5年总生存率约为6％至7％。用于广泛期小细胞肺癌的标准一线治疗在过去30年中一直是铂类/依托泊苷, 但该方案的中位总生存期不到1年。
KEYNOTE-604临床试验在18个国家/地区的133个地点进行了研究，并以1:1的比例将453例先前未接受过治疗的广泛期小细胞肺癌患者随机分配给pembrolizumab/铂类/依托泊苷或安慰剂/铂类/依托泊苷。每3周一次给予pembrolizumab 200 毫克（一个周期），最多35个周期，外加4个周期的铂类/依托泊苷。在对照组中，以相同的化疗方案给予生理盐水安慰剂。研究者选择铂类为顺铂或卡铂。入组时允许治疗和病情稳定的脑转移瘤。
基线特征在两个治疗组之间达到了很好的平衡，但在pembrolizumab组中有更多的脑转移（14.5％比9.8％）。研究患者的中位年龄为65岁。大约40％的患者肝转移。41％的人检测PD-L1阳性（综合阳性评分≥1％）。
Pembrolizumab组的客观响应率为70.6％，而安慰剂/依托泊苷/铂的客观响应率为61.8％。在12个月时，观察到的持续响应分别为19％和3％。
在第二次中期分析中，pembrolizumab组的无进展生存期显着延长（HR= 0.75； P = .0023）。 12个月无进展生存率分别为13.6％和3.1％。最终分析时，pembrolizumab组有169例患者死亡，对照组为188例。总体生存的危险比为0.80（95％置信区间= 0.64-0.98； P = .0164）。估计的24个月总生存率分别为22.5％和11.2％。对于无进展生存期和总生存期的亚组分析，无论PD-L1阳性如何，结果都是相似的。至今为止，pembrolizumab组有20例患者接受治疗，而安慰剂组有3例正在接受治疗。疾病进展是停药的最常见原因。
两组中约75％的患者经历了3或4级不良事件。 Pembrolizumab组中有14.8％的患者因不良事件而终止治疗，而对照组中则有6.3％。 两组的不良事件很相似。 导致死亡的不良事件发生率分别为6.3％和5.4％。 两组由于治疗引起的死亡率相同（2.7％）。与先前的研究一致，pembrolizumab组中约25％的患者有免疫治疗相关的不良事件。 但是，没有患者死于免疫相关事件, 而且大多数事件是1/2级。
Small cell lung cancer (SCLC) accounts for about 15% of all lung cancers, and the 5-year overall survival rate is about 6% to 7%. The standard first-line treatment for extensive-stage SCLC has been platinum/etoposide for the past 30 years, but the median overall survival of this regimen is less than 1 year.
The KEYNOTE-604 clinical trial was conducted in 133 sites in 18 countries/regions, and 453 patients with previously untreated extensive-stage SCLC were randomly assigned at a ratio of 1:1 to pembrolizumab/platinum/etoposide or placebo/platinum/etoposide. Patients were given pembrolizumab 200 mg (one cycle) every 3 weeks for a maximum of 35 cycles, plus 4 cycles of platinum/etoposide at front. In the control group, normal saline placebo was given with the same chemotherapy regimen. The researchers chose either cisplatin or carboplatin as platinum. At the time of enrollment, previously treated and stable brain metastases were allowed.
The baseline characteristics were well-balanced between the two treatment groups, but there were more brain metastases in the pembrolizumab group (14.5% vs. 9.8%). The median age of the study patients was 65 years. About 40% of patients had liver metastases. 41% tested positive for PD-L1 (combined positive score ≥ 1%).
The objective response rate of the pembrolizumab group was 70.6%, while that of placebo/etoposide/platinum was 61.8%. At 12 months, the observed sustained response was 19% and 3%, respectively.
In the second interim analysis, the progression-free survival of the pembrolizumab group was significantly prolonged (HR = 0.75; P = .0023). The 12-month progression-free survival rates were 13.6% and 3.1%, respectively. In the final analysis, 169 patients died in the pembrolizumab group and 188 patients in the control group. The hazard ratio for overall survival was 0.80 (95% confidence interval = 0.64-0.98; P = .0164). The estimated 24-month overall survival rates were 22.5% and 11.2%, respectively. For subgroup analysis of progression-free survival and overall survival, the results were similar regardless of PD-L1 positive. So far, 20 patients in the pembrolizumab group are receiving treatment, while 3 patients in the placebo group are receiving treatment. Disease progression is the most common reason for discontinuation.
Approximately 75% of patients in both groups experienced grade 3 or 4 adverse events. A total of 14.8% of patients in the pembrolizumab group discontinued treatment due to adverse events, compared with 6.3% in the control group. The adverse events of the two groups were very similar. The incidence of adverse events leading to death was 6.3% and 5.4%, respectively. The two groups had the same mortality due to treatment (2.7%). Consistent with previous studies, approximately 25% of patients in the pembrolizumab group had immunotherapy-related adverse events. However, no patient died from immune-related events, and most events were grade 1 or 2.
参考文献 Reference Rudin CM et al. ASCO20 Virtual Scientific Program. Abstract 9001 Rudin CM et al. J Clin Oncol. May 29, 2020