Zhang, Chan-Yuan, Sun, Hao, Su, Jun-Wei, Chen, Yu-Qing, Zhang, Shi-Ling, Zheng, Ming-Ying, Li, Yu-Fa, Huang, Jie, Zhang, Chao, Tai, Zai-Xian, Cai, Miao, Zhang, Xu-Chao, Su, Jian, Xu, Chong-Rui, Yan, Hong-Hong, Chen, Hua-Jun, Wu, Yi-Long, and Yang, Jin-Ji
• The ORR of ABCP/ECT for T -SCLC exceeds 70 %, with a mPFS of 5.1 m. • PD-L1 inhibitor-based combination therapy significantly prolonged pOS of T -SCLC. • Combination immunotherapy could serve as a potential treatment option for T -SCLC. • Upregulation of SFTPA1, EGFR L858R, or PD-L1 ≥ 1 % may benefit these patients. 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. [ABSTRACT FROM AUTHOR]