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ORAL 01 - Chemotherapy Developments for Lung Cancer (ID 88)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
ORAL01.03 - A Randomized Phase 2 Trial of Vintafolide and Docetaxel in Folate-Receptor Positive (FR+) Advanced NSCLC Patients: Final Efficacy Results (ID 1600)
10:45 - 12:15 | Author(s): O. Gladkov
Vintafolide (folic acid-vinca alkaloid conjugate) binds to the folate receptor (FR), which is overexpressed in approximately 80% of patients with NSCLC, including patients with squamous cell and adenocarcinoma. Using the molecular imaging agent 99mTc-etarfolatide for SPECT imaging, the FR status of malignant lesions can be determined. Vintafolide has demonstrated single agent activity in patients with advanced NSCLC whose tumors all expressed FR [FR(100%)] compared to patients not FR(100%) (Edelman et al, 2012).
This study randomized patients with advanced NSCLC whose tumors were FR(100%) to vintafolide, vintafolide + docetaxel, or docetaxel. Key eligibility criteria: age ≥18 years; 1 prior systemic therapy for advanced disease; ECOG PS 0-1. Patients underwent [99m]Tc-etarfolatide SPECT screening for FR assessment. Vintafolide (2.5 mg) was administered on days 1, 4, 8, 11 every 21 days and docetaxel (75 mg/m) on day 1 every 21 days. The primary endpoint was progression-free survival (PFS). Pre-specified PFS comparisons were performed for vintafolide vs docetaxel and vintafolide+docetaxel vs docetaxel in all patients as well as those with adenocarcinoma. Significance testing for each PFS analysis was one-sided without adjustment for multiplicity (alpha=0.10). Overall survival (OS) was a secondary endpoint.
Over 14 months, 199 FR(100%) patients were randomized and treated (vintafolide: 63; vintafolide+docetaxel: 68; docetaxel: 68). Patient and disease characteristics were well-balanced between arms. The vintafolide+docetaxel arm met the primary endpoint of superior PFS over the docetaxel arm in all patients regardless of histology (17.0% censored; unstratified Cox model hazard ratio [HR] =0.75; unstratified one-sided p-value=0.0696) as well as in the prespecified 133 patient adenocarcinoma subgroup (18.8% censored; HR=0.73; p-value=0.0899). Trends in OS favored the vintafolide+docetaxel arm over the docetaxel arm in all patients (37.7% censored; HR=0.88; p-value=0.2874) and showed the greatest benefit in the adenocarcinoma subgroup (42.8% censored; HR=0.70; p-value=0.1018). The single-agent vintafolide arm was not superior to docetaxel. Vintafolide+docetaxel treatment was associated with more neutropenia (all grades: 77% versus 62%), febrile neutropenia (13% versus 6%), and peripheral neuropathy (34% versus 21%) compared to docetaxel alone.
The addition of vintafolide to docetaxel resulted in a statistically significant improvement in PFS in FR(100%) NSCLC patients regardless of histology (PFS HR= 0.75) and in the adenocarcinoma subset (PFS HR= 0.73). Additionally, there was a trend towards improvement in OS in all patients regardless of histology (OS HR= 0.88) and in the adenocarcinoma subset (OS HR= 0.70). Vintafolide +docetaxel was generally well tolerated, although rates of neutropenia, neutropenic fever, and neuropathy were higher than with docetaxel alone. Final survival results will be presented at the conference.
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