Immunoconjugates against solid tumors: mind the gap.

The objective of immunoconjugate development is to combine the specificity of immunoglobulins with the efficacy of cytotoxic molecules. This therapeutic approach has been validated in hematologic malignancies; however, several obstacles to achieving efficacy in treating solid tumors have been identified. These include insufficient specificity of targets and poor antibody delivery, most specifically to the tumor core. Heterogeneous antigen expression, imperfect vascular supply, and elevated interstitial fluid pressure have been suggested as the factors responsible for the poor delivery of antibodies. Promising immunoconjugates are in development: immunoconjugates targeting the prostate-specific membrane antigen, trastuzumab-DM1, lorvotuzumab mertansine, and SS1P. Advances in cancer biology and antibody engineering may overcome some of the challenges. New small antibody formats, such as single-chain Fv, Fab, and diabodies, may improve penetration within tumor masses. Nevertheless, the cost of treatment might require justification in terms of demonstrable improvement in quality of life in addition to efficacy; further economic evaluation might be necessary before this approach can replace the current standards of care in clinical practice.

CA 19-9 as a biomarker in advanced pancreatic cancer patients randomised to gemcitabine plus axitinib or gemcitabine alone.

BACKGROUND: Response assessment in advanced pancreatic cancer (APC) is difficult and predictive markers are needed. There are insufficient data on the value of carbohydrate antigen 19-9 (CA 19-9) and cytostatic-targeted therapies. Axitinib, a selective vascular endothelial growth factor (VEGF) receptors 1, 2, 3 inhibitor, may increase overall survival (OS) in APC. METHODS: We assessed serum CA 19-9, clinical outcomes and diastolic blood pressure (dBP) in APC patients receiving gemcitabine plus axitinib (Gem+A) or gemcitabine alone. RESULTS: In the total population (N=95), median OS was significantly longer in patients with baseline CA 19-9 values at or below the median than in those with values above it (12.2 months [95% confidence interval (CI), 8.6-16.6%] vs 5.0 months [95% CI, 3.9-5.7%]; P<0.0001). This also reached significance in the Gem+A arm (median OS, 12.5 months [95% CI, 8.6-16.6%] vs 4.9 months [95% CI, 3.6-5.6%]; P<0.0001). Patients with any dBP>90 mmHg had significantly longer OS than those who did not. However, there was no predictive significance of CA 19-9. CONCLUSION: Baseline CA 19-9 levels had prognostic value for OS, but caution is advised in interpreting CA 19-9 as a predictive biomarker for novel cytostatic agents such as VEGF-targeted therapies in phase II studies.