OBJECTIVES: A systematic review was conducted to identify available evidence on the clinical efficacy, effectiveness, and safety of frontline treatments in PTCL.

METHODS: MEDLINE, Embase, Cochrane, DARE, and grey literature sources were searched for studies reporting OS, PFS, response, safety, and HRQoL data. Studies had to be published in English and were not limited by intervention, geography, or publication year.

RESULTS: Prespecified PICOS criteria were used to screen, 557 titles/abstracts and 120 full texts with 47 studies reporting data of interest; seven RCTs and 40 non-RCTs. Most studies investigated CHOP or ‘CHOP-like’ regimens, with CHOP combination regimens showing similar efficacy/effectiveness vs. CHOP alone; only brentuximab vedotin plus cyclophosphamide, doxorubicin and prednisone (A+CHP) showed a significantly higher OS and PFS versus CHOP. The 2-year OS rates ranged from 50% on CHOP to 80.8% with A+CHP; 2-year PFS rates were higher for A+CHP vs. CHOP+everolimus (61.4% vs 33% respectively) in the overall PTCL population. The highest 2-year OS and 3-year PFS rates reported across the included studies were in the ALCL ALK- (OS and PFS: 100%), ALCL ALK+ (OS: 50% and PFS:100%), and AITL (OS: 88% and PFS: 55%) subtypes, respectively. Response to CHOP was similar in all PTCL subtypes with the highest ORR reported for ALCL ALK+ patients (84%). ORR were not significantly different across frontline treatments compared with CHOP. Safety data were limited and heterogeneous; with no data on treatment-related AEs. No HRQoL data was identified.

CONCLUSIONS: Available evidence indicates that except A+CHP, no other regimen showed a statistically significant benefit over CHOP in terms of OS and PFS - in the overall PTCL population and in some subtypes. There is limited efficacy/effectiveness data by PTCL subtypes, and limited safety and HRQoL data. Future studies should explore the effectiveness, safety, and HRQoL impact of frontline treatments especially in the rare PTCL subtypes.