G Giaccone1, L A Bazhenova2, J Nemunaitis3, M Tan4, E Juhász5, R Ramlau6, M M van den Heuvel7, R Lal8, G H Kloecker9, K D Eaton10, Q Chu11, D J Dunlop12, M Jain13, E B Garon14, C S Davis15, E Carrier16, S C Moses16, D L Shawler16, H Fakhrai16. 1. National Cancer Institute, Bethesda, MD, USA. Electronic address: gg496@georgetown.edu. 2. Moores Cancer Center, UC San Diego, La Jolla, CA, USA. 3. Mary Crowley Cancer Research Centers, Dallas, TX, USA. 4. Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. 5. Korányi National Institute for TB and Pulmonology, Budapest, Hungary. 6. Wielkopolskie Centrum Pulmonologii i Torakochirurgii, Poznań University of Medical Sciences, Poznan, Poland. 7. Netherlands Cancer Institute, Antoni Van Leeuwenhoek Hospital, Thoracic Oncology, Amsterdam, Netherlands. 8. Guy's Hospital, King's Health Partners, London, England, United Kingdom. 9. James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA. 10. Seattle Cancer Care Alliance, University of Washington, Seattle, WA, USA. 11. Cross Cancer Institute, Edmonton, Alberta, Canada. 12. Royal Infirmary, Glasgow, Scotland, United Kingdom. 13. Noble Hospital, Pune, India. 14. University of California, Los Angeles, Los Angeles, CA, USA. 15. CSD Biostatistics, Tucson, AZ, USA. 16. NovaRx Corporation, San Diego, CA, USA.
Abstract
BACKGROUND: Treatment options after first-line chemotherapy are limited in non-small cell lung cancer (NSCLC). Belagenpumatucel-L is a therapeutic vaccine comprised of 4 transforming growth factor (TGF)-β2-antisense gene-modified, irradiated, allogeneic NSCLC cell lines that may be useful for maintenance after initial treatment. METHODS: Stage III/IV NSCLC patients who did not progress after platinum-based chemotherapy were randomised 1:1 to receive maintenance belagenpumatucel-L or placebo. Patients were eligible for randomisation between one and four months from the end of induction chemotherapy. The primary endpoint was overall survival. RESULTS: This phase III trial enrolled 270 patients in the belagenpumatucel-L arm and 262 in the control arm. Belagenpumatucel-L was well tolerated with no serious safety concerns. There was no difference in survival between the arms (median survival 20.3 versus 17.8months with belagenpumatucel-L versus placebo, respectively; hazard ratio (HR) 0.94, p=0.594). There were also no differences in progression-free survival (4.3months versus 4.0 for belagenpumatucel-L vs placebo, respectively; HR 0.99, p=0.947). A prespecified Cox regression analysis demonstrated that the time elapsed between randomisation and the end of induction chemotherapy had a significant impact on survival (p=0.002) and that prior radiation was a positive prognostic factor (median survival 28.4months with belagenpumatucel-L versus 16.0months with placebo; HR 0.61, p=0.032). CONCLUSIONS: Although the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted.
RCT Entities:
BACKGROUND: Treatment options after first-line chemotherapy are limited in non-small cell lung cancer (NSCLC). Belagenpumatucel-L is a therapeutic vaccine comprised of 4 transforming growth factor (TGF)-β2-antisense gene-modified, irradiated, allogeneic NSCLC cell lines that may be useful for maintenance after initial treatment. METHODS: Stage III/IV NSCLCpatients who did not progress after platinum-based chemotherapy were randomised 1:1 to receive maintenance belagenpumatucel-L or placebo. Patients were eligible for randomisation between one and four months from the end of induction chemotherapy. The primary endpoint was overall survival. RESULTS: This phase III trial enrolled 270 patients in the belagenpumatucel-L arm and 262 in the control arm. Belagenpumatucel-L was well tolerated with no serious safety concerns. There was no difference in survival between the arms (median survival 20.3 versus 17.8months with belagenpumatucel-L versus placebo, respectively; hazard ratio (HR) 0.94, p=0.594). There were also no differences in progression-free survival (4.3months versus 4.0 for belagenpumatucel-L vs placebo, respectively; HR 0.99, p=0.947). A prespecified Cox regression analysis demonstrated that the time elapsed between randomisation and the end of induction chemotherapy had a significant impact on survival (p=0.002) and that prior radiation was a positive prognostic factor (median survival 28.4months with belagenpumatucel-L versus 16.0months with placebo; HR 0.61, p=0.032). CONCLUSIONS: Although the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted.
Authors: M Majem; J Hernández-Hernández; F Hernando-Trancho; N Rodríguez de Dios; A Sotoca; J C Trujillo-Reyes; I Vollmer; R Delgado-Bolton; M Provencio Journal: Clin Transl Oncol Date: 2019-06-06 Impact factor: 3.405