NGR-hTNF plus chemotherapy as first-line therapy of non-small cell lung cancer (NSCLC)

7581 Background: NGR-hTNF (asparagine-glycine-arginine human tumor necrosis factor) is a selective vascular targeting agent able to improve intratumoral chemotherapy uptake. Methods: Chemo-naive, stage IIIb-IV NSCLC patients (pts), stratified by histology (nonsquamous or squamous) and PS (0 or 1), were randomized to cisplatin 80 mg/m2/day(d)1 plus either pemetrexed 500 mg/m2/d1 (nonsquamous) or gemcitabine 1,250 mg/m2/d1+8 (squamous) every 3 weeks (q3w) up to 6 cycles with (arm A) or without (arm B) NGR-hTNF 0.8 μg/m2/d1 q3w until progression. Progression free survival (PFS) was primary end point of this phase 2 trial (β=20%, α=20%, HR=0.62, and n=102). Secondary end points included adverse events (AEs), response rate (RR) and overall survival (OS). Results: 59 pts were assigned to arm A and 57 to arm B. Baseline characteristics in arm A/B were: median age 62/63; male 34/37; PS 1 21/21; squamous 15/15; nonsmokers 14/12; EGFR mutations 5/5. For the nonsquamous group, 281 cycles (mean 6.5; range 1-18) were given in arm A and 190 (mean 4.7; range 1-6) in arm B, while for the squamous group, 88 (mean 6.3; range 1-19) in arm A and 48 (mean 3.7; range 1-6) in arm B. Most common grade 3/4 AEs were neutropenia 14% vs 17% and fatigue 7% vs 11% in arm A and B, respectively. No grade 3/4 AEs related to NGR-hTNF or bleeding in pts with squamous histology were noted. Median follow-up was 12.4 months. In the whole study population, median (m)PFS was 5.8 vs 5.7 months (HR=0.95), RR was 23% vs 19%, and 1-year OS was 62% vs 62% in arm A and B, respectively. In the nonsquamous subset, a trend toward longer mPFS in arm A compared to arm B was noted in pts with a PS of 1 (6.7 vs 4.6 months, respectively), nonsmoking history (6.2 vs 3.4), younger age (6.5 vs 3.4), and EGFR mutations (7.2 vs 3.3). In the squamous subset, mPFS was 5.1 vs 3.9 months (HR=0.71) and mOS was 14.2 vs 10.8 months (HR=0.73) in arm A and B, respectively. In these pts, ORR was 36% in arm A and 23% in arm B, while median changes from baseline in target tumor size after 2, 4, and 6 cycles were -29%, -45%, and -41%, respectively in arm A, and -18%, -22%, and -14%, respectively in arm B. Conclusions: Regardless of histology, NGR-hTNF can be safely given with standard chemotherapy, showing tolerability and hint of activity in squamous NSCLC.