Abstract
At present, treatment options for osimertinib resistance are very limited. Dual inhibition of the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) significantly improved the progression-free survival (PFS) of advanced EGFR-mutant non–small cell lung cancer (NSCLC). After EGFR-tyrosine kinase inhibitor (TKI) resistance, EGFR-TKI continuation combined with VEGF inhibitors still had clinical benefits. It is unclear whether the addition of bevacizumab after osimertinib progresses will prolong the duration of the osimertinib benefit. We screened 1289 patients with NSCLC and finally included 96 patients to evaluate osimertinib combined with bevacizumab (osi + bev) versus chemotherapy combined with bevacizumab (che + bev) for patients with acquired resistance to osimertinib. The overall response rate (ORR) for osi + bev and chem + bev was 15.8% (6 of 38) and 20.7% (12 of 58), respectively. The median PFS for osi + bev and che + bev was 7.0 and 4.9 months (HR 0.415 95%CI: 0.252–0.687 p = 0.001). The median OS for osi + bev and che + bev was 12.6 and 7.1 months (HR 0.430 95%CI: 0.266–0.696 p = 0.001). Multivariate analyses showed that no brain metastases and osi + bev treatment after osimertinib resistance correlated with longer PFS (p = 0.044, p = 0.001), while the median PFS of osimertinib less than 6 months (p = 0.021) had a detrimental effect on sequent treatment. Only osi + bev treatment was identified as an independent predictor of OS (p = 0.001). The most common adverse events (AEs) of grade ≥3 were hypertension (13.2%) and diarrhea (10.5%) in the osi + bevacizumab group. Neutropenia (24.1%) and thrombocytopenia (19%) were the most common grade ≥3 AEs in the che + bev group. The overall incidence of serious AEs (grade ≥3) was significantly higher in the chemotherapy plus bevacizumab group. Our study has shown the superiority of osi + bev compared to che + bev after the failure of osimertinib, making it a preferred option for patients with acquired resistance to osimertinib.
Highlights
Lung cancer is the second most commonly diagnosed cancer worldwide and the leading cause of cancer death (Sung et al, 2021)
After the resistance of osimertinib, 38 cases received osimertinib (80 mg daily) rechallenge combined with bevacizumab (30 received 7.5 mg/kg and 8 received 15 mg/kg q3w), and 58 cases received chemotherapy combined with bevacizumab (46 received 7.5 mg/kg and 12 received 15 mg/kg)
While osimertinib has achieved outstanding efficacy in EGFRmutant non–small cell lung cancer (NSCLC) in terms of progression-free survival (PFS) and overall survival (OS), most people inevitably develop resistance, which presents another challenge in the treatment of NSCLC
Summary
Lung cancer is the second most commonly diagnosed cancer worldwide and the leading cause of cancer death (Sung et al, 2021). Compared with the first- and second-generation EGFR-TKIs, first-line osimertinib application has longer progression-free survival (PFS) and overall survival (OS) (Soria et al, 2018; Ramalingam et al, 2020) and has a higher control rate of central nervous system metastases (Reungwetwattana et al, 2018). It has been widely used in the first-line treatment of EGFR-sensitive mutations. For those who cannot access proper clinical trials, platinum-based chemotherapy with or without bevacizumab remains the standard treatment
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