Efficacy of PD-(L)1 inhibitors plus anlotinib in the second-line treatment of extensive-stage small cell lung cancer
Abstract Background The efficacy of second-line therapy for extensive-stage small cell lung cancer (ES-SCLC) is still limited, with the PFS of 2–3 months. Given the synergistic effect of PD-(L)1 inhibitors and anti-angiogenic agents, their combination represents a novel and promising strategy to rep...
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BMC
2025-07-01
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| Online Access: | https://doi.org/10.1186/s12885-025-14458-5 |
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| author | Jian Zhang Zijie Wu Shuyun Wang Yanxin Sun Jiake Wu Dahai Wang Yihui Ge Juan Li Haifeng Sun Qinglei Cheng Aiqin Gao Yuping Sun |
| author_facet | Jian Zhang Zijie Wu Shuyun Wang Yanxin Sun Jiake Wu Dahai Wang Yihui Ge Juan Li Haifeng Sun Qinglei Cheng Aiqin Gao Yuping Sun |
| author_sort | Jian Zhang |
| collection | DOAJ |
| description | Abstract Background The efficacy of second-line therapy for extensive-stage small cell lung cancer (ES-SCLC) is still limited, with the PFS of 2–3 months. Given the synergistic effect of PD-(L)1 inhibitors and anti-angiogenic agents, their combination represents a novel and promising strategy to reprogram the protumoral microenvironment and improve patient outcome. However, the efficacy of PD-(L)1 inhibitors plus anlotinib as the second-line treatment of ES-SCLC is undetermined in the real world. Methods We retrospectively analyzed 389 ES-SCLC patients from 3 cancer centers. All the patients received one of the following second-line schemes: PD-(L)1 inhibitors plus anlotinib (I + A), PD-(L)1 inhibitors plus chemotherapy (I + C), or chemotherapy alone (C). The efficacy, including the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety were compared among the three groups. We also analyzed the impact of first-line immune checkpoint inhibitors (ICIs) on the efficacy of second-line I + A. Results The baseline clinical characteristics among three groups were largely balanced. I + A treatment demonstrated significantly higher ORR (30.2%) and DCR (82.6%) compared with I + C (ORR = 17.6%, DCR = 68.8%) and C (ORR = 18.0%, DCR = 53.9%). Furthermore, I + A group showed the longest mPFS (7.2 months) and mOS (33.5 months), compared to I + C (mPFS = 4.6 months, mOS = 19.0 months, both P < 0.001) and C (mPFS = 3.4 months, P < 0.01; mOS = 18.3 months, P = 0.083). The benefit of I + A treatment persists independent of the administration of first-line ICIs. A stratified analysis revealed that female patients and those with oligometastasis (≤ 3 metastatic sites) benefit more from I + A treatment than male patients and those with polymetastasis. In terms of safety, I + A group displayed the lowest incidence of ≥ grade 3 myelosuppression compared to the I + C and C groups (3.5% vs. 11.2% vs. 16.3%, P < 0.01). However, I + A treatment was associated with a higher prevalence of immune-related pneumonia (2.3% vs. 0% vs. 0%, P < 0.05) and hemoptysis (1.4% vs. 0% vs. 0.6%, P < 0.05) compared to I + C and C treatment. Conclusions PD-(L)1 inhibitors and anlotinib has promising efficacy and manageable toxicity as the second-line therapy of ES-SCLC. |
| format | Article |
| id | doaj-art-1e64966de4b64567a67e97bb44bc32e8 |
| institution | DOAJ |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-1e64966de4b64567a67e97bb44bc32e82025-08-20T03:03:44ZengBMCBMC Cancer1471-24072025-07-012511910.1186/s12885-025-14458-5Efficacy of PD-(L)1 inhibitors plus anlotinib in the second-line treatment of extensive-stage small cell lung cancerJian Zhang0Zijie Wu1Shuyun Wang2Yanxin Sun3Jiake Wu4Dahai Wang5Yihui Ge6Juan Li7Haifeng Sun8Qinglei Cheng9Aiqin Gao10Yuping Sun11Phase I Clinical Research Center, Shandong Cancer Hospital and Institute, Zhangqiu District People’s Hospital, Shandong First Medical University, Shandong Academy of Medical SciencesPhase I Clinical Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesPhase I Clinical Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesSchool of Clinical Medicine, Weifang Medical UniversityPhase I Clinical Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesPhase I Clinical Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesPhase I Clinical Research Center, Shandong University Cancer CenterPhase I Clinical Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesSchool of Clinical Medicine, Weifang Medical UniversityPhase I Clinical Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesDepartment of Thoracic Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesPhase I Clinical Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesAbstract Background The efficacy of second-line therapy for extensive-stage small cell lung cancer (ES-SCLC) is still limited, with the PFS of 2–3 months. Given the synergistic effect of PD-(L)1 inhibitors and anti-angiogenic agents, their combination represents a novel and promising strategy to reprogram the protumoral microenvironment and improve patient outcome. However, the efficacy of PD-(L)1 inhibitors plus anlotinib as the second-line treatment of ES-SCLC is undetermined in the real world. Methods We retrospectively analyzed 389 ES-SCLC patients from 3 cancer centers. All the patients received one of the following second-line schemes: PD-(L)1 inhibitors plus anlotinib (I + A), PD-(L)1 inhibitors plus chemotherapy (I + C), or chemotherapy alone (C). The efficacy, including the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety were compared among the three groups. We also analyzed the impact of first-line immune checkpoint inhibitors (ICIs) on the efficacy of second-line I + A. Results The baseline clinical characteristics among three groups were largely balanced. I + A treatment demonstrated significantly higher ORR (30.2%) and DCR (82.6%) compared with I + C (ORR = 17.6%, DCR = 68.8%) and C (ORR = 18.0%, DCR = 53.9%). Furthermore, I + A group showed the longest mPFS (7.2 months) and mOS (33.5 months), compared to I + C (mPFS = 4.6 months, mOS = 19.0 months, both P < 0.001) and C (mPFS = 3.4 months, P < 0.01; mOS = 18.3 months, P = 0.083). The benefit of I + A treatment persists independent of the administration of first-line ICIs. A stratified analysis revealed that female patients and those with oligometastasis (≤ 3 metastatic sites) benefit more from I + A treatment than male patients and those with polymetastasis. In terms of safety, I + A group displayed the lowest incidence of ≥ grade 3 myelosuppression compared to the I + C and C groups (3.5% vs. 11.2% vs. 16.3%, P < 0.01). However, I + A treatment was associated with a higher prevalence of immune-related pneumonia (2.3% vs. 0% vs. 0%, P < 0.05) and hemoptysis (1.4% vs. 0% vs. 0.6%, P < 0.05) compared to I + C and C treatment. Conclusions PD-(L)1 inhibitors and anlotinib has promising efficacy and manageable toxicity as the second-line therapy of ES-SCLC.https://doi.org/10.1186/s12885-025-14458-5Extensive-stage small cell lung cancer (ES-SCLC)PD-(L)1 inhibitorsAnlotinibEfficacySafety |
| spellingShingle | Jian Zhang Zijie Wu Shuyun Wang Yanxin Sun Jiake Wu Dahai Wang Yihui Ge Juan Li Haifeng Sun Qinglei Cheng Aiqin Gao Yuping Sun Efficacy of PD-(L)1 inhibitors plus anlotinib in the second-line treatment of extensive-stage small cell lung cancer BMC Cancer Extensive-stage small cell lung cancer (ES-SCLC) PD-(L)1 inhibitors Anlotinib Efficacy Safety |
| title | Efficacy of PD-(L)1 inhibitors plus anlotinib in the second-line treatment of extensive-stage small cell lung cancer |
| title_full | Efficacy of PD-(L)1 inhibitors plus anlotinib in the second-line treatment of extensive-stage small cell lung cancer |
| title_fullStr | Efficacy of PD-(L)1 inhibitors plus anlotinib in the second-line treatment of extensive-stage small cell lung cancer |
| title_full_unstemmed | Efficacy of PD-(L)1 inhibitors plus anlotinib in the second-line treatment of extensive-stage small cell lung cancer |
| title_short | Efficacy of PD-(L)1 inhibitors plus anlotinib in the second-line treatment of extensive-stage small cell lung cancer |
| title_sort | efficacy of pd l 1 inhibitors plus anlotinib in the second line treatment of extensive stage small cell lung cancer |
| topic | Extensive-stage small cell lung cancer (ES-SCLC) PD-(L)1 inhibitors Anlotinib Efficacy Safety |
| url | https://doi.org/10.1186/s12885-025-14458-5 |
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