PRONOUNCE: Randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer

Ralph G. Zinner, Coleman K. Obasaju, David R. Spigel, Robert W. Weaver, J. Thaddeus Beck, David M. Waterhouse, Manuel R. Modiano, Borys Hrinczenko, Petros G. Nikolinakos, Jingyi Liu, Andrew G. Koustenis, Katherine B. Winfree, Symantha A. Melemed, Susan C. Guba, Waldo I. Ortuzar, Durisala Desaiah, Joseph A. Treat, Ramaswamy Govindan, Helen J Ross

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Abstract

Introduction: PRONOUNCE compared the efficacy and safety of pemetrexed+carboplatin followed by pemetrexed (Pem+Cb) with paclitaxel+carboplatin+bevacizumab followed by bevacizumab (Pac+Cb+Bev) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). Methods: Patients ≥18 years of age with stage IV nonsquamous NSCLC (American Joint Committee on Cancer v7.0), and Eastern Cooperative Oncology Group performance status 0/1 were randomized (1:1) to four cycles of induction Pem+Cb (pemetrexed, 500 mg/m<sup>2</sup>, carboplatin, area under the curve = 6) followed by Pem maintenance or Pac+Cb+Bev (paclitaxel, 200 mg/m<sup>2</sup>, carboplatin, area under the curve = 6, and bevacizumab, 15 mg/kg) followed by Bev maintenance in the absence of progressive disease or discontinuation. The primary objective was progression-free survival (PFS) without grade 4 toxicity (G4PFS). Secondary end points were PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety. Resource utilization was also assessed. Results: Baseline characteristics of the patients randomized to Pem+Cb (N = 182) and Pac+Cb+Bev (N = 179) were well balanced between the arms. Median (months) G4PFS was 3.91 for Pem+Cb and 2.86 for Pac+Cb+Bev (hazard ratio = 0.85, 90% confidence interval, 0.7-1.04; p = 0.176); PFS, OS, ORR, or DCR did not differ significantly between the arms. Significantly more drug-related grade 3/4 anemia (18.7% versus 5.4%) and thrombocytopenia (24.0% versus 9.6%) were reported for Pem+Cb. Significantly more grade 3/4 neutropenia (48.8% versus 24.6%), grade 1/2 alopecia (28.3% versus 8.2%), and grade 1/2 sensory neuropathy were reported for Pac+Cb+Bev. Number of hospitalizations and overall length of stay did not differ significantly between the arms. Conclusions: Pem+Cb did not produce significantly better G4PFS compared with Pac+Cb+Bev. Pem+Cb was not superior in PFS, OS, ORR, or DCR compared with Pac+Cb+Bev. Both regimens were well tolerated, although, toxicity profiles differed.

Original languageEnglish (US)
Pages (from-to)134-142
Number of pages9
JournalJournal of Thoracic Oncology
Volume10
Issue number1
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Advanced nonsquamous non-small-cell lung cancer
  • Bevacizumab
  • Carboplatin
  • Combination therapy
  • Efficacy
  • Paclitaxel
  • Pemetrexed
  • Safety

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Zinner, R. G., Obasaju, C. K., Spigel, D. R., Weaver, R. W., Beck, J. T., Waterhouse, D. M., Modiano, M. R., Hrinczenko, B., Nikolinakos, P. G., Liu, J., Koustenis, A. G., Winfree, K. B., Melemed, S. A., Guba, S. C., Ortuzar, W. I., Desaiah, D., Treat, J. A., Govindan, R., & Ross, H. J. (2015). PRONOUNCE: Randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. Journal of Thoracic Oncology, 10(1), 134-142. https://doi.org/10.1097/JTO.0000000000000366