Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial: trial

Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial

Population

148 patients (15 in phase 1b; 133 randomised in phase 2) with locally advanced or metastatic soft-tissue sarcoma not previously treated with an anthracycline

Design

Open-label phase 1b (15 patients treated with olaratumab plus doxorubicin) and randomised phase 2 (1:1, minimisation) at 16 US sites; anthracycline-naive patients with advanced or metastatic soft-tissue sarcoma, ECOG performance status 0 to 2 and tissue available for PDGFR-alpha testing. Up to eight 21-day cycles. Phase 2 primary endpoint PFS with two-sided alpha 0.2 and power 0.8.

Primary endpoint

PFS

Arms

Doxorubicin (control, n = 67): Doxorubicin 75 mg/m2 on day 1 of each 21-day cycle, up to eight cycles
Olaratumab plus doxorubicin (experimental, n = 66): Olaratumab 15 mg/kg on days 1 and 8 plus doxorubicin 75 mg/m2 on day 1 of each 21-day cycle, up to eight cycles

People

Tap WD

PFSHR 0.67 (95% CI 0.44–1.02)Δ median PFS+2.5 monthsOSHR 0.46 (95% CI 0.30–0.71)Δ median OS+11.8 monthsΔ ORR+6.3 points

Show the numbers

Results reported for Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial
Endpoint	Analysis	Olaratumab plus doxorubicin	Doxorubicin	Effect
PFSPhase 2 randomised patients (133)	primaryTap 2016	median 6.6 months (4.1–8.3)	median 4.1 months (2.8–5.4)	HR 0.67 (95% CI 0.44–1.02)P=0.0615Stratified HR. The abstract states the study met its predefined primary endpoint using a two-sided alpha of 0.2.
OSPhase 2 randomised patients (133)	primaryTap 2016	median 26.5 months (20.9–31.7)	median 14.7 months (9.2–17.1)	HR 0.46 (95% CI 0.30–0.71)P=0.0003Stratified HR. Overall survival was not the phase 2 primary endpoint.
ORRPhase 2 randomised patients (133)	primaryTap 2016	18.2% (9.8–29.6%)	11.9% (5.3–22.2%)	P=0.3421

Results reported for Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial
Endpoint	Analysis	Olaratumab plus doxorubicin	Doxorubicin	Effect
PFSPhase 2 randomised patients (133)	primaryTap 2016	median 6.6 months (4.1–8.3)	median 4.1 months (2.8–5.4)	HR 0.67 (95% CI 0.44–1.02)P=0.0615Stratified HR. The abstract states the study met its predefined primary endpoint using a two-sided alpha of 0.2.
OSPhase 2 randomised patients (133)	primaryTap 2016	median 26.5 months (20.9–31.7)	median 14.7 months (9.2–17.1)	HR 0.46 (95% CI 0.30–0.71)P=0.0003Stratified HR. Overall survival was not the phase 2 primary endpoint.
ORRPhase 2 randomised patients (133)	primaryTap 2016	18.2% (9.8–29.6%)	11.9% (5.3–22.2%)	P=0.3421

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

Data table

Endpoint	HR	95% CI
PFS	0.67	0.44–1.02
OS	0.46	0.3–0.71

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

Show curves

Olaratumab plus doxorubicin (experimental)
Doxorubicin (control)

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

Data table (modelled values)

Months	Olaratumab plus doxorubicin	Doxorubicin
0	100.0%	100.0%
4	65.7%	50.9%
8	43.2%	25.9%
12	28.4%	13.2%
17	16.8%	5.6%

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

Show curves

Olaratumab plus doxorubicin (experimental)
Doxorubicin (control)

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

Data table (modelled values)

Months	Olaratumab plus doxorubicin	Doxorubicin
0	100.0%	100.0%
17	64.1%	44.9%
33	42.2%	21.1%
50	27.0%	9.5%
66	17.8%	4.5%

Appears in

2019 Olaratumab: phase 2 survival benefit not confirmed in ANNOUNCE

Sources

Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016;388(10043):488-97.
PubMed DOI