End points of clinical trials in metastatic castration-resistant prostate cancer: A systematic review

Table 2 Characteristics of randomized clinical trials including overall survival as the primary end point after first-line and/or second-line medical treatment of metastatic castration-resistant prostate cancer

Trial	Arms	No. pts	Publication year	Main conclusion	Median OS
LSG Trial[18]	LIA	160	1998	After adjustment for baseline prognostic factors, HR for OS favored the first arm	10.3 mo
	CPA	161			10.3 mo
CALGB 9182[19]	MXN + HDC	119	1999	Better PSA-RR and PFS in the first arm	12.3 mo
	HDC	123			12.6 mo
HOG/FNC Trial[20]	VBL + ESM	95	1999	Better PSA-RR and PFS in the first arm	11.9 mo
	VBL	98			9.2 mo
SWOG 9916[6]	DOC + ESM	338	2004	Longer OS in the first arm	17.51 mo
	MXN + PDN	336			15.6 mo
TAX327[5]	MXN + PDN	337	2004	DOC-based chemotherapy is the new standard first-line treatment of mCRPC	16.5 mo
	DOC + PDN	335			18.91 mo
	wDOC + PDN	334			17.4 mo
3SPARC[21]	SPT + PDN	635	2009	Better PSA-RR in the first arm	61.3 wk
	Placebo + PDN	315			61.4 wk
2TROPIC[7]	CBZ + PDN	378	2010	CBZ-based therapy is effective in mCRPC progressing to DOC	15.11 mo
	MXN + PDN	377			12.7 mo
IMPACT[22]	SIP-T	341	2010	Similar results	25.81 mo
	Placebo	171			21.7 mo
2COU-AA-301[8]	ABI + PDN	797	2011	ABI hormonal therapy is effective in mCRPC progressing to DOC	14.81 mo
	Placebo + PDN	398			10.9 mo
ASCENT-2[23]	DOC + DN101	477	2011	DN101 is inferior to PDN	17.8 mo
	DOC + PDN	476			20.21 mo
CALGB 90401[24]	DOC + PDN + BEV	524	2012	Better PSA-RR and PFS in the first arm	22.6 mo
	DOC + PDN + Placeb	526			21.5 mo
2AFFIRM[9]	ENZ	800	2012	ENZ hormonal therapy is effective in mCRPC progressing to DOC	18.41 mo
	Placebo	399			13.6 mo
ENTHUSE M1C[25]	DOC + ZBT	524	2013	Similar results	20.0 mo
	DOC + Placebo	528			19.2 mo
3ALSYMPCA[10]	Radium-223	614	2013	Radium-223 effective in mCRPC with painful bone metastases	14.91 mo
	Placebo	307			11.3 mo

¹Statistically significant difference;

²Trial of second-line medical treatment;

³Trial of first or second-line medical treatment. ABI: Abiraterone; BEV: Bevacizumab; CBZ: Cabazitaxel; CPA: Cyproterone acetate; DN101: High-dose calcitriol; DOC: Docetaxel; ENZ: Enzalutamide; ESM: Estramustine; HDC: Hydrocortisone; HR: Hazard ratio; LIA: Liarozole; mCRPC: Metastatic castration-resistant prostate cancer; MXN: Mitoxantrone; OS: Overall survival; PDN: Prednisone; PFS: Progression-free survival; PSA-RR: Prostate-specific antigen response rate; SIP-T: Sipuleucel-T; SPT: Satraplatin; VBL: Vinblastine; wDOC: Weekly-docetaxel; ZBT: Zibotentan.