1251P - Front-line chemotherapy with or without NGR-HTNF in non-small cell lung cancer (NSCLC)

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Drug Development
Non-Small-Cell Lung Cancer, Metastatic
Presenter Vanesa Gregorc
Authors V. Gregorc1, N. Zilembo2, F. Grossi3, T. De Pas4, F. Pietrantonio5, M. Giovannini6, G.M. Rossoni7, A. Bulotta7, A. Lambiase8, C. Bordignon8
  • 1Oncologia, IRCCS San Raffaele, IT-20132 - Milano/IT
  • 2Department Of Oncology, IRCCS Fondazione Istituto Nazionale dei Tumori, Milan/IT
  • 3Medical Oncology A, Istituto Nazionale per la Ricerca sul Cancro, Genoa/IT
  • 4Istituto Europeo di Oncologia, Milan/IT
  • 5Oncologia Medica 1, IRCCS Fondazione Istituto Nazionale dei Tumori, Milan/IT
  • 6Unit Of Respiratory Tract And Sarcomas, Istituto Europeo di Oncologia, Milan/IT
  • 7IRCCS San Raffaele, IT-20132 - Milano/IT
  • 8Clinical Development, MolMed, 20132 - Milan/IT

Abstract

Background

NGR-hTNF (asn-gly-arg-human tumor necrosis factor) is a selective vascular targeting agent able to improve intratumoral chemotherapy uptake.

Methods

After stratification by histology (nonsquamous or squamous) and PS (0 or 1), previously untreated patients (pts) with advanced NSCLC were randomly assigned to receive cisplatin 80 mg/m2/d1 plus either pemetrexed 500 mg/m2/d1 (nonsquamous) or gemcitabine 1,250 mg/m2/d1 + 8 (squamous) q3w for 6 cycles with (arm A) or without (arm B) NGR-hTNF 0.8 µg/m2/d1 q3w given until progression. Progression-free survival (PFS) was primary endpoint of this phase 2 trial (� = 20%, α = 20%, n = 102). Secondary endpoints included adverse events (AEs), overall survival (OS), and response rate (RR).

Results

Baseline characteristics in arm A (n = 61) v B (n = 58): median age 62 v 63 years; male 36 v 38; PS of 1 22 v 22; squamous 17 v 16; nonsmokers 19 v 14; EGFR mutations 5 v 5. For the nonsquamous stratum, 295 cycles were given in A (mean 6.9; range 1-18) and 192 in B (4.8; 1-6), while for the squamous stratum, 95 in A (6.3; 1-24) and 49 in B (3.5; 1-6). The rates of grade 3 to 4 AEs were comparable in arm A v B: neutropenia 14% v 17% and fatigue 7% v 11%. Neither grade 3 to 4 AEs related to NGR-hTNF nor bleeding in pts with squamous histology were noted. With a median follow-up of 16.4 months for all pts, median PFS was 5.8 v 5.6 months, 1-year OS rate was 58% v 56%, and RR was 25% v 21% in arm A v B, respectively. For the nonsquamous stratum, trends toward higher 6-month PFS rates for arm A v B were noted in pts with PS 1 (65% v 33%), nonsmoking history (59% v 33%), younger age (64% v 30%), and EGFR mutations (75% v 25%). Similarly, in these pts the 1-year OS rates were: PS 1 (60% v 56%), nonsmoking history (77% v 65%), younger age (75% v 63%), and EGFR mutations (100% v 50%). For the squamous stratum, median PFS was 5.6 v 4.3 months (HR = 0.71) and median OS was 14.2 v 10.2 months (HR = 0.54) for arm A v B, respectively. In these pts, RR was 36% for arm A and 23% for arm B, while median changes from baseline in target tumor size after 2, 4, and 6 cycles were -27%, -39%, and -33%, respectively for arm A, and -18%, -22%, and -14%, respectively for arm B.

Conclusion

NGR-hTNF can be safely given with standard chemotherapy and may have therapeutic potential in squamous NSCLC

Disclosure

A. Lambiase: Employment - MolMed.

C. Bordignon: Employment - MolMed.

All other authors have declared no conflicts of interest.