ASCO 2020 – Metastatic NSCLC: no clear benefit with chemo add-on to durvalumab+tremelimumab


  • Cristina Ferrario — Agenzia Zoe
  • Oncology Conference reports
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Takeaway

  • OS was not improved with the addition of chemotherapy (CT) to firstline treatment with durvalumab (D) plus tremelimumab (T) for high-risk, metastatic NSCLC.
  • CT add-on yielded better objective response rate (ORR) and progression-free survival (PFS) vs DT alone but was associated with greater toxicity in this trial.

Why this matters

  • Studies of dual checkpoint inhibition NSCLC have shown additive or synergistic activity and better survival vs CT.
  • The optimal use and combination of checkpoint inhibitors with CT in the treatment of stage IV NSCLC remain uncertain.

Study design

  • 301 patients with squamous or nonsquamous stage IV NSCLC, EGFR/ALK wildtype, were included in the international, open-label, randomized CCTG BR.34 trial.
  • Patients were randomly assigned to 4 cycles of DT or DT+CT (pemetrexed- or gemcitabine-platinum), followed by D or D+pemetrexed (nonsquamous) maintenance until disease progression.
  • Primary endpoint: OS.
  • Secondary endpoints: PFS, ORR, and adverse events (AEs).

Key results

  • At a median follow-up of 16.6 months, median OS:
    • 16.6 months with DT+CT. 
    • 14.1 months with DT.
      • Estimated HR, 0.88 (log-rank P=.46).
  • PFS:
    • 7.7 months with DT+CT.
    • 3.2 months with DT.
      • Stratified HR, 0.67 (log-rank P=.0035).
  • ORR was significantly improved with DT+CT vs DT.
  • Blood-based tumor molecular burden 
  • Grade ≥3 AEs in:
    • 82% with DT+CT.
    • 70% with DT.

Funding

  • Canadian Cancer Society Research Institute.
  • Astra Zeneca.

Expert commentary

  • “We need to better understand the biology behind sensitivity and resistance to various immunotherapeutic drugs to better narrow therapies to our patients,” says Scott Gettinger, professor of internal medicine at the Yale Cancer Center.