1330 - Folate receptor-positive circulating tumor cells as a predictive biomarker for the efficacy of first-line pemetrexed-based therapy in patients with non-squamous non-small cell lung cancer

Background

There is a lack of well-established biomarkers to predict the efficacy of pemetrexed-based therapy. In this prospective phase II study, we investigated the correlation of folate receptor (FR)-positive circulating tumor cell (CTC) level with pemetrexed efficacy in patients with advanced non-squamous non-small cell lung cancer (nsNSCLC).

Methods

A total of 98 nsNSCLC patients were enrolled. Peripheral blood was collected from each patient prior to initiation of treatment. FR-positive CTCs were enriched by immunomagnetic leukocyte depletion and quantified using LT-PCR method.

Results

Patients with relatively low CTC level (11-16 FU/3 mL, n = 32) showed a significantly shorter progression-free survival (PFS) and overall survival (OS) compared to the ‘high CTC level group’ (≥16 FU/3 mL, n = 28; median PFS: 133 versus 320 days, hazard ratio[HR]=4.78, P = 0.0008; median OS: 632 days versus ‘not reached’, HR = 10.89, P = 0.0013). The ‘high CTC level group’ also achieved superior objective response rate (ORR) and disease control rate (DCR) over the ‘low CTC level group’ (ORR: 40.9% versus 9.5%, P = 0.0339; DCR: 100% versus 81.0%, P = 0.0485). The efficacy of pemetrexed in the ‘negative-CTC group’ (<11 FU/3 mL, n = 38) falls between the ‘high CTC level group’ and the ‘low CTC level group’ (median PFS: 290 days; median OS: 1122 days; ORR: 21.2%; DCR: 93.9%). When patients received only 1 cycle of treatment (n = 10) were excluded, the differences in both ORR, DCR, and OS between the CTC subgroups were more significant.

Conclusions

Our results implied that FR-positive CTC is an efficacious biomarker to predict the outcome of first-line pemetrexed-based therapy in nsNSCLC patients.

Clinical trial identification

ChiCTR-ONC-13003475.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Pulmonary Hospital.

Funding

This study was partially supported by Shanghai Committee of Science and technology (No. 14411970800). The funder had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Disclosure

All authors have declared no conflicts of interest.