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 | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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) | ||||||
CR complete response, PR partial response, SD stable disease, PrD progressive disease, 12wPFR 12 week progression-free rate, PFS progression-free survival, OS overall survival, LMS leiomyosarcoma, SS synovial sarcoma, LPS liposarcoma, DSRCT desmoplastic small round cell tumor, SFT solitary fibrous tumor, AS angiosarcoma, EHE epithelioid hemangioendothelioma, DDLPS dedifferentiated liposarcoma, MLPS myxoid liposarcoma, PleoLPS pleomorphic liposarcoma, ES epithelioid sarcoma, CS chondrosarcoma, ESMC extraskeletal myxoid chondrosarcoma, MC mesenchymal chondrosarcoma, ASPS alveolar soft part sarcoma
aApproximate