According to research published in the Journal of clinical Oncology, the onset of high blood pressure (HBP) during treatment with bevacizumab in combination with carboplatin and paclitaxel (PCB) may be associated with improved clinical outcomes among patients with advanced non-squamous non-small-cell lung cancer (NSCLC).

Because bevacizumab is postulated to decrease nitric oxide synthesis, leading to hypertension, which in turn may be a physiological sign that the VEGF pathway is more actively being blocked researchers evaluated whether patients showing signs of hypertension would be more likely to derive improved outcomes.

The ECOG 4599 was a phase III trial in which patients (n = 878) with advanced non-squamous NSCLC were randomly assigned to first-line therapy of carboplatin (area under the concentration-time curve, 6 mg/mLXmin, day 1) and
paclitaxel (200 mg/m2, day 1) with or without bevacizumab (15 mg/kg, day 1; PCB vs. PC) on a 21-day treatment cycle. Hypertensive patients were compared with non-hypertensive patients with respect to overall survival (OS) and progression-free survival (PFS) using blood pressure data and adverse event data separately.

The following results were reported:

• Adjusting for HBP as a time-varying covariate, comparing those on PCB with HBP with those on PC gave an OS hazard ratio (HR) of 0.60 (95% CI, 0.43 to 0.81; P = 0.001)
• Comparing those on PCB without HBP with those on PC alone, the OS HR was 0.86 (95% CI, 0.74 to 1.00; P = 0.05).
• Comparing the PCB HBP group with PC gave an adjusted PFS HR of 0.54 (95% CI, 0.41 to 0.73; P < .0001) and comparing those on PCB without HBP to those on PC, the HR was 0.72 (95% CI, 0.62 to 0.84; P < 0.0001).

The researchers also conclude that this study supports the hypothesis that the onset of hypertension during treatment with bevacizumab correlates with antitumour activity and superior outcome, and hypertension does not necessitate a dose reduction of bevacizumab because reducing tumour burden remains the top priority, the risks of which outweigh the risks of hypertension.