Treatment of soft tissue sarcoma (STS) with long-term systemic therapy can be limited by cumulative toxicity. Treatment with T for prolonged courses without the cumulative toxicity has been previously described from clinical trials. Here we report the efficacy and safety for patients (pts) treated long term (≥ 6 months) in a real world setting in the T Expanded Access Program from 2005-2010.
In this retrospective analysis of pts with pre-treated, relapsed/refractory STS of multiple histologies treated ≥6 mo with T (1.5 mg/m2 iv q3wk), we compared pts treated 6-12 mo and >12 mo.
Of 1803 pts, 401 (21.6%) remained on treatment ≥6 mos; 268 (14.5%) for 6-12 mo and 133 (7.2%) >12 mo. Demographics did not differ. Leiomyosarcoma or liposarcoma were the most common histologies. The mOS (mo) was 18.1 and 47.0, ORR was 7.8% and 6.8%, and clinical benefit rate (CR+PR+SD) (95%CI) was 47.4% (41.3;53.6) and 38.3% (30.1;47.2) in the 6-12 mo and >12 mo groups, respectively. The incidence of adverse events (AE)s and serious adverse events (SAE)s were similar in both groups (Table). The most common grade 3/4 AEs occurring in ≥ 5% were neutropenia, thrombocytopenia, anemia, ALT/AST increase, fatigue and nausea. A majority received dose reduction or delay; the primary reason for treatment discontinuation was disease progression. The longest observed duration of treatment was 55 mo (64 cycles; synovial sarcoma) and 54 mo (73 cycles; uterine leiomyosarcoma).Table:
1497P Safety and Efficacy
|6-12 Months||>12 Months|
|(N = 268)||(N = 133)|
|Median Treatment Duration (mo), range||8.4(6; 12)||16.3 (12; 55)|
|Complete response, n (%)||1 (0.4)||3 (2.3)|
|Partial response, n (%)||20 (7.5)||6 (4.5)|
|Stable disease, n (%)||106 (39.6)||42 (31.6)|
|Progressive disease, n (%)||20 (7.5)||12 (9.0)|
|Not available, n (%)||121 (45.1)||70 (52.6)|
|Treatment-emergent adverse events (TEAEs)||225 (84.0)||119 (89.5)|
|Serious TEAEs||88 (32.9)||47 (35.3)|
|Treatment discontinued||255(95.1)||103 (77.4)|
|Due to disease progression||192(71.6)||72 (54.1)|
|Due to adverse event||10 (3.7)||2 (1.5)|
|Patients with cycle delay||154 (57.5)||82 (61.7)|
|Patients with dose reduction||172 (64.2)||104 (78.2)|
T can be safely administered and well tolerated in pts who receive a prolonged duration (≥6 mo) of therapy. Improved mOS may be achieved in pts who experience prolonged disease stabilization following T but adjustments in dose or schedule is frequently required.
Clinical trial identification
Legal entity responsible for the study
Janssen Research & Development, LLC
Janssen Research & Development, LLC
S. Schuetze: Honorarium for Janssen ad hoc scientific advisory board to me. Research funding to institution (University of Michigan) from Janssen. S. Patel: Consultant to: Janssen, Eisai, Novartis, CytRx, Epizyme, Bayer, Eli Lilly Grants for clinical trial from: Janssen, Eisai, Morphotek. R. Maki: Consulting or advisory role: SARC, ASCO, AADX, ARCUS, Bayer, GSAI, GEM, Novartis, GSK, Immune Design, Janssen, Kyropharm, Lilly Tracon and Presage Research Funding and Travel, Accommodations, Expenses: Tracon, Immune Design, Lilly, and SARC. R.L. Jones: Consultant for: Adaptimmune, Blueprint, Eisai, Epizyme, Daichii, Deciphera, Janssen Scientific Affairs, LLC, Immunedesign, Lilly, Merck, Pharmamar. C.R. Shin, R. Knoblauch, G. Wang, M. Smith: Employee of Janssen and own stock in Johnson & Johnson. G.D.S. Demetri: Consulting: Novartis, Janssen, PharmaMar, Daiichi-Sankyo, Adaptimmune, Eisai Patent licensed to Novartis from Dana-Farber with royalty paid to Dana-Farber Research support to Dana-Farber: Novartis, Janssen. All other authors have declared no conflicts of interest.