Table 1: Study interventions.

RegimenDrugPlanned (mean) dose per treatment cycleaDuration of treatment (mean administrations)RouteClinical trialPFS and OS data in the model

Olara + DoxOlara15 (14.0) mg/kg on day 1 and day 821-day treatment cycles until disease progression (19.4 administrations)bIV infusion (60 minutes)Tap et al. [17]PFS: JGDG KM curve
OS: gamma function, mean parameters (SE)c
Intercept: 2.38 (0.34)
Scale: 1.08 (0.08)
Treatment—Dox: −0.66 (0.43)
LOT, first line: 0.56 (0.29)
Treatment × LOT: −0.34 (0.44)
Tumor—LMS: −0.29 (0.34)
Treatment × tumor: 0.40 (0.48)
Sex—male: −0.48 (0.21)
ECOG score of 0 : 0.91 (0.22)
Shape: −0.68 (0.40)
Dox75 (73.7) mg/m2 on day 1Up to eight 21-day treatment cycles or disease progression (5.7 administrations)IV push
Dex750 (707.0) mg/m2 on day 1Treatment cycles 5–8 (3.6 administrations for 59% of patients)IV infusion within 30 minutes prior to every Dox infusion
DoxDox75 (74.7) mg/m2 on day 1Up to eight 21-day treatment cycles or until disease progression (4.4 administrations)IV push (15–60 minutes)
Dex750 (725.8) mg/m2 on day 1Treatment cycles 5–8 (3.1 administrations for 45% of patients)IV infusion within 30 minutes prior to every Dox infusion

AIMIfo2.5 g/m2 on day 1, day 2, day 3, and day 4Up to six 21-day treatment cycles or until disease progression (4.4 cycles)dIV infusion (60 minutes)Judson et al. [12]HR (95% CrI)e
Olara + Dox versus AIM
PFS: 0.907 (0.573, 1.438)f
OS: 0.559 (0.343, 0.897)
NMA [23]
Dox25 mg/m2 on day 1, day 2, and day 3IV push
Mesna2 g/m2 on day 1, day 2, day 3, and day 4Each cycleIV infusion and IV push
G-CSF6 mg pegfilgrastim on day 5Each cycleSC
Dexi250 mg/m2,g on day 1, day 2, and day 3Treatment cycles 5 and 6IV infusion

GemDoc (GeDDiS)Gem675 mg/m2 on day 1 and day 8Up to six 21-day treatment cycles or until disease progression (4.1 cycles)hIV infusion (90 minutes)Seddon et al. [19]HR (95% CrI)e
Olara + Dox versus GemDoc
PFS: 0.522 (0.321, 0.862)f
OS: 0.432 (0.252, 0.744)
NMA [23]
Doc75 mg/m2 on day 8IV infusion (60 minutes)

GemDoc (Maki)Gem900 mg/m2 on day 1 and day 8Up to six or eight 21-day treatment cycles or until disease progression (4.0 cycles)jIV infusion (90 minutes)Maki et al. [21]Efficacy is assumed to be equivalent to Dox in the JGDG trial
Doc100 mg/m2 on day 8IV infusion (60 minutes)
G-CSF6 mg pegfilgrastim on day 9SC

PLDPLD50 mg/m2 on day 1Up to six 28-day treatment cycles or until disease progression (3.4 cycles)IV infusion (60 minutes)Judson et al. [22]Efficacy is assumed to be equivalent to Dox in the JGDG trialk

MAIDMesna2.5 g/m2 on day 1, day 2, and day 3Up to six 21-day treatment cycles or until disease progression (4.4 cycles)lIV infusion (60 minutes)Bui-Nguyen et al. [20]Efficacy is assumed to be equivalent to AIM
Dox20 mg/m2 on day 1, day 2, and day 3IV infusion (<60 minutes or IV push)
Ifom2.5 g/m2 on day 1, day 2, and day 3IV infusion (180 minutes)
DTIC300 mg/m2 on day 1, day 2, and day 3IV infusion (60 minutes)
Dexi200 mg/m2,g on day 1, day 2, and day 3Treatment cycles 5 and 6IV infusion

AIM = ifosfamide + doxorubicin + mesna; CrI = credible interval; Dex = dexrazoxane; Dox = doxorubicin; DTIC = dacarbazine; ECOG = Eastern Cooperative Oncology Group; G-CSF = granulocyte-colony stimulating factor; Gem = gemcitabine; GemDoc = gemcitabine + docetaxel; HR = hazard ratio; Ifo = ifosfamide; ITT = intention-to-treat; IV = intravenous; KM = Kaplan–Meier; LMS = leiomyosarcoma; LOT = line of treatment; MAID = mesna + doxorubicin + ifosfamide + dacarbazine; NMA = network meta-analysis; Olara = olaratumab; Olara+Dox = olaratumab + doxorubicin; OS = overall survival; PFS = progression-free survival; PLD = pegylated liposomal doxorubicin; SC = subcutaneous; SE = standard error. aMean dose was available only for Olara + Dox and Dox from the JGDG trial. For the other regimens, the planned dose was assumed. bIn the JGDG trial, all patients had discontinued their randomized treatment at the data cutoff point; therefore, there was no need for prediction of treatment costs beyond trial follow-up. cThe survival function for Olara + Dox assumed no treatment effect after 32 months (i.e., applied a HR of 1.00). Both functions were adjusted to account for increased risk of death from other causes. dEstimated from Judson et al. [24]. eEstimated using stratified ITT analysis HR for Olara + Dox versus Dox in the NMA. fEstimated using the investigator-assessed PFS HR for Olara + Dox versus Dox in the NMA. gTen times the Dox dose [15]. hAssumed to equal to that for Dox in the trial by Judson et al. [12]; estimated from Judson et al. [24]. iDex was not administered with AIM and MAID in the studies by Judson et al. [12] and Bui-Nguyen et al. [20], respectively. However, as Dex was administered to patients receiving Dox from cycles 5 to 8 in the JGDG trial, it was assumed that a proportion of patients receiving five and six cycles of AIM or MAID also received Dex. jBased on the median number of cycles reported by Maki et al. [21]. kJudson et al. [22] reported equivalent antitumor activity for Dox and PLD. lAssumed the same as AIM. mNormal saline (1000 mL) is administered for 2 hours after each Ifo dose. The associated administration cost was added to the Ifo administration cost; the cost of the normal saline product was assumed to be negligible.