Treatment options for pts with advanced STS are limited. STS, like other proliferating malignancies, are dependent on the formation of new blood vessels to support their growth, invasion and metastasis. Growth Modulation Index (GMI) has been demonstrated as a relevant endpoint to assess clinical in patients with advanced STS. There are no data related to GMI in STS patients treated with anti-VEGFR targeted therapy.
Pts with metastatic STSs diagnosed between 1990 and 2013 and documented in the prospectively maintained database of the French Sarcoma Group who have received at least one TKI during their treatment were analysed. GMI, defined as the ratio of the Time To Progression (TTP2) under the TKI/TTP under the previous line of treatment (TTP1) was calculated.
209 pts (102 male) were included in this study. Median age was 50 (11-83). 234 lines of TKI were administrated. The drugs used were: Pazopanib (77, 33%), Sorafenib (70, 30%), Sunitinib (45, 19%), Regorafenib (30, 13%), Others (12, 5%). The most frequent histology subtypes were: leiomyosarcoma (64, 30.6%), undifferentiated sarcoma (28, 13.4%), synovialosarcoma (20, 9.6%), desmoplastic round cell tumor (14, 6.7%) and angiosarcoma (11, 5.3%). Median of previous lines was 2 (0 – 4). Median TTP under TKI was 4.1 months (0 – 131.1). GMI was available for 201 pts. Median GMI was 0.76 (0.02 - 12.49). GMI was ≥ 1 in 87 (41.6%) pts and ≥ 1.3 in 65 (31.1%) pts. 17 pts received 2 consecutive lines of TKI. For these pts, median GMI (TTP under TKI2/TTP under TKI1) was 1 (0.12 – 8.77). Seven (41.2%) had a GMI ≥ 1.3.
Targeting VEGFR was associated with significant clinical benefit (GMI ≥ 1.3) in about one third of STS pts. Up to 41% of patients progressing on a TKI experienced clinical benefit with another TKI suggesting the lack of absolute cross-resistance between TKI.
Clinical trial identification
Legal entity responsible for the study
French Sarcoma Group
All authors have declared no conflicts of interest.