WCLC 2019 – Durvalumab plus chemotherapy significantly improves survival in patients with extensive-stage SCLC


  • Cristina Ferrario — Agenzia Zoe
  • Univadis
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Takeaway

  • In the first-line treatment of extensive-stage small-cell lung cancer (ES-SCLC), the addition of durvalumab (D) to the standard chemotherapy based on etoposide-platinum (EP) significantly prolongs overall survival (OS), with a 27% reduction in the risk of death.
  • No new safety signals emerged in the combination regimen.

Why this matters

  • Patients with ES-SCLC treated with etoposide-platinum typically relapse within 6 months and the median OS is approximately 10 months.
  • Limited alternatives have been available over three decades and new treatments are needed to prolong survival.

Study design

  • The open-label, multicentre and phase 3 CASPIAN study, evaluates durvalumab (D), ± tremelimumab, in combination with EP as first-line treatment of ES-SCLC.
  • Results from a planned interim analysis on durvalumab + EP (D+EP) versus EP are reported hereafter.
  • Patients with previously untreated ES-SCLC were randomised to durvalumab 1500 mg + EP q3w (n=268) or EP q3w (n=269).
  • In the immunotherapy group, patients were treated with up to 4 cycles of EP followed by maintenance durvalumab until progression.
  • In the chemotherapy group, up to 6 cycles of EP and optional prophylactic cranial irradiation (PCI) were administered, as by investigator’s discretion.
  • Investigators were allowed to choose the platinum regimen (carboplatin or cisplatin), reflecting current clinical practice.
  • The primary endpoint was OS; secondary endpoints included progression-free survival (PFS) and objective response rate (ORR).

Key results

  • OS was significantly higher in D+EP group compared to EP group (HR 0.73; p=0.0047), with a median OS of 13.0 versus 10.3 months was observed, respectively.
  • At 18 months, 33.9% of patients treated with D+EP and 24.7% with EP were alive.
  • 12-month PFS rate was 17.5% versus 4.7% with D+EP and EP, respectively; confirmed ORR (investigator-assessed per RECIST v1.1) was 67.9% versus 57.6%.
  • Safety data were similar in the two groups with 61.5% and 62.4% of patients reporting grade 3-4 adverse events (AEs) in D+EP and EP group, respectively.

Funding

  • AstraZeneca.

Expert commentary

“CASPIAN study confirmed the role of immune checkpoint inhibitors in ES-SCLC. Given the efficacy of immunotherapy in SCLC is observed in a minority of patients, studies on predictive biomarkers are warranted to identify patients more likely to benefit”. Ahn MJ. Professor, Division of Hematology-Oncology, Department of Medicine. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.