Ichikawa Yasuko, Seki Nobuhiko, Honda Takeshi, Sakugawa Makoto, Hosokawa Shinobu, Bessho Akihiro, Agemi Yoko, Shimokawa Tsuneo, Otani Sakiko, Nakahara Yoshiro, Naoki Katsuhiko, Yomota Makiko, Hosomi Yukio, Takiguchi Yuichi, Tokito Takaaki, Ando Shuji, Okamoto Hiroaki
Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan.
Transl Cancer Res. 2023 Apr 28;12(4):873-886. doi: 10.21037/tcr-22-2144. Epub 2023 Mar 23.
Currently, only a few treatment options exist for performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC), whereas the carboplatin/nab-paclitaxel (CBDCA/nab-PTX) regimen is attracting attention as a standard of care for PS 0-1 patients because of its wide suitability and modest risk of peripheral neuropathy. However, the treatment dose and schedule should be optimized for PS 2 patients. Therefore, we planned a single-arm phase II study to characterize the efficacy and tolerability of our modified CBDCA/nab-PTX regimen for untreated PS 2 patients with advanced NSCLC.
Enrolled patients were treated with CBDCA (area under the curve 5 on day 1) plus nab-PTX (70 mg/m on days 1, 8, and 15) every 4 weeks for up to six cycles. The primary endpoint was the progression-free survival (PFS) rate at 6 months. As exploratory analyses, the reasons for PS 2 (disease burden versus comorbidities/indeterminant) and the Charlson Comorbidity Index (CCI) were evaluated as efficacy indicators.
This study was terminated early because of slow accrual. Seventeen patients [median age, 68 years (range, 50-73 years)] received a median of three cycles. The 6-month PFS rate, median PFS, and median overall survival were 20.8% [95% confidence interval (CI): 0-41.6], 3.0 months (95% CI: 1.7-4.3), and 9.5 months (95% CI: 5.0-14.0), respectively. Exploratory analyses suggested better overall survival in patients whose PS was not attributable to the disease burden (median, 9.5 7.2 months) or whose CCI was ≤3 (median, 15.5 7.2 months). Grade 3-4 adverse events occurred in 12 (71%) patients, and grade 5 pleural infection occurred in one (6%) patient. Meanwhile, only one (6%) patient each experienced grade 1 peripheral neuropathy and grade 2 interstitial pneumonitis.
No conclusion could be drawn from this study because of its early termination. However, our modified CBDCA/nab-PTX regimen might be useful for PS 2 patients who hesitate to use regimens other than nab-PTX, and particularly patients concerned about peripheral neuropathy or interstitial pneumonitis. The potential role of PS 2 and CCI as efficacy predictors for this regimen should be further examined.
目前，对于体能状态（PS）为2的晚期非小细胞肺癌（NSCLC）患者，治疗选择有限，而卡铂/白蛋白结合型紫杉醇（CBDCA/nab-PTX）方案因其广泛的适用性和较低的外周神经病变风险，作为PS 0-1患者的标准治疗方案受到关注。然而，对于PS 2患者，治疗剂量和方案应进行优化。因此，我们计划开展一项单臂II期研究，以评估改良的CBDCA/nab-PTX方案治疗未经治疗的PS 2晚期NSCLC患者的疗效和耐受性。
入组患者接受CBDCA（第1天曲线下面积为5）加nab-PTX（第1、8和15天70mg/m²），每4周一次，最多六个周期。主要终点是6个月时的无进展生存（PFS）率。作为探索性分析，将PS为2的原因（疾病负担与合并症/不确定因素）和Charlson合并症指数（CCI）作为疗效指标进行评估。
由于入组缓慢，本研究提前终止。17例患者[中位年龄68岁（范围50-73岁）]接受的中位周期数为3个。6个月PFS率、中位PFS和中位总生存期分别为20.8%[95%置信区间（CI）：0-41.6]、3.0个月（95%CI：1.7-4.3）和9.5个月（95%CI：5.0-14.0）。探索性分析表明，PS不归因于疾病负担的患者（中位生存期9.5对7.2个月）或CCI≤3的患者（中位生存期15.5对7.2个月）总生存期更好。12例（71%）患者发生3-4级不良事件，1例（6%）患者发生5级胸膜感染。同时，各有1例（6%）患者发生1级外周神经病变和2级间质性肺炎。
由于本研究提前终止，无法得出结论。然而，我们改良的CBDCA/nab-PTX方案可能对犹豫使用除nab-PTX以外方案的PS 2患者有用，尤其是担心外周神经病变或间质性肺炎的患者。PS 2和CCI作为该方案疗效预测指标的潜在作用应进一步研究。
