Lara Primo N, Moon James, Redman Mary W, Semrad Thomas J, Kelly Karen, Allen Jeffrey W, Gitlitz Barbara J, Mack Philip C, Gandara David R
*University of California Davis Comprehensive Cancer Center, Sacramento, California; †SWOG Statistical Center and the Fred Hutchinson Cancer Research Center, Seattle, Washington; ‡Humboldt Medical Specialists, Eureka, California; and §Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
J Thorac Oncol. 2015 Jan;10(1):110-5. doi: 10.1097/JTO.0000000000000385.
Extensive-stage small-cell lung cancer (SCLC) patients who progress after platinum-based chemotherapy are traditionally categorized as platinum sensitive (progression ≥ 90 days from last platinum dose) or refractory (progression < 90 days), a practice arising from seminal observations of worse survival in refractory patients. Subsequent trials accounted for platinum sensitivity, resulting in higher sample sizes and increased resource use.
To assess whether platinum-sensitivity status remains associated with outcomes, patient-level data from recent Southwest Oncology Group trials in second- and/or third-line extensive-stage SCLC were pooled. Hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) accounting for platinum sensitivity were calculated using unadjusted and adjusted Cox Proportional Hazard models. Recursive partitioning was performed to define prognostic risk groups.
Of 329 patients, 151 were platinum sensitive and 178 refractory. HRs from unadjusted Cox PFS and OS models for refractory versus sensitive disease were 1.0 (95% confidence interval, 0.81-1.25; p = 0.98) and 1.24 (0.99-1.57; p = 0.06), respectively. Adjusted Cox models showed that only elevated serum lactate dehydrogenase (HR, 2.04; p < 0.001), males (HR, 1.36; p = 0.04), performance status of 1 (HR, 1.25; p = 0.02), and weight loss greater than or equal to 5% (1.53, p = 0.01) were independently associated with OS. Platinum-sensitivity status was not associated with PFS (HR, 1.11; p = 0.49) or OS (HR, 1.25; p = 0.14), except in a model that excluded 36 patients who received more than one prior chemotherapy regimen (HR, 1.34; p = 0.049). Prognostic groups with differential OS outcomes (high, intermediate, and poor risk) were identified.
Platinum-sensitivity status may no longer be strongly associated with PFS or OS in at least one multivariate model. Validation of prognostic risk groups identified here is warranted. These data have critical implications in the design of future SCLC trials.
广泛期小细胞肺癌（SCLC）患者在铂类化疗后病情进展，传统上分为铂敏感型（自最后一剂铂给药后进展≥90天）或难治型（进展<90天），这种分类源于对难治型患者较差生存率的开创性观察。随后的试验考虑了铂敏感性，导致样本量增加和资源使用增多。
为评估铂敏感性状态是否仍与预后相关，汇总了西南肿瘤协作组最近在二线和/或三线广泛期SCLC试验中的患者水平数据。使用未调整和调整后的Cox比例风险模型计算考虑铂敏感性的无进展生存期（PFS）和总生存期（OS）的风险比（HR）。进行递归划分以定义预后风险组。
329例患者中，151例为铂敏感型，178例为难治型。未调整的Cox PFS和OS模型中，难治型与敏感型疾病的HR分别为1.0（95%置信区间，0.81 - 1.25；p = 0.98）和1.24（0.99 - 1.57；p = 0.06）。调整后的Cox模型显示，只有血清乳酸脱氢酶升高（HR，2.04；p < 0.001）、男性（HR，1.36；p = 0.04）、体力状况为1（HR，1.25；p = 0.02）以及体重减轻≥5%（1.53，p = 0.01）与OS独立相关。铂敏感性状态与PFS（HR，1.11；p = 0.49）或OS（HR，1.25；p = 0.14）无关，除非在排除36例接受过一种以上既往化疗方案的患者的模型中（HR，1.34；p = 0.049）。确定了具有不同OS结果的预后组（高、中、低风险）。
在至少一个多变量模型中，铂敏感性状态可能不再与PFS或OS密切相关。有必要对此处确定的预后风险组进行验证。这些数据对未来SCLC试验的设计具有关键意义。
