Vintafolide (EC145) for the treatment of folate-receptor-α positive platinum-resistant ovarian cancer

Abstract

Seminal advances in the treatment of cancer have been achieved because of drug development in ovarian cancer; notably the developments of platinums and taxanes. However, no new drug has been FDA approved for ovarian cancer since 2006, and the approval of an antiangiogenic agent for ovarian cancer in the US has stalled. Predicting the next breakthrough is a high risk and highly expensive venture. One of the most promising prospects is folate-receptor (FR)-targeted therapy, given the high expression in FR ovarian cancer. We review the development of vintafolide (EC145), a folic acid-desacetylvinblastine conjugate, the predictive utility of a FR-targeted imaging agent, technetium-⁹⁹m-etarfolatide (EC20), the challenges in proving survival advantage, and other approaches to exploiting FR as a target in ovarian cancer.

Keywords::

• chemotherapy
• EC145
• EC20
• etarfolatide
• novel

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• FR-α expression is a prognostic marker for advanced platinum-resistant ovarian cancer and a potentially important predictive marker of benefit from folate receptor targeted therapy.

• Vintafolide is a high-affinity conjugate of a potent vinca and folic acid. It is internalized via endocytosis, and releases the payload with endosomal degradation of the linker.

• PRECEDENT was a randomized Phase II trial that reported a progression-free survival for vintafolide in platinum-resistant ovarian cancer.

• ⁹⁹mTc-etarfolatide SPECT scanning is being used in the registration study (PROCEED) to identify FR-α positivity.

• Targeted therapy may be better when specific to a particular cancer than to an aspect of cancer biology.

Notes