Once vs Twice-Daily Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer



Title: Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial

Faivre-Finn, C et al.


 

What You Need to Know:

According to results of a phase 3 study (CONVERT trial), no difference in survival outcomes was observed when concurrent chemoradiotherapy was dosed once daily versus twice daily in patients with limited-stage small-cell lung cancer.

Trial Design:

  • Open-label, randomized, phase 3 superiority study aimed to establish a standard chemoradiotherapy regimen for patients with cytologically or histologically confirmed limited-stage small-cell lung cancer
  • 547 patients were randomly assigned to receive “45 Gy radiotherapy in 30 twice-daily fractions of 1.5 Gy over 19 days, or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin-etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups)”
  • Primary endpoint: overall survival (time from randomization to death by any cause); utilized a modified intention-to-treat analysis
  • Secondary endpoints: compliance, acute toxicity, late toxicity, local and metastatic progression-free survival
  • “A 12% higher overall survival at 2 years in the once-daily group versus the twice-daily group was considered to be clinically significant to show superiority of the once-daily regimen”

Key Outcomes:

  • A total of 273 patients were randomized to the once-daily group and 274 patients were randomized to the twice-daily group
  • Median overall survival at 45 months: 30 months (95% CI: 24, 34) for patients in the twice-daily group vs 25 (95% CI: 21, 31) months for patients in the once-daily group (HR for death in the once-daily group: 1.18; 95% CI: 0.95, 1.45; P=0.14)
  • 2-year overall survival rate: 56% (95% CI: 50, 62) for patients in the twice-daily group vs 51% (95% CI: 45, 57) for patients in the once-daily group (absolute difference: 5.3%; 95% CI: -3.2, 13.7)
  • Neutropenia was the most common grade 3-4 adverse event reported; experienced by 74% of patients in the twice-daily group vs 65% of patients in the once-daily group
  • Treatment groups had similar rates of toxicities, however significantly more patients in the twice-daily group experienced grade 4 neutropenia compared to patients in the once-daily group (49% vs 38%, respectively; P=0.05)
  • No difference in the rates of grade 3-4 oesophagitis or radiation pneumonitis observed between the two treatment groups
  • Death due to treatment-related causes: 3 patients in the twice-daily group vs 8 patients in the once-daily group