The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China; Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Lung Cancer. 2023 Jan;175:68-78. doi: 10.1016/j.lungcan.2022.11.016. Epub 2022 Nov 25.
Transformed small-cell lung cancer (T-SCLC) has an extremely poor prognosis, and no remedies based on immunotherapy have been evaluated among T-SCLC patients. We retrospectively analysed the efficacy and safety of combining atezolizumab with chemotherapy for T-SCLC.
Forty-seven patients harbouring EGFR mutations who developed T-SCLC were enrolled. Eleven patients who used immunotherapy were defined as the I/O group, and the remaining 36 were defined as the Non-I/O group. Clinical characteristics, pathological data, and survival outcomes were collected. RNA sequencing and whole-exome sequencing (WES) were performed for in-depth analysis.
All patients received at least one line of EGFR-TKI before rebiopsy to confirm T-SCLC. Nine patients received atezolizumab-bevacizumab-carboplatin-paclitaxel (albumin-bound) (ABCP), and the remaining 2 received atezolizumab-etoposide-carboplatin (ECT) in the I/O group. The objective response rate was 73 % (8/11). The median progression-free survival (mPFS) of T-SCLC on post-transformation therapy with I/O group and Non-I/O group was 5.1 m and 4.1 m, respectively. The median post-T-SCLC overall survival of the I/O group was significantly longer than that Non-I/O group (20.2 m vs 7.9 m, P ＜ 0.01). T-SCLC harbouring EGFR L858R tended to be longer than EGFR 19del (mPFS: not reached vs 3.7 m, P = 0.11). Positive PD-L1 status was also associated with PFS benefits (mPFS: 6.0 m vs 3.7 m, P = 0.20). Furthermore, RNA sequencing revealed that expression of SFTPA1 is significantly higher in the durable clinical benefit group. WES showed that STC2 mutation is more frequently observed at the time-point immunotherapy acquired resistance. Combination therapy based on a PD-L1 inhibitor was well tolerated, and the safety profile was consistent with previously reported studies.
Our study first demonstrated that a PD-L1 inhibitor combined with chemotherapy ± bevacizumab could be a potential safe option for specific SCLC-transformed patients. Subsequent studies with more patients are essential to verify the efficacy and potential biomarkers.
转化型小细胞肺癌（T-SCLC）预后极差，尚未评估免疫疗法在 T-SCLC 患者中的疗效。本研究回顾性分析了阿替利珠单抗联合化疗治疗 T-SCLC 的疗效和安全性。
纳入 47 例携带 EGFR 突变且发生 T-SCLC 的患者。将使用免疫治疗的 11 例患者定义为 I/O 组，其余 36 例定义为非 I/O 组。收集临床特征、病理数据和生存结局。对所有患者进行 RNA 测序和全外显子组测序（WES）进行深入分析。
所有患者均在重新活检以确认 T-SCLC 之前至少接受过一线 EGFR-TKI 治疗。9 例患者接受了阿替利珠单抗联合贝伐珠单抗联合卡铂紫杉醇（白蛋白结合型）（ABCP）治疗，其余 2 例接受了阿替利珠单抗联合依托泊苷联合卡铂（ECT）治疗。I/O 组客观缓解率为 73%（8/11）。T-SCLC 患者在接受 I/O 组和非 I/O 组治疗后的无进展生存期（mPFS）分别为 5.1 个月和 4.1 个月。I/O 组患者的 T-SCLC 总生存期明显长于非 I/O 组（20.2 个月比 7.9 个月，P＜0.01）。T-SCLC 患者携带 EGFR L858R 比携带 EGFR 19del 的患者的 mPFS 更长（mPFS：未达到比 3.7 个月，P=0.11）。PD-L1 阳性状态也与 PFS 获益相关（mPFS：6.0 个月比 3.7 个月，P=0.20）。此外，RNA 测序显示，在具有持久临床获益的患者中，SFTPA1 的表达显著升高。WES 显示，STC2 突变在免疫治疗获得耐药时更频繁发生。基于 PD-L1 抑制剂的联合治疗耐受性良好，安全性与先前报道的研究一致。
本研究首次证明，PD-L1 抑制剂联合化疗±贝伐珠单抗可能是特定 SCLC 转化患者的一种潜在安全选择。需要更多患者的后续研究来验证疗效和潜在的生物标志物。
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