ET743-SAR-3007: trial | Bending the Curve: Trial by Trial

ET743-SAR-3007

Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial

Phase 3N = 518NCT01343277

Population

518 randomised patients with advanced liposarcoma or leiomyosarcoma previously treated with an anthracycline and at least one additional systemic regimen

Design

Randomised 2:1 phase 3 trial of trabectedin versus dacarbazine, each given intravenously every 3 weeks, in patients with advanced liposarcoma or leiomyosarcoma after an anthracycline and at least one additional systemic regimen. Primary-report arm sizes shown; the final overall survival report counts 577 randomised patients (384 trabectedin, 193 dacarbazine).

Primary endpoint

Arms

Dacarbazine (control, n = 173): Dacarbazine intravenously every 3 weeks
Trabectedin (experimental, n = 345): Trabectedin intravenously every 3 weeks

People

Demetri GD

OSHR 0.87Δ median OS−0.5 monthsPFSHR 0.55Δ median PFS+2.7 monthsOSHR 0.93 (95% CI 0.75–1.15)Δ median OS+0.6 months

Show the numbers

Results reported for ET743-SAR-3007
Endpoint	Analysis	Trabectedin	Dacarbazine	Effect
OSRandomised patients at the interim overall survival analysis (64% censored)	interimDemetri 2016	median 12.4 months	median 12.9 months	HR 0.87P=.37The abstract calls this the primary endpoint and describes the interim analysis as showing a 13% reduction in the risk of death; no confidence interval is printed.
PFSRandomised patients; analysis population not stated in the abstract	finalDemetri 2016	median 4.2 months	median 1.5 months	HR 0.55P<.001A secondary endpoint; no confidence interval is printed in the abstract.
OS577 randomised patients at the final overall survival analysis	finalmedian follow-up 21.2 monthsPatel 2019	median 13.7 months (12.2–16.0)	median 13.1 months (9.1–16.2)	HR 0.93 (95% CI 0.75–1.15)P=.49Later report of the same trial; unstratified final OS analysis (clinical cutoff 5 January 2015; 381 deaths). The authors report post-study anticancer therapy in most patients in both arms (71% vs 69%) and their sensitivity analyses suggest confounding of OS.

Results reported for ET743-SAR-3007
Endpoint	Analysis	Trabectedin	Dacarbazine	Effect
OSRandomised patients at the interim overall survival analysis (64% censored)	interimDemetri 2016	median 12.4 months	median 12.9 months	HR 0.87P=.37The abstract calls this the primary endpoint and describes the interim analysis as showing a 13% reduction in the risk of death; no confidence interval is printed.
PFSRandomised patients; analysis population not stated in the abstract	finalDemetri 2016	median 4.2 months	median 1.5 months	HR 0.55P<.001A secondary endpoint; no confidence interval is printed in the abstract.
OS577 randomised patients at the final overall survival analysis	finalmedian follow-up 21.2 monthsPatel 2019	median 13.7 months (12.2–16.0)	median 13.1 months (9.1–16.2)	HR 0.93 (95% CI 0.75–1.15)P=.49Later report of the same trial; unstratified final OS analysis (clinical cutoff 5 January 2015; 381 deaths). The authors report post-study anticancer therapy in most patients in both arms (71% vs 69%) and their sensitivity analyses suggest confounding of OS.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
OS	0.93	0.75–1.15

Illustrative — modelled from reported values, not trial data. OS, interim.

Show curves

Trabectedin (experimental)
Dacarbazine (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Trabectedin	Dacarbazine
0	100.0%	100.0%
8	63.9%	65.1%
16	40.9%	42.3%
24	26.1%	27.5%
32	16.7%	17.9%

Illustrative — modelled from reported values, not trial data. PFS, final.

Show curves

Trabectedin (experimental)
Dacarbazine (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Trabectedin	Dacarbazine
0	100.0%	100.0%
3	61.0%	25.0%
5	43.8%	9.9%
8	26.7%	2.5%
11	16.3%	0.6%

Appears in

2015 Trabectedin vs dacarbazine in liposarcoma and leiomyosarcoma

Sources

Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, et al. Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. J Clin Oncol. 2016;34(8):786-93.
PubMed DOI
Patel S, von Mehren M, Reed DR, Kaiser P, Charlson J, Ryan CW, et al. Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Cancer. 2019;125(15):2610-2620.
PubMed DOI