Cost-Effectiveness of Olaratumab in Combination with Doxorubicin for Patients with Soft Tissue Sarcoma in the United States

Table 1

Study interventions.

Regimen	Drug	Planned (mean) dose per treatment cycle^a	Duration of treatment (mean administrations)	Route	Clinical trial	PFS and OS data in the model
Olara + Dox	Olara	15 (14.0) mg/kg on day 1 and day 8	21-day treatment cycles until disease progression (19.4 administrations)^b	IV 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)
	Dox	75 (73.7) mg/m^2 on day 1	Up to eight 21-day treatment cycles or disease progression (5.7 administrations)	IV push
	Dex	750 (707.0) mg/m^2 on day 1	Treatment cycles 5–8 (3.6 administrations for 59% of patients)	IV infusion within 30 minutes prior to every Dox infusion
Dox	Dox	75 (74.7) mg/m^2 on day 1	Up to eight 21-day treatment cycles or until disease progression (4.4 administrations)	IV push (15–60 minutes)
	Dex	750 (725.8) mg/m^2 on day 1	Treatment cycles 5–8 (3.1 administrations for 45% of patients)	IV infusion within 30 minutes prior to every Dox infusion
AIM	Ifo	2.5 g/m^2 on day 1, day 2, day 3, and day 4	Up to six 21-day treatment cycles or until disease progression (4.4 cycles)^d	IV 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]
	Dox	25 mg/m^2 on day 1, day 2, and day 3		IV push
	Mesna	2 g/m^2 on day 1, day 2, day 3, and day 4	Each cycle	IV infusion and IV push
	G-CSF	6 mg pegfilgrastim on day 5	Each cycle	SC
	Dex^i	250 mg/m^2,^g on day 1, day 2, and day 3	Treatment cycles 5 and 6	IV infusion
GemDoc (GeDDiS)	Gem	675 mg/m^2 on day 1 and day 8	Up to six 21-day treatment cycles or until disease progression (4.1 cycles)^h	IV 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]
	Doc	75 mg/m^2 on day 8		IV infusion (60 minutes)
GemDoc (Maki)	Gem	900 mg/m^2 on day 1 and day 8	Up to six or eight 21-day treatment cycles or until disease progression (4.0 cycles)^j	IV infusion (90 minutes)	Maki et al. [21]	Efficacy is assumed to be equivalent to Dox in the JGDG trial
	Doc	100 mg/m^2 on day 8		IV infusion (60 minutes)
	G-CSF	6 mg pegfilgrastim on day 9		SC
PLD	PLD	50 mg/m^2 on day 1	Up 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 trial^k
MAID	Mesna	2.5 g/m^2 on day 1, day 2, and day 3	Up to six 21-day treatment cycles or until disease progression (4.4 cycles)^l	IV infusion (60 minutes)	Bui-Nguyen et al. [20]	Efficacy is assumed to be equivalent to AIM
	Dox	20 mg/m^2 on day 1, day 2, and day 3		IV infusion (<60 minutes or IV push)
	Ifo^m	2.5 g/m^2 on day 1, day 2, and day 3		IV infusion (180 minutes)
	DTIC	300 mg/m^2 on day 1, day 2, and day 3		IV infusion (60 minutes)
	Dex^i	200 mg/m^2,^g on day 1, day 2, and day 3	Treatment cycles 5 and 6	IV 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.