ASH 2018 | Secondary analysis of the phase III GOYA trial: CHOP6 versus CHOP8 for first-line DLBCL

On Monday 3 December 2018, during the 60^th Annual Meeting of the American Society of Hematology (ASH), San Diego, CA, Laurie Sehn from British Columbia Cancer Agency, Vancouver, CA, presented the results of the phase III trial GOYA (Abstract #783; Oral Session #626).

GOYA (NCT01287741) was an international, open-label, randomized, phase III trial that compared the efficacy and safety of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) to obinutuzumab (G) plus CHOP in previously untreated patients diffuse large B-cell lymphoma (DLBCL) patients. In the primary analysis of the GOYA trial, there was no significant difference in the three-year PFS of patients receiving R-CHOP to those receiving G-CHOP. In this current secondary analysis, the assessed endpoints were investigator-assessed (INV) progression-free survival (PFS), and overall survival (OS) in patients receiving six cycles of CHOP (CHOP6) versus eight cycles of CHOP (CHOP8). Secondary endpoint was safety of CHOP6 versus CHOP8.

Study design

• N = 1418 previously untreated DLBCL patients, aged ≥ 18 with International Prognostic Index (IPI) ≥ 2 or IPI = 1 due to age alone or IPI = 0 with bulky disease (one lesion ≥ 7.5cm), Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, and ≥ 1 bi-dimensionally measurable lesion
• These patients were 1:1 randomized according to planned number of CHOP cycles, IPI, and geographic region to either:
  • G-CHOP (n = 706) or;
  • R-CHOP (n = 712)
• Dosing:
  • G-CHOP: 1000 mg of G on Day 1,8, and 15 of cycle 1 and on Day 1 of cycles 2−8. CHOP for 6 or 8 cycles every 21 days
  • R-CHOP: 375 mg/m² of R on Day 1 on cycles 1−8. CHOP for 6 or 8 cycles every 21 days
  • The number of CHOP cycles (6 or 8) was pre-selected at each site prior to trial opening
    • CHOP6: n = 526 patients
    • CHOP8: n = 186 patients
  • Data cut-off: January 31, 2018
  • Median follow-up: 3.9 years

Results

• Median follow-up: 29 months
• GOYA primary analysis results:
  • INV PFS (R-CHOP [n = 712] vs G-CHOP [n = 706]):
  • One-year PFS: 79.8% vs 6%
  • Two-year PFS: 71.3% vs 4%
  • Three-year PFS: 66.9% vs 6%
    • Comparison: HR = 0.92; 95% CI (0.76−1.11); P = 0.3868
  • Current exploratory analysis results:
    • INV PFS (CHOP6 [n = 526] vs CHOP8 [n = 186]):
    • Three-year PFS: 68.7% vs 8%
      • Comparison: HR = 0.92; 95% CI (0.69−1.23)
    • INV OS (CHOP6 [n = 526] vs CHOP8 [n = 186]):
      • Three-year OS: 83.2% vs 2%
        • Comparison: HR = 0.65; 95% CI (0.46−0.91)
      • Subgroup analysis according to initial bulky disease, high IPI, ABC subtype, or partial response on interim computerized tomography did not identify any group that benefits (PFS) from 8 versus 6 CHOP cycles

Safety

• Total adverse events (AEs) were lower in the CHOP6 (42.7%; n = 461) arm than the CHOP8 (65.3%; n = 144)
• Grade 3−5 AEs were lower in the CHOP6 (17.8%; n = 461) arm than the CHOP8 (38.9%; n = 144)
• Serious AEs were lower in the CHOP6 (12.2%; n = 461) arm than the CHOP8 (20.1%; n = 144)

Conclusions

• No additional clinical benefit was observed with 8 versus 6 cycles of CHOP in combination with rituximab
• Subgroup analysis did not identify any clinical or biological subgroup that benefited from 8 CHOP cycles
• Grade 3−5 AEs and all grade infections were markedly higher in patients receiving 8 CHOP cycles, compared to those receiving 6 CHOP cycles
• According to the investigators, six cycles of CHOP (3-weekly) in combination with rituximab should be considered standard of care for patients with advanced-stage DLBCL