Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer.

Background: Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified.
Methods: A total of 184 mCRC patients progressing to a first-line bevacizumab-containing treatment were randomised in the BEBYP study to continue or not the antiangiogenic in combination with a second-line chemotherapy. A subgroup analysis according to baseline serum lactate dehydrogenase (LDH) levels was carried out.
Results: A significant interaction effect between LDH levels and treatment was found in terms of progression-free survival (PFS; P=0.002). Although patients with low LDH levels achieved significant PFS benefit from the continuation of bevacizumab (HR: 0.39 (95% CI: 0.23-0.65)), patients with high levels did not (HR: 1.10 (95% CI: 0.74-1.64)). Consistent results were reported in overall survival (OS; P=0.075).
Conclusions: As preclinical evidence suggests that serum LDH may be a marker of tumour angiogenesis activation, low levels may indicate that bevacizumab is still efficacious in inhibiting angiogenesis. Validation of present results in subgroup analyses of other randomised trials of second-line angiogenesis inhibitors is warranted.
Competing Interests: LA reports serving on advisory board or having consultant role for Roche, Amgen, Eli-Lilly, Bayer, Novartis, Ipsen; FL reports serving on advisory board for Amgen and Sanofi-Aventis, receiving lecture fees from Sanofi-Aventis, Bayer, Roche and grant support from Roche and Merck Serono; AF reports serving on advisory board for Amgen, Bayer, Merck Serono, Roche and Sanofi-Aventis, receiving lecture fees from Merck Serono, Roche, Amgen, Bayer, Amgen, Bayer, Merck Serono, Roche and Sanofi-Aventis and grant support from Amgen, Merck Serono and Roche; CC reports serving on advisory board for Roche, Bayer, Amgen and Merck Serono and receiving lecture fees from Sanofi-Aventis and Bayer. All remaining authors declared no conflicts of interest.