WA, USA, 14Millennium Pharmaceuticals Inc., a wholly owned subsidiary of .... Kyowa Hakka Kirin, Seattle Genetics, Inc., Spectrum Pharmaceuticals, Millennium.
Patient-reported outcomes and quality of life in patients with cutaneous T cell lymphoma: results from the Phase 3 ALCANZA study H Miles Prince,1 Reinhard Dummer,2 Sean Whittaker,3 Steven M Horwitz,4 Madeleine Duvic,5 Julia Scarisbrick,6 Pietro Quaglino,7 Pier Luigi Zinzani,8 Pascal Wolter,9 Jose A Sanches,10 Pablo L Ortiz-Romero,11 Oleg E Akilov,12 Larisa Geskin,12 Auris Huen,5 Yinghui Wang,13 Maria Corinna Palanca--Wessels,13 Akshara Richhariya,13 Joseph Feliciano,13 Yanyan Zhu,14 Hui Min Lin,14 Yi Liu,14 Meredith Little,14 Erin Zagadailov,14 Mehul R Dalal,14 Youn H Kim15 University of Melbourne, Melbourne, Australia, 2University Hospital Zürich, Zürich, Switzerland, 3Guys and St Thomas NHS Foundation Trust, London, United Kingdom, 4Memorial Sloan Kettering Cancer Center, New York, NY, USA, 5University of Texas MD Anderson Cancer Center, Houston, TX, USA, 6University Hospital Birmingham, Birmingham, United Kingdom,7University of Turin, Turin, Italy, 8University of Bologna, Bologna, Italy, 9University Hospitals Leuven, Leuven, Belgium, 10University of São Paulo Medical School, São Paulo, Brazil, 11University Hospital 12 de Octubre, Madrid, Spain, 12University of Pittsburgh, Pittsburgh, PA, USA, 13Seattle Genetics, Inc., Bothell, WA, USA, 14Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA, 15Stanford University School of Medicine, Stanford, CA, USA 1
Background
Table 1. Patient baseline characteristics in ALCANZA
Baseline characteristics
Brentuximab vedotin (n=64)
Methotrexate or bexarotene (n=64)
Median age, years (range)
62 (22–83)
59 (22–83)
Male gender, n (%)
33 (52)
37 (58)
ECOG PS 0–1, n (%)
61 (95)
62 (97)
MF,* n (%)
48 (75)
49 (77)
Early stage (IA–IIA)
15 (31)
18 (37)
Advanced stage (IIB–IVB†)
32 (67)
30 (61)
16 (25)
15 (23)
Skin only
9 (56)
11 (73)
Extracutaneous disease
7 (44)
4 (27)
Total number of prior therapies, median (range)
4.0 (0–13)
3.5 (1–15)
Number of prior systemic therapies, median (range)
2.0 (0–11)
2.0 (1–8)
FACT-G total
71.2 (17.0)
73.1 (17.9)
FACT-G physical wellbeing
19.8 (6.3)
20.0 (6.3)
FACT-G social/family wellbeing
20.3 (6.2)
22.0 (6.0)
FACT-G emotional wellbeing
15.4 (4.5)
15.4 (5.3)
FACT-G functional wellbeing
15.6 (6.1)
15.9 (7.1)
Skindex-29 total
49.8 (22.0)
47.9 (20.0)
pcALCL, n (%)
Skindex-29 symptoms domain
57.5 (23.4)
55.1 (21.1)
Skindex-29 emotions domain
49.5 (22.4)
45.8 (22.9)
Skindex-29 functioning domain
42.3 (25.9)
40.4 (25.0)
EQ-5D-3L visual analog scale
0.76 (0.20)
0.73 (0.22)
Methotrexate: 5–50 mg PO, weekly or Bexarotene: 300 mg/m2 (target dose) PO, daily
Exclusion: • Progression on both prior methotrexate and bexarotene
• Mean change from baseline to end of treatment in FACT-G total scores were similar in brentuximab vedotin and physician’s choice arms (0.15 vs –2.29, respectively). • No substantial differences in QoL were observed on EQ-5D US time tradeoff, the UK time tradeoff, or visual analog scores: mean changes from baseline to end of treatment were 0.02, 0.03, 0.8, respectively, in the brentuximab vedotin arm and –0.02, –0.04, –2.0, respectively, in the physician’s choice arm. • No differences in FACT-G and EQ-5D scores were seen between patients with and without peripheral neuropathy.
Physician's choice 100
80
80 Mean score (SD)
100
60 40 20
40 20 0
–20
–20 C2D1
C4D1
C6D1
C8D1 C10D1 Cycle/day
C12D1
C14D1
C16D1
Brentuximab vedotin Physician's choice
Symptom domain
60
0 Baseline
Baseline
EOT
C2D1
C4D1
C6D1
58 49
52 33
42 28
Objectives
61 57
57 49
51 33
42 28
39 16
36 15
27 10
27 6
22 4
46 41
Brentuximab vedotin Physician's choice
C12D1
C14D1
C16D1
EOT
61 57
100
80
80
60 40 20
27 10
27 6
22 4
46 41
C12D1
C14D1
C16D1
EOT
27 10
27 6
22 4
46 41
40 20 0
–20
–20 C2D1
C4D1
C6D1
C8D1 C10D1 Cycle/day
37 15
60
0 Baseline
39 16
Functional domain
100
C12D1
C14D1
C16D1
EOT
Number of patients Brentuximab vedotin Physician's choice
C8D1 C10D1 Cycle/day
Number of patients
Emotional domain
• Methotrexate or bexarotene was managed as a standard of care, targeting maximum tolerated effective dose
• Key ALCANZA QoL secondary endpoint: Symptom domain of Skindex-29. • Other ALCANZA QoL secondary endpoints: Emotion and functioning domains of Skindex-29, and FACT-G Questionnaire. • Exploratory ALCANZA QoL endpoint: EQ-5D.
FACT-G and EQ-5D
Number of patients
Mean score (SD)
*Within 28 days of randomization
30 days after last dose of study drug
•
Brentuximab vedotin
Total score
Posttreatment follow-up Every 12 weeks for 2 years and then every 6 months thereafter
•
Mean score (SD)
Randomization
Brentuximab vedotin: 1.8 mg/kg IV, every 3 weeks
EOT visit
•
Figure 2. Mean Skindex-29 total and domain scores over time
Screening*
Up to 48 weeks (16 x 21-day cycles)
•
*One patient in each arm had incomplete staging data and are not included; †Stage IVB MF, n=7 in brentuximab arm vs n=0 in methotrexate/ bexarotene arm
Figure 1. Key eligibility criteria and study design of ALCANZA
Inclusion: • Diagnosis of CD30-positive MF or pcALCL – ≥10% CD30-positive on either neoplastic cells or lymphoid infiltrate by central review of ≥1 biopsy (≥2 required for MF) • MF patients with ≥1 prior systemic therapy • pcALCL patients with prior radiotherapy or ≥1 prior systemic therapy
•
Mean baseline scores (SD)
Mean score (SD)
• CTCL, a heterogeneous group of T-cell lymphomas primarily involving the skin, is a chronic, incurable disease, which, in addition to being itchy and painful, is a highly visible cancer that is often disfiguring.1 Since the symptom burden can be highly detrimental to patients’ well---being, maintaining QoL is a key goal of patient management. • Treatment options are determined by disease subtype and stage, with skin-directed therapy used to treat early-stage disease, and systemic therapies or SCT for the treatment of more generalized or advanced disease.2 Many patients, however, relapse or become refractory to front-line therapy. • In two phase 2, investigator-sponsored trials, brentuximab vedotin, a CD30-targeting antibody-drug conjugate, showed significant clinical activity with an acceptable safety profile in CTCL (ORR: 54% in MF and 100% in pcALCL;3 70% in MF/Sézary syndrome4). • Recently, brentuximab vedotin, a CD30-targeting antibody-drug conjugate, has been evaluated in ALCANZA (NCT01578499), an international, open-label, multicenter trial and the first reported randomized phase 3 trial to evaluate a new systemic agent versus standard of care in CD30-positive MF or pcALCL.5 • In ALCANZA, brentuximab vedotin was far superior to physician’s choice (methotrexate or bexarotene), demonstrating improvement in the primary endpoint of ORR4 (56% vs 13%; p
