Toxicity limits benefits of bevacizumab–erlotinib NSCLC maintenance therapy

By Sara Freeman, medwireNews Reporter

Two targeted anticancer drugs used together after first-line chemotherapy for advanced stage non-small-cell lung cancer (NSCLC) improve progression-free survival (PFS), the results of a large, prospective study show.

Median PFS was 4.8 months for patients treated with bevacizumab plus erlotinib versus 3.7 months for those treated with bevacizumab plus placebo (hazard ratio [HR] = 0.71).

There was no overall survival (OS) advantage, however, and the two-drug combination was associated with more adverse events than bevacizumab alone, say the study investigators.

Bruce Johnson (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and colleagues explain that the rationale for combining these two drugs is that they “target different molecular pathways involved in tumorigenesis.” They also note, in the Journal of Clinical Oncology, that phase I and II studies had suggested that the combination was associated with good tolerability and a promising antitumor effect.

The current phase III study they conducted involved 743 patients with advanced NSCLC who had received four cycles of platinum-based chemotherapy plus bevacizumab and who were then randomly assigned to continue treatment with bevacizumab with the addition of either erlotinib or placebo.

The median age of patients was 64 years, 85% had stage IV NSCLC, with the remainder having stage IIIb (9%) or recurrent (6%) disease. The majority (82%) had adenocarcinomas.

“The reduction in risk of disease progression or death for clinically important subgroups was consistent with the overall treatment effect,” Johnson et al report.

As expected, they found that there was a greater (HR=0.44) PFS benefit of the two-drug combination versus bevacizumab alone in patients with an activating epidermal growth factor receptor (EGFR) mutation, which erlotinib specifically targets. A similar OS benefit for the combination was seen in patients with an activating EGFR mutation.

Any grade of adverse event occurred in 95.9% of patients given the two-drug combination and 86.9% of those given bevacizumab plus placebo. Grade 3 adverse events occurring in more patients treated with bevacizumab plus erlotinib versus bevacizumab plus placebo included rash (6.8 vs 0.5%) and diarrhea (9.8 vs 1.9%).

Noting that overall there was a modest impact on PFS and markedly increased toxicity, the researchers conclude that “this two-drug maintenance regimen will not lead to a new postchemotherapy standard of care.”

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