Maintenance therapy and drug holiday in sarcoma patients: systematic review

Figures & data

Table 1. Trials assessing maintenance therapy with immune-stimulating agents in patients with localized osteosarcoma.

Study	Bielack et al. [3]		Meyers et al. [5]
Maintenance therapy	Switch		Continuation
	IFNα-2b –	IFNα-2b +	MTP–	MTP+
n	359	357	172 + 167	168 + 170
3-year EFS	74%	77%	–	–
6-year EFS			61%	67%
Hazard ratio (95% CI), p	0.83		0.80
	(0.61–1.12), p = .214		(0.62–1.0), p = .08
5-year OS	81%	84%	–	–
6-year OS	–	–	70%	78%
Hazard ratio (95% CI), p	0.77		0.71
	(0.50–1.19), p = not done		(0.52–0.96), p = .03

n: number of patients; EFS: event-free survival; OS: overall survival; 95% CI: 95% confidence interval, p = p-value.

Table 2. Switch maintenance therapy with cyclophosphamide and vinorelbine for localized high-risk rhabdomyosarcoma.

	Observation arm	Switch maintenance therapy arm
n	186	185
5-year DFS (ITT)	70%	78%
Hazard ratio		0.68
(95% CI), p		(0.45–1.02), p = .061
5-year OS (ITT)	74%	87%
Hazard ratio		0.52
(95% CI), p		(0.32–0.86), p = .0097
5-year DFS (PP)	70%	78%
Hazard ratio		0.67
(95% CI), p		(0.44–1.01), p = .053
5-year OS (PP)	74%	86%
Hazard ratio		0.53
(95% CI), p		(0.32–0.87), p = 0.011

n: number of patients, DFS: disease-free survival, OS: overall survival, ITT: intention-to-treat analysis; PP: per protocol analysis; 95% CI: 95% confidence interval, p = p-value.

Table 3. High-dose chemotherapy versus metronomic chemotherapy after first-line chemotherapy in children with metastatic soft-tissue sarcoma.

	High-dose chemotherapy	Switch maintenance therapy	p
Total (n = 96)	n = 45	n = 51	–
5-year OS	27%	52%	.03
RMS patients, only (n = 74)	n = 34	n = 40	–
5-year OS	15%	52%	.001
Patients without bone or bone marrow involvement, only (n = 51)	n = 20	n = 31	–
5-year OS	40%	73%	.04

n: number of patients; OS: overall survival; p: p-value.

Table 4. Clinical trials assessing continuation maintenance therapy with bevacizumab in advanced soft-tissue sarcoma patients.

	Ray-Coquard et al. [14]		Chilsom et al. [15]
Sarcomas	Advanced angiosarcoma		Advanced soft-tissue sarcoma
Standard arm	Weekly paclitaxel (6 cycles)		IVADo (4 cycles) then
			IVA (5 cycles) then
			Maintenance chemotherapy
	Bevacizumab –	Bevacizumab +	Bevacizumab –	Bevacizumab +
n	24	25	80	74
ORR	46%	28%	36%	54%
median PFS (months)	6.6	6.6	–	–
median EFS (months)	–	–	14.9	20.6
median OS (months)	19.5	15.9	–	–
Patients experiencing grade 3/4 toxicity	22%	44%	90%	94%

n: number of patients, ORR: best objective response rate; PFS: progression-free survival; EFS: event-free survival; OS: overall survival; IVADo: ifosfamide/vincristine/actinomycin/doxorubicin; IVA: ifosfamide/vincristine/actinomycin.

Table 5. Ridaforolimus as switch maintenance therapy in sarcoma patients showing non-progressive disease after the first-, second-, or third-line chemotherapy.

	Placebo	Ridaforolimus
n	364	347
Non-progressive disease at 4 months	29%	41%
p		p < .001
median PFS (1), months	14.6	17.7
Hazard ratio		0.72
(95% CI), p		(0.61–0.85), p < .001
median PFS (2), months	14.7	22.4
Hazard ratio		0.69
(95% CI), p		(0.58–0.81), p < .001
Median OS, months	85.3	90.6
Hazard ratio		0.93
(95% CI), p		(0.78–1.12), p = .456

n: number of patients, PFS: progression-free survival, OS: overall survival; 95% CI: 95% confidence interval, p = p-value, (1) PFS according to the central blinded review, (2) PFS according to investigator assessment.

Table 6. Trabectedin continuation versus drug holiday and rechallenge of in soft-tissue sarcoma patients showing controlled disease after six cycles of trabectedin.

	Continuation	Drug holiday
n	27	26
ORR	15%	11%
Median PFS, months	5.3	3.5
6-month PFS	48%	19%
Median OS, months	27.0	17.1
18-month OS	70%	44%
Q-TWIST, months	16.8	13.5

ORR: objective response rate; PFS: progression-free survival; OS: overall survival; Q-TWIST: quality-adjusted time without symptom and tumor progression.

Bielack SS, Smeland S, Whelan JS, et al. Methotrexate, doxorubicin, and cisplatin (MAP) plus maintenance pegylated interferon alfa-2b versus MAP alone in patients with resectable high-grade osteosarcoma and good histologic response to preoperative MAP: first results of the EURAMOS-1 good response randomized controlled trial. JCO. 2015;33(20):2279–2287.

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Chisholm JC, Merks JHM, Casanova M, et al. Open-label, multicentre, randomised, phase II study of the EpSSG and the ITCC evaluating the addition of bevacizumab to chemotherapy in childhood and adolescent patients with metastatic soft tissue sarcoma (the BERNIE study). Eur J Cancer. 2017;83:177–184.

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