Table 1 Overview of the reported efficacy data from prospective and retrospective clinical trials of pazopanib monotherapy in advanced soft tissue sarcoma
Study | Prospective | Retrospective | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Â | Sleifjer (2009)18 | Van der Graaf (2012)6 | Frezza (2014)72 | Benson (2016)26 | Samuels (2017)28 | Martin-Broto (2019)45 | Maruzzo (2015)43 | Stacchiotti (2018)73 | Frezza (2018)74 | Gelderblom (2017)27 | Jones (2017)75 | Kollar (2016)76 | Menegaz (2017)77 | Nakamura (2016)78 | Nakano (2015)79 | Stacchiotti (2014)44 | Yoo (2015)80 |
Design | Non-comparative phase II | Double blind, placebo-controlled, phase III | Subgroups from phII and III trials + EAP data | Subgroups from phII and III trials | Single arm, multicentre US phase II | Single arm, multicentre European phase II | Single centre case series | Int’l multicentre case series | Int’l multicentre case series | Intl’ multicentre case series based on EAP | Int’l case series | European multicentre case series, inc phase II/III | UK centre case series | Japanese multicentre case series | Japanese centre case series | Italian multicentre series | Korean centre series |
N | 142 | 369 | 9 | 44 | 41 | 36 | 13 | 30 | 18 | 211 | 8 | 52 | 29 | 156 | 47 | 6 | 43 |
Subtypes | LMS, SS, LPS, ‘Other’ | Mixed (LPS excluded | DSRCT | Uterine sarcoma (89 % LMS) | LPS (int/high grade) | SFT | SFT | ASPS | Epithelioid sarcoma | Mixed | Chondro-sarcoma | Vascular sarcomas | DSRCT | Mixed | Mixed | SFT | Mixed |
Eligibility | <3 prior lines | 1–3 prev lines | ≥2nd line | ≥2nd line | Any line | Any line | 1st line | Any line | Any line | 1–3 prev lines | Any line | Any line | Any line | Any line | Any line | Any line | ≥2nd line |
Best response: CR or PR | 6% | 6% | 22% | 11% | 2% | 6% | 8% | 27% | 0% | 7% | 0% | 23% | 7% | 8% | 11% | 0% | 16% |
SD | NR | 67% | 56% | 57% | 42% | 60% | 62% | 57% | 50% | 18% | 75% | 21% | 55% | 47% | NR | 50% | 42% |
PrD | NR | 24% | 22% | 32% | 66% | 34% | 15% | 13% | 50% | 41% | 25% | 50% | 38% | 24% | NR | 50% | 37% |
12wPFR | LMS:44% SS:49% LPS:26% Other:39% | 60%a | 67% | 50% | 68% | NR | 62% | 59% | 50% | 50% | 75% | AS:45%a EHE:60%a | 62% | 60%a | 60%a | 50%a | NR |
Median PFS (months) | LMS:3.0 SS:5.4 LPS:2.7 Other:3.0 | 4.6 (vs. 1.6 in placebo arm) | 9.2 | 3 | 4.4 | 5.6 | 4.7 | 13.6 | 3 | 3 | NA | AS: 3.0 EHE: 26.3 | 5.6 | 3.6 | 4.3 | 3 | 5 |
Median OS (months) | LMS:11.8 SS:10.3 LPS:6.6 Other:10.0 | 12.5 (vs. 10.7 in placebo arm) | 15.4 | 17.5 | 12.6 | Not reached | 13.3 | Not reached | 14 | 11.1 | NR | AS: 9.9 EHE 26.3 | 15.7 | 11.2 | 9.6 | NR | 8.2 |
Comments | Favorable PFS and OS vs. historical control in LMS, SS and Other subgroups - | Drug licensed in pre-treated non-adipocytic STS based on evidence of PFS benefit |  | In PALETTE trial, significantly longer PFS and OS with pazopanib vs. placebo | LPS subtypes: 66% DDLPS, 29% MLPS, 5% PleoLPS | Response by Choi criteria: 51% PR 26% SD 23% PrD |  | Median follow-up 19 months | Authors conclude limited activity in ES |  | 5/8 Convent-ional CS 1/8 ESMC 1/8 MC 1/8 clear cell | Equivalent ORR in cutaneous vs. non-cutaneous or 1° vs. 2° AS |  | NB 33/156 (21%) LPS | Trend toward better PFS in PALETTE eligible subtypes (HR 0.56, 95% CI 0.25–1.23, p = 0.15) |  |  |
