Bevacizumab plus nab-paclitaxel and platinum as second-line therapy for driver-gene-negative non-squamous non-small cell lung cancer after immunochemotherapy: A prospective single-arm single-centre study

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.

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.

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.

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.