Validation of overall survival extrapolations made by TLV in the assessment of cost-effectiveness of oncology drugs in Sweden – A pilot study comparing extrapolated and observed life-years gained

Figures & data

Figure 1. PRISMA diagram for the inclusion of relevant TLV appraisals.

Table 1. Characteristics of identified TLV appraisals.

Drug brand name (Comparator): Appraisal no; Appraisal for PBB/Regions	Indication	Clinical trial^10^–^21/ Number of patients/NCT identifier	Follow-up time in months in original vs follow-up trial	Parametric model for OS in TLV base case	TLV and company base case is the same (life-years gained)	External data used for OS extrapolation in TLV base case**	Existence of cross-over
Cabometyx (Everolimus): 3734/2016; PBB	Advanced renal cell carcinoma	METEOR/n = 658/NCT01865747	30 vs. 38	Log-logistic	Yes	No	No
Gazyvaro (Chlorambucil): 2240/2013; Regions	Chronic lymphocytic leukemia	CLL11/ n = 356/NCT01010061	37 vs. 87	Markov model*	Yes	Yes	Yes, in original study (8%). Unknown in follow-up
Kadcyla (Lapatinib + capecitabine): 1310/2013; Regions	HER2-positive breast cancer	EMILIA/n = 951/NCT00829166	27 vs. 68	Gamma	No. Different comparator in company base case	No	Unknown in original study. Yes, in follow-up (27%).
Keytruda (Docetaxel): 1166/2016; Regions	Non-small cell lung cancer	Keynote-010/n = 1034/NCT01905657	23 vs. 52	Exponential	Yes	No	Unknown in original and follow-up study
Keytruda (Platinum-based chemotherapy): 3331/2016; Regions	Non-small cell lung cancer	Keynote-024/n = 305/NCT02142738	18 vs. 32	Log-logistic	No. Company base case was exponential distribution.	No	Yes, in original study and follow-up (43.7%).
Kyprolis + dexamethasone (Bortezomib + dexamethasone): 2018/2016; Regions	Multiple myeloma	Endeavor/n = 929/NCT01568866	41 vs. 47	Weibull	N/A	Yes	Unknown in original and follow-up study
Mekinist + dabrafenib (Dabrafenib + placebo): 3948/2015; PBB	Malignant melanoma	COMBI-D/ n = 423/NCT01072175	32 vs. 76	Log-normal	Yes	No	Unknown in original study. Yes, in follow-up (12%).
Opdivo (Methotrexate, docetaxel or cetuximab): 2964/2016; Regions	Head and neck cancer	Checkmate-141/n = 361/NCT02105636	24 vs. 37	Active: Log-normal Control: Log-logistic	Yes	No	Yes, in original study. Unknown in follow-up
Opdivo (Docetaxel): 875/2016; Regions	Non-small cell lung cancer	Checkmate-057/n = 582/NCT01673867	25 vs. 36	Active: Log-normal Control: Generalized gamma	No	No	Unknown in original study. Yes, in follow-up

*For Gazyvaro OS has been estimated from parametric extrapolation of progression-free survival (PFS) and post-progression survival (PPS). PFS treatment: Weibull; PFS control: Log-logistic; PPS: Exponential.

**Due to limited follow-up and/or immature data at the time of TLV’s decision, additional clinical trials or registry data have been used to estimate long-term OS (for Gazyvaro and Kyprolis). For Kyprolis the study by⁵ was used to estimate OS in the control group. For Gazyvaro the study by⁶ was used to estimate post-progression survival.

Figure 2. Observed, modelled, and extrapolated overall survival (OS).

Table 2. Months (area under the curve) in the follow-up period for the treatment-, and control group, and for the difference between the treatment groups, for identified drugs (TLV-appraisals), comparing model extrapolation with observed data. Model over/under estimation is expressed in %.

Drug brand	Follow-up data		Extrapolation/model		Model over/under estimation
name: Appraisal no	Treatment	Control	Treatment	Control	Difference	Treatment	Control
Cabometyx: 3734/2016	2.01	0.97	1.89	1.36	−48.26	−5.53	40.08
Gazyvaro: 2240/2013	23.58	19.11	20.06	14.01	35.60	−14.90	−26.70
Kadcyla: 1310/2013	14.24	9.52	13.29	8.20	7.74	−6.67	−13.81
Keytruda: 1166/2016	5.35	3.14	6.06	1.47	107.59	13.27	−53.26
Keytruda: 3331/2016	6.98	4.86	7.00	4.83	2.86	0.39	−0.69
Kyprolis: 2018/2016	1.94	1.41	1.93	1.56	−30.88	−0.62	10.79
Mekinist: 3948/2015	15.44	13.09	11.05	8.49	8.78	−28.42	−35.10
Opdivo: 2964/2016	1.68	0.50	1.60	0.56	−12.10	−4.83	12.48
Opdivo: 875/2016	1.69	1.14	2.08	0.74	143.46	23.13	−35.24
Average	8.10	5.97	7.22	4.58	23.87	−2.69	−11.27

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