Gemcitabine-based chemotherapy is not superior to CHOP for naïve PTCL patients

In May 2018, Mary Gleeson from The Royal Marsden NHS Foundation Trust, London and Surrey, UK, and colleagues, published in The Lancet Haematology results from the CHEMO-T (NCT01719835) randomized, open-label, multicenter, phase II trial on the use of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) versus gemcitabine, cisplatin, and methylprednisolone (GEM-P) in previously-untreated patients with peripheral T-cell lymphoma (PTCL).

PTCL is a rare heterogeneous subtype of non-Hodgkin lymphoma with no current consensus on the best first-line chemotherapy regimen for previously-untreated patients. Although, CHOP together with autologous stem cell transplantation is widely used in PTCL, for most patients the outcomes are poor. CHOP in combination with etoposide (CHOEP) has also been investigated for PTCL but with no benefit in patients’ overall survival (OS). Thus, there is an unmet medical need for a superior first-line regimen for PTCL.

Gemcitabine–a nucleoside analog–used as chemotherapy in various carcinomas, is not affected by multidrug resistance 1-P glycoprotein (MDR 1-Pgp) gene which is overexpressed in some PTCL cases and has shown promising activity in the relapsed/refractory PTCL setting. In line with these results and the poor CHOP outcomes in PTCL, this phase II trial sought to comparatively investigate the efficiency of GEM-P and CHOP in naïve PTCL patients. The primary endpoint was the proportion of patients with a CT-based complete response (CR) or unconfirmed complete response (CRu) on trial completion and safety was a secondary endpoint.

Key findings

• Total patients (N = 87) from 47 hospitals (46 in the UK and 1 in Australia)
• Randomly assigned to CHOP: n = 43
• Randomly assigned to GEM-P: n = 44
• CHOP every 21 days for six cycles: intravenous cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², and vincristine 1.4 mg/m² (maximum 2 mg) on Day 1, and oral prednisolone 100 mg on Days 1–5
• GEM-P every 28 days for four cycles: intravenous gemcitabine 1000 mg/m² on Days 1, 8, and 15, cisplatin 100 mg/m² on Day 15, and oral or intravenous methylprednisolone 1000 mg on Days 1–5
• At median follow-up of 27.4 months, patients achieving CR/CRu:
  • CHOP arm 62% vs GEM-P arm 46% (odds ratio [OR] 0·52; 95% CI [0.21–1.31]; P = 0·164)
• No difference in the number of patients achieving CR or CRu with GEM-P or CHOP

Safety

• Most common grade ≥ 3 adverse events in both groups:
• Neutropenia: 40% CHOP arm vs 20% GEM-P arm,
• Thrombocytopenia: 10% CHOP arm vs 30% GEM-P arm
• Febrile neutropenia: 29% CHOP arm vs 7% GEM-P arm
• Two patients in the GEM-P group (5%) died from lung infection

The results of this trial indicate that GEM-P is not a more effective regimen than CHOP for previously untreated PTCL patients. Due to the suboptimum CHOP outcomes and the failure of GEM-P in naïve PTCL patients, the authors stated that ‘optimizing therapy for newly-diagnosed patients remains an important unmet medical need’.