PHASE 3 ALCANZA STUDY OF BRENTUXIMAB VEDOTIN (BV) OR PHYSICIAN'S CHOICE (PC) OF METHOTREXATE (MTX) OR BEXAROTENE (BEX) IN CD30-POSITIVE CUTANEOUS T-CELL LYMPHOMA (CTCL):NUMBER NEEDED TO TREAT ANALYSIS
Author(s): ,
Erin Zagadailov
Affiliations:
Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge,United States
,
H. Miles Prince
Affiliations:
The University of Melbourne,Victoria,Australia
,
Sean Whittaker
Affiliations:
Guys and St Thomas NHS Foundation Trust,London,United Kingdom
,
Steven Horwitz
Affiliations:
Memorial Sloan Kettering Cancer Center,New York,United States
,
Madeleine Duvic
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Youn Kim
Affiliations:
Stanford University School of Medicine and Stanford Cancer Institute,California,United States
,
Reinhard Dummer
Affiliations:
University Hospital Zürich,Zürich,Switzerland
,
Julia Scarisbrick
Affiliations:
University Hospital Birmingham,Birmingham,United Kingdom
,
Pietro Quaglino
Affiliations:
University of Turin,Turin,Italy
,
Pier Luigi Zinzani
Affiliations:
University of Bologna,Bologna,Italy
,
Pascal Wolter
Affiliations:
University Hospitals Leuven,Leuven,Belgium
,
Larisa Geskin
Affiliations:
Columbia University,New York,United States
,
Joseph Feliciano
Affiliations:
Seattle Genetics, Inc.,Bothell,United States
,
Yinghui Wang
Affiliations:
Seattle Genetics, Inc.,Bothell,United States
,
Maria Corinna Palanca-Wessels
Affiliations:
Seattle Genetics, Inc.,Bothell,United States
,
Ashish Gautam
Affiliations:
Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge,United States
,
Yanyan Zhu
Affiliations:
Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge,United States
,
Hui-Min Lin
Affiliations:
Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge,United States
,
Yi Liu
Affiliations:
Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge,United States
,
Meredith Little
Affiliations:
Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge,United States
Mehul R. Dalal
Affiliations:
Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge,United States
EHA Library. R. Dalal M. 06/24/17; 181924; P637
Mehul R. Dalal
Mehul R. Dalal
Contributions
Abstract

Abstract: P637

Type: Poster Presentation

Presentation during EHA22: On Saturday, June 24, 2017 from 17:30 - 19:00

Location: Poster area (Hall 7)

Background
CTCL is a generally incurable, relapsing disease associated with a significant symptom burden, including disfiguring lesions, debilitating pruritus and frequent skin infections. ALCANZA is a Phase 3 study of BV vs PC (MTX or Bex) for the treatment of CD30-positive (CD30+) CTCL (NCT01578499). BV was associated with significantly improved rate of objective response lasting ≥4 months (ORR4; 56% vs 13%; p<0.0001), longer median progression-free survival (PFS; 16.7 vs 3.5 months; p<0.0001), and decreased symptom burden measured by Skindex-29 ( 27.96 vs -8.62; p<0.0001), compared with PC. BV’s safety profile was consistent with previous reports, with all-grade and grade 3 peripheral neuropathy of 67% and 9%, respectively. Number needed to treat (NNT), defined as the number of patients (pts) that need to be treated to prevent one outcome event relative to the comparator therapy, is an effective method to assess the benefit-risk of BV in a clinically relevant manner. NNT values of 3–28 have been previously reported, at various time points, in hematologic malignancies (multiple myeloma, B-cell non-Hodgkin lymphoma) to prevent one disease progression event or death. Data from the Phase 3 AETHERA study demonstrated that, at various time points, and dependent on risk group, one in 3–8 Hodgkin lymphoma pts treated with BV consolidation therapy post-autologous stem cell transplant will benefit by avoiding disease progression/death, compared with placebo.

Aims
To determine the NNT with BV to avoid one additional event of disease progression or death compared with PC in the ALCANZA trial.

Methods
The NNT with BV was calculated as the inverse of the absolute risk reduction (ARR); ARR was the PFS event rate per independent review facility (IRF) assessment in the PC arm minus the event rate in the BV arm. PFS was defined as the time from randomization until progressive disease/death due to any cause, counting all events despite two or more missed visits or starting of subsequent anticancer therapy (European Medicines Agency [EMA] criteria). ALCANZA recruited adults (≥18 years) with previously treated CD30+ mycosis fungoides or primary cutaneous anaplastic large cell lymphoma. Pts were randomized 1:1 to receive BV 1.8 mg/kg IV, once every 3 weeks, for up to 16 three-week cycles, or PC of MTX 5–50 mg PO, once weekly, or Bex 300 mg/m² (target dose) PO, once daily, for up to 48 weeks. All pts gave informed consent.

Results
The intent-to-treat (ITT) population comprised 128 pts (median age 60 yrs [range 22–83]; 55% male) who received BV (n=64) or PC (n=64). Fewer PFS events per IRF assessment per EMA criteria were experienced by pts in the BV arm vs PC arm (Table). The NNT with BV to prevent a disease progression/death ranged from 2.00 (95% CI 1.59, 3) to 3.76 pts (95% CI 2.5, 8.44) over 24 months (Table). At 24 months, the NNT to prevent a disease progression/death was 3.37 pts (95% CI 2.26, 7.67).

Table: NNT analysis per IRF assessment of PFS in the ALCANZA ITT population
Month
Number of PFS events per IRF analysis
NNT
95% CI
BV (n=64)
PC (n=64)
3
7
24
3.76
2.5, 8.44
6
11
42
2.06
1.63, 3.13
9
15
47
2.00
1.59, 3
12
19
47
2.29
1.75, 3.73
15
21
47
2.46
1.84, 4.24
18
29
47
3.56
2.33, 8.99
21
29
48
3.37
2.25, 7.83
24
31
50
3.37
2.26, 7.67

Conclusion
ALCANZA data suggest that, at various time points, one in every 2–4 pts treated with BV will benefit by avoiding disease progression/death. This further demonstrates BV’s clinical benefit in CD30+ CTCL pts requiring systemic therapy. This is, to our knowledge, the first report of an NNT analysis for a treatment in the CTCL setting.

Session topic: 19. Indolent Non-Hodgkin lymphoma - Clinical

Keyword(s): Cutaneous T-cell lymphoma, CD30

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