Pembrolizumab plus axitinib and nivolumab plus ipilimumab as first-line treatments of advanced intermediate- or poor-risk renal-cell carcinoma: a number needed to treat analysis from the Brazilian private perspective

Figures & data

Table 1. General baseline characteristics of the patients included in both studies, KEYNOTE-426 and CHECKMATE-214.

	KEYNOTE-426^a		CHECKMATE-214^b
	Pembrolizumab + Axitinib (N = 432)	Sunitinib (N = 429)	Ipilimumab + Nivolumab (N = 425)	Sunitinib (N = 422)
Median age (range) – years	62 (30–89)	61 (26–90)	62 (26–85)	61 (21–85)
Male sex – no. (%)	308 (71.3)	320 (74.6)	314 (74)	301 (71)
IMDC prognostic risk – no. (%)
Favorable	138 (31.9)	131 (30.5)	–	–
Intermediate	238 (55.1)	246 (57.3)	334 (79)	333 (79)
Poor	56 (13.0)	52 (12.1)	91 (21)	89 (21)
Region of enrollment – no. (%)
North America	104 (24.1)	103 (24.0)	112 (26)	111 (26)
Western Europe	106 (24.5)	104 (24.2)	–	–
Canada and Europe	–	–	148 (35)	146 (35)
Rest of the world	222 (51.4)	222 (51.7)	165 (39)	165 (39)
PD-L1 combined positive score – no./total no. with data (%)
<1%	167/410 (40.7)	158/412 (38.3)	284/384 (74)	278/392 (71)
≥1%	243/410 (59.3)	254/412 (61.7)	100/384 (26)	114/392 (29)
No. of organs with metastases – no. (%)
1	114 (26.4)	96 (22.4)	90 (21)	84 (20)
≥2	315 (72.9)	331 (77.2)	335 (79)	337 (80)
Most common sites of metastasis – no. (%)
Lung	312 (72.2)	309 (72.0)	294 (69)	296 (70)
Lymph node	199 (46.1)	197 (45.9)	190 (45)	216 (51)
Bone	103 (23.8)	103 (24.0)	95 (22)	97 (23)
Adrenal gland	67 (15.5)	76 (17.7)	–	–
Liver	66 (15.3)	71 (16.6)	88 (21)	89 (21)
Previous radiotherapy — no. (%)	41 (9.5)	40 (9.3)	52 (12)	52 (12)
Previous nephrectomy — no. (%)	357 (82.6)	358 (83.4)	341 (80)	319 (76)

Abbreviation. IMDC, International Metastatic Renal Cell Carcinoma Database Consortium.

^a Although KEYNOTE-426 assessed all IMDC patients, our analysis only addressed outcomes for those classified as intermediate- or poor-risk.

^b Only patients classified as intermediate- or poor-risk are reported.

Table 2. The 12-month OS and PFS rates^a from KEYNOTE-426^b and CHECKMATE-214^b for intermediate- or poor-risk patients.

	KEYNOTE-426		CHECKMATE-214
	Pembrolizumab + Axitinib	Sunitinib	Ipilimumab + Nivolumab	Sunitinib
OS (%)
Survival	87	71	80	72
Death	13	29	20	28
PFS (%)
Survival	56	40	41	36
Progression	44	60	59	64

Abbreviation. 95%CI, 95% confidence interval; OS, overall survival; PFS, progression-free survival.

^a Rounded proportions were used since only rounded values were presented as part of the CHECKMATE-214 publication.

^b Only patients classified as intermediate- or poor-risk are reported.

Table 3. Therapeutic regimen characteristics.

Commercial name	Keytruda	Inlyta	Opdivo	Opdivo	Yervoy
Drug	Pembrolizumab	Axitinib	Nivolumab	Nivolumab^a	Ipilimumab
Dosage	200 mg Q3W	5 mg twice a day	480 mg Q4W	3 mg/kg Q3W x4	1 mg/kg Q3W x 4
Presentation	100 mg/4 mL (25 mg/mL) solution in a single dose via.	5 mg tablets.	40 mg/4 mL, 100 mg/10 mL solution in a single dose vial.	240 mg/24 mL solution in a single dose vial.	50 mg/10 mL (5 mg/mL) in a single-use vial.

Abbreviations. Q3W, every three weeks; Q4W, every four weeks.

^a Induction phase with ipilimumab for 4 cycles.

Table 4. Cost calculation parameters.

Commercial name	Keytruda	Inlyta	Opdivo	Opdivo	Yervoy
Ex-factory price (BRL)	15,135.19	19,494.96	8,408.43	3,363.38	17,758.28
Cost per cycle (BRL)	30,270.38	649.83	40,360.48	20,180.24	35,516.56
Cycles at mean treatment time	13	266	6	4	4
Drug costs considering mean PFS (BRL)	393,515.00	172,854.78	242,163.00	80,721.00	142,066.00
Annual cost	524,585.69	236,538.12	403,604.80	80,720.96	142,066.24

Abbreviations. BRL, Brazilian Real; PFS, progression-free survival.

Table 5. Number needed to treat and cost of preventing an event for 12-month OS and PFS rate from KEYNOTE-426^a and CHECKMATE-214^a.

	Pembrolizumab + Axitinib	Nivolumab + Ipilimumab	Difference
OS
NNT^b (95%CI)	6 (5.27–7.66)	13 (10.18–16.20)	–
Cost per treatment (BRL)	623,025	508,637	–
COPE in BRL^c (95%CI)	3,893,903 (3,283,339 – 4,772,368)	6,357,965 (5,177,924–8,239,919)	−2,464,062
PFS
NNT^b (95%CI)	6 (5.27–7.66)	20 (15.46–28.31)	–
Cost per treatment (BRL)	623,025	508,637	–
COPE in BRL^c (95%CI)	3,893,903 (3,283,339 – 4,772,368)	10,172,744 (7,863,528–14,399,513)	−6,278,841

Abbreviations. 95%CI, 95% confidence interval; BRL, Brazilian Real; COPE, cost of preventing an event; NNT, number needed to treat; OS, overall survival; PFS, progression-free survival.

^a Only patients classified as intermediate- or poor-risk are reported.

^b NNT values are shown as rounded numbers, since it is not possible to treat less than one patient.

^c COPE was calculated considering not rounded NNT (6.25 and 12.5 for OS and 6.25 and 20.0 for PFS).