Folate Level IDs Patients for New NSCLC Chemo (CME/CE)
Development of the conjugate and receptor test evolved from recognition that several types of cancer cells express folate receptor on the surface, including NSCLC.
Vintafolide consists of folic acid linked to the potent vinca alkaloid desacetylvinblastine hydrazide.
The folate component of the drug binds to cancer cell surface receptors, giving the chemotherapeutic component access to the intracellular environment.
To aid in targeting the drug conjugate, investigators developed a test consisting of technetium-labeled folate (99mTc-etarfolatide, EC20).
Clinical and preclinical experience with the test showed that some tumors exhibit only partial expression of folate receptor and others express the receptor in all cells.
Testing with etarfolatide showed that 11 patients did not have folate receptor-expressing tumors, 16 had at least one lesion with receptor expression, and in the remaining 16 patients, all target lesions expressed folate receptor.
Because prior experience showed that folate receptor-negative tumors were not sensitive to vintafolide, investigators administered the conjugate only to patients with partial or complete folate receptor expression.
The primary objective was the proportion of patients achieving clinical benefit, defined as having received at least four cycles of treatment with vintafolide.
Edelman reported data for 28 evaluable patients, 14 each with complete or partial folate receptor expression.
Seven of 14(50%) patients with complete receptor expression met the primary endpoint versus two of 14 (14.3%) patients who had incomplete receptor expression.
All other outcome parameters showed substantial advantages for the group with complete expression: Objective response rate: 7.1% versus 0% Disease control rate: 57.1% versus 14.3% Median progression-free survival: 31.1 weeks versus 7.3 weeks (HR 0.326 ( P =0.034) Median overall survival: 47.2 weeks versus 14.9 weeks (HR 0.539, P =0.203)