Ying Lin, Yunbo Yu, Zhihuang Hu, Chenchen Wei, Zezhou Wang, Yao Zhang, Zhenhua Wu, Bo Yu, Xinmin Zhao, Hui Yu, Xianghua Wu, Huijie Wang, Jialei Wang
The BAP regimen demonstrated preliminary efficacy with manageable safety as a second-line therapy for patients with advanced driver-gene-negative nsqNSCLC after immunochemotherapy. Plasma TWEAK levels may serve as a potential biomarker to help identify patients who might benefit most from this sequential treatment modality, pending further independent validation. Further studies are needed.
BACKGROUND: Effective second-line therapy is urgently needed for patients with driver-gene-negative non-squamous non-small cell lung cancer (nsqNSCLC) who progress after first-line immunochemotherapy. This study aims to evaluate the efficacy and safety of bevacizumab combined with nab-paclitaxel and platinum (the BAP regimen) in this setting.
METHODS: This prospective, single-arm, single-centre study enrolled 56 patients with advanced driver-gene-negative nsqNSCLC failing first-line immunochemotherapy. Patients received bevacizumab, nab-paclitaxel, and platinum (carboplatin or cisplatin) for 4-6 cycles, followed by bevacizumab maintenance. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety.
RESULTS: All patients had failed first-line platinum-based immunochemotherapy. The confirmed ORR was 46.4% (26/56, 95% confidence interval [CI]: 34.0%-59.3%, p < 0.001), and DCR was 75%. The median PFS and OS were 5.6 (95% CI: 4.35-6.79) and 18.8 (95% CI: 10.31-27.24) months. Patients with ≤ 2 metastatic organs had a significantly longer median PFS than those with >2 metastatic organs (p = 0.014). Multivariable Cox analysis showed that a platinum-free interval <6 months was an independent biomarker of worse PFS. The safety profile was manageable. Plasma proteomics identified baseline high TWEAK level as a potential biomarker for response to both the second-line BAP regimen and first-line immunochemotherapy. Patients with high baseline TWEAK levels before first-line immunochemotherapy showed a median OS of 39.8 months under this sequential treatment modality.
CONCLUSIONS: The BAP regimen demonstrated preliminary efficacy with manageable safety as a second-line therapy for patients with advanced driver-gene-negative nsqNSCLC after immunochemotherapy. Plasma TWEAK levels may serve as a potential biomarker to help identify patients who might benefit most from this sequential treatment modality, pending further independent validation. Further studies are needed.