Alectinib plus bevacizumab in ALK-rearranged non-small cell lung cancer

The results of ALEK-B phase II trial, recently published on Nature Communications, support the efficacy and safety of alectinib plus bevacizumab in ALK-rearranged non-small cell lung cancer (NSCLC).

ALEK-B trial was designed to investigate whether combining alectinib with bevacizumab can delay resistance mechanisms in advanced ALK-rearranged NSCLC. This single-arm study involved 41 patients with advanced ALK-rearranged NSCLC, including 17.1% with brain metastases, treated with first-line alectinib and bevacizumab. The first reported outcomes, with a median follow-up of 15.6 months, indicated a 12-month progression free survival rate of 97.1%; these new data, at a median follow-up of 34.5 months, show a progression free survival rate of 64.2% and an overall survival rate of 87.9%. The overall response rate was 100% whereas grade 3–4 adverse events occurred in 46.3% of patients, most commonly proteinuria and hepatotoxicity. Quality of life significantly improved from baseline at 12 months and was maintained through 36 months. «The addition of bevacizumab to alectinib significantly prolonged progression-free survival and effectively prevented early systemic and central nervous system progression events in patients with advanced ALK-positive NSCLC, regardless of the presence of brain metastases at baseline», authors say. «This combination induced profound and durable responses without compromising quality of life. While the toxicity profile was higher than expected, no permanent damage or treatment-related deaths were reported. Limiting the number of antiangiogenic cycles may mitigate these issues».