Impact of prolonged and early bevacizumab treatment on the overall survival of EGFR‐mutant and EGFR‐wild type nonsquamous non‐small cell lung cancer

Abstract

BackgroundVEGF plays a key role in tumor angiogenesis and immunosuppression. VEGF‐blocking has proven beneficial for EGFR mutant and wild‐type nonsquamous non‐small cell lung cancer (nonsq‐NSCLC); however, the number of cycles and treatment line yielding the optimal benefit are unknown.MethodsWe retrospectively analyzed the data of 115 patients with advanced/metastatic nonsq‐NSCLC administered at least one cycle of bevacizumab. The number of bevacizumab cycles was treated as a time‐dependent covariate. Predictors of overall survival (OS) were investigated.ResultsBevacizumab was used as first‐line treatment in 47 (40.9%) patients, with a median of five cycles (range: 1–31). Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR] 4.78, 95% confidence interval [CI] 2.68–8.51; P < 0.001), wild‐type EGFR (HR 2.61, 95% CI 1.45–4.70; P = 0.001), and bleeding during bevacizumab treatment (HR 3.63, 95% CI 1.77–7.45; P < 0.001) were predictive of poor OS; the number of bevacizumab cycles and first‐line administration were not. In the wild‐type EGFR subgroup, the number of bevacizumab cycles (≥ 5 vs. 1–4) was associated with a significant OS benefit (HR 0.28, 95% CI 0.08–0.98; P = 0.044); first‐line administration also showed an OS benefit (HR 0.48, 95% CI 0.20–1.17; P = 0.105). A significant association between the number of cycles and EGFR status was identified (P = 0.046).ConclusionOS benefit is negatively affected by bleeding events in bevacizumab‐treated patients. Prolonged and early introduction of bevacizumab may provide an OS benefit for patients with wild‐type EGFR nonsq‐NSCLC.

The optimal timing and courses of bevacizumab added to chemotherapy for non-squamous non-small cell lung cancer: revelations from the real-world experience in a single Chinese cancer center

“…Besides, the two independent factors associated with PFS with Bev plus chemotherapy were revealed in our studylines of Bev (Bev + Che1 vs. Bev + Che2/3) and courses of bevacizumab (>6 vs. ≤6), which was consistent with the differences of DCR in the corresponding groups and can independently predict the PFS benefit regardless of driver gene status, previous targeted therapy, and the other factors studied in our study, providing valuable information for therapeutic decision-making in clinical practice. It has been reported that the wild-type EGFR was a predictor of poor OS in NSCLC patients treated with Bev plus chemotherapy (17). However, the status of EGFR and prior TKI had no independent impact on the survival of our data.…”

The Combination of Afatinib and Bevacizumab in Untreated EGFR-Mutated Advanced Lung Adenocarcinoma: A Multicenter Observational Study

“…In all previous trials, bevacizumab was administered at a dose of 15 mg/kg [15][16][17][18], which is different from the 7.5 mg/kg dose administered to most of the patients in our study. In Taiwan, bevacizumab is not covered by the National Health Insurance for lung cancer therapy [14,22]. The cost-effectiveness of adding bevacizumab to advanced lung adenocarcinoma treatment thus depends on the physician's judgment and the patient's financial resources [22].…”

“…Bevacizumab is the first anti-angiogenesis inhibitor approved for the treatment of metastatic non-squamous lung cancer, according to the results of two previous clinical trials (E4599 and AVAIL trials) [11,12]. Previous clinical studies have shown that bevacizumab in combination with chemotherapy or EGFR-TKIs provides a survival benefit for patients with advanced lung cancer [13,14]. Combinations of first-generation EGFR-TKIs, including gefitinib and erlotinib, with bevacizumab in EGFR-mutated advanced NSCLC have been explored in clinical trials (JO25567 and NEJ026 trials), and the combination has been found to yield significantly longer PFS than EGFR-TKIs alone [15][16][17].…”

The different overall survival between single-agent EGFR-TKI treatment and with bevacizumab in non-small cell lung cancer patients with brain metastasis

“…The dose of EGFR-TKI administered were gefitinib 250 mg/day and erlotinib 150 mg/day, respectively; and bevacizumab was administered at a dose of 7.5 mg/kg every 3 weeks. The lower dose strength was chosen because bevacizumab is not reimbursed by National Health Insurance of Taiwan for NSCLC treatment and this dosage has been demonstrated to achieve an equivalent efficacy and numerically lower adverse events compared to the 15 mg/kg dose strength 22 , 23 Patients were excluded if the first dose of bevacizumab was given 3 weeks behind the first dose of EGFR-TKI and those who received an EGFR-TKI monotherapy less than 14 days were also excluded. The progression-free survival (PFS) was defined as the interval between the date of starting EGFR-TKI treatment and the date of radiologically or clinically determined progression or death.…”