Selumetinib in patients receiving standard pemetrexed and platinum-based chemotherapy for advanced or metastatic KRAS wildtype or unknown non-squamous non-small cell lung cancer: A randomized, multicenter, phase II study. Canadian Cancer Trials Group (CCTG) IND.219 Academic Article uri icon

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abstract

  • INTRODUCTION: Activation of the RAS/RAF/MEK/ERK pathway may confer resistance to chemotherapy in non-small cell lung cancer (NSCLC). Selumetinib (AZD6244, ARRY142886), a MEK1/2 inhibitor combined with chemotherapy in patients with NSCLC was evaluated in two schedules to evaluate efficacy and toxicity. METHODS: IND.219 was a three-arm study of first line pemetrexed/platinum chemotherapy with two schedules of selumetinib (Arm A: intermittent given on days 2-19; Arm B: continuous given on days 1-21) versus chemotherapy alone (Arm C). The primary endpoint was objective response rate (ORR); secondary objectives were tolerability, progression-free survival (PFS), overall survival (OS). The trial was stopped at the planned interim analysis. RESULTS: Arms A/B/C enrolled 20/21/21 patients, ORR was 35% (95% CI 15-59% median duration 3.8 months), 62% (95% CI 38-82%; median duration 6.3 months), 24% (95% CI 8-47%; median duration 11.6 months) respectively. The PFS (months Arm A, B, C) was 7.5, 6.7, 4.0 respectively (hazard ratio (HR) PFS Arm A over Arm C: 0.76 [95% CI, 0.38-1.51, 2-sided p = 0.42]; Arm B over Arm C 0.75 [95% CI 0.37-1.54, p = 0.43]. Skin and gastrointestinal adverse events were more common with the addition of selumetinib. A high incidence of venous thromboembolism was seen in all arms. CONCLUSIONS: Selumetinib combined with chemotherapy was associated with a higher response rate. Continuous selumetinib appeared to be superior to an intermittent schedule. PFS was prolonged with the addition of selumetinib, however this was not statistically significant.

authors

  • Melosky, Barbara
  • Bradbury, Penelope
  • Tu, Dongsheng
  • Florescu, Marie
  • Reiman, Anthony
  • Nicholas, Garth
  • Basappa, Naveen
  • Rothenstein, Jeffrey
  • Goffin, John
  • Laurie, Scott A
  • Wheatley-Price, Paul
  • Leighl, Natasha
  • Goss, Glenwood
  • Reaume, M Neil
  • Butts, Charles
  • Murray, Nevin
  • Card, Cynthia
  • Ko, Jenny
  • Blais, Normand
  • Gray, Samantha
  • Lui, Hongbo
  • Brown-Walker, Pamela
  • Kaurah, Pardeep
  • Prentice, Leah M
  • Seymour, Lesley

publication date

  • July 2019

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