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NSCLC, metastatic

5032 - A Phase II, randomised, open-label study of Gemcitabine/Carboplatin first-line chemotherapy in combination with or without the antisense oligonucleotide Apatorsen (OGX-427) in advanced squamous cell lung cancers

Date

10 Sep 2017

Session

NSCLC, metastatic

Presenters

Peter Schmid

Citation

Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440

Authors

P. Schmid1, F. Blackhall2, D. Muthukumar3, J. Lester4, S. Khan5, J. Adams6, M. Illsley7, C. Macgregor8, W. Owadally9, S. Sarker10, L. Smith1, A. Prendergast1, C. Ackerman1, K. Mousa1, L. Lim Farah11

Author affiliations

  • 1 Centre For Experimental Cancer Medicine, Barts Cancer Institute-Queen Mary University of London, EC1M 6BQ - London/GB
  • 2 The Christie Nhs Foundation Trust And Division Of Molecular And Clinical Cancer Services, University of Manchester, M20 4BX - Manchester/GB
  • 3 Clinical Oncology, Colchester Hospital University Essex County Hospital, CO3 3NB - Colchester/GB
  • 4 Oncology, Velindre, Wales/GB
  • 5 Oncology, Nottingham University Hospital, Nottingham/GB
  • 6 Oncology, Royal Berkshire Hospital - NHS Foundation Trust, RG1 5AN - Reading/GB
  • 7 Oncology, Royal Surrey County Hospital, Guildford/GB
  • 8 Oncology, NHS Highland, Inverness/GB
  • 9 Oncology, University Hospitals Bristol NHS Trust Bristol Haematology and Oncology Centre, BS2 8ED - Bristol/GB
  • 10 Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ - London/GB
  • 11 Oncology, St. Bartholomew's Hospital, EC1A 7BE - London/GB
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Abstract 5032

Background

Outcomes remain poor for patients with advanced squamous-cell non-small cell lung cancer (SCC). Chemotherapy remains the standard 1st line treatment, but benefits are often transient with rapid development of resistance. Heat shock protein 27 (Hsp27) plays a role in apoptosis evasion and is highly expressed in 70-98% of SCCs. Induction of Hsp27 by chemotherapy can be an early compensatory mechanism associated with resistance that can be exploited therapeutically to increase the efficacy of chemotherapy. Apatorsen (OGX-427) is a second generation antisense oligonucleotide that effectively down-regulates Hsp27 in vitro and in vivo. This study investigated whether the combination of Apatorsen and chemotherapy (GC+A) can improve the outcome of patients with advanced SCC compared to treatment with gemcitabine/carboplatin (GC) alone.

Methods

This is a multicentre investigator led, randomised (1:1), open-label phase 2 trial, stratified by stage and performance status. A total of 86 patients with newly diagnosed Stage IIIB/IV SCC received up to 6 cycles of gemcitabine (1250 mg/m2) and carboplatin (AUC5) with or without Apatorsen (600 or 400 mg IV/week) until disease progression. Tumour evaluation took place q6 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety, Objective response rate (ORR), disease control rate (DCR) and overall survival (OS).

Results

With a median follow up of 20.8 months, there was no difference between both treatment arms in PFS (median PFS, GC 5.7 mths, GC+A 4.9 mths; HR 0.84; 95% CI 0.54, 1.31; p = 0.40) or OS (median OS, GC 11.4 mths, GC+A 8.5 mths; HR 0.68, 95% CI 0.41, 1.13; p = 0.11). ORR was 42% for GC and 33% for GC+A (p = 0.37). DCR was 56% for GC and 42% for GC+A (p = 0.2). There was no difference in chemotherapy dose intensity between both treatment groups. GC+A was associated with increased toxicity compared to GC alone with myelosuppression and infection being most comments adverse events.

Conclusions

This trial failed to demonstrate a benefit for adding apatorsen to standard chemotherapy in newly diagnosed SCC.

Clinical trial identification

EudraCT Number: 2014-000199-25, Clinicaltrials.gov Identifier: NCT02423590

Legal entity responsible for the study

Queen Mary University of London

Funding

OncoGenex Pharmaceuticals Inc.

Disclosure

All authors have declared no conflicts of interest.

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