TABLE 3.
Clinical benefit qualifications and underlying evidence aspects
| Clinical benefit (score) | Trial design | Endpoint scored | Preliminary score a | Increased toxicity | Reduced toxicity a | Improved QoL | SMA indications (initial approval, N = 15) | Converted b CMA indications (initial approval, N = 15) | Converted b CMA indications (conversion c , N = 15) | Unconverted b CMA indications (initial approval, N = 17) |
|---|---|---|---|---|---|---|---|---|---|---|
| Substantial | 5 (33%) | 1 (7%) | 7 (47%) | 1 (6%) | ||||||
| 5/A | Controlled | OS | 4/4 | +1 | +1 | 1 | ||||
| Controlled | DFS | A | 1 | |||||||
| 4 | Controlled | OS | 4/4 | 1 | 1 | |||||
| Controlled | PFS/TTP | 3/3 | +1 | 2 | 4 | |||||
| Controlled | PFS/TTP | 3/3 | +1 | 1 | ||||||
| Controlled, non‐inferiority | OS | 4/4 | x d | x d | 1 | |||||
| Controlled, non‐inferiority | PFS/TTP | 4/4 | x d | 1 | ||||||
| Single arm | ORR | 3/3 | +1 | 1 | ||||||
| Moderate | 6 (40%) | 8 (53%) | 7 (47%) | 12 (71%) | ||||||
| 3 | Controlled | OS | 3/4 | 1 | ||||||
| Controlled | PFS/TTP | 3/3 | 3 | 3 | 4 | 2 | ||||
| Single arm | ORR | 3/3 | 2 | 5 | 3 | 10 | ||||
| Low | 4 (27%) | 6 (40%) | 1 (7%) | 4 (24%) | ||||||
| 2 | Controlled | OS | 2/4 | 1 | ||||||
| Controlled | PFS | 3/3 | −1 | 1 | ||||||
| Controlled | CRR | 2/2 | 1 | |||||||
| Single arm | ORR | 3/3 | −1 | 2 | ||||||
| Single arm | ORR | 2/3 | 1 | 5 | ||||||
| 1 | Controlled | PFS/TTP | 1/4 | 1 | 1 | |||||
| Controlled | OS | 1/4 | 1 | |||||||
| Single arm | ORR | 1/3 | 1 | |||||||
| Distribution of clinical benefit scores (median [IQR]) | 3.0 (2.5–4.0) | 3.0 (2.0–3.0) | 3.0 (3.0–4.0) | 3.0 (3.0–3.0) | ||||||
CMA, conditional marketing authorization; CRR, complete response rate; DFS, disease‐free survival; IQR, interquartile range; ORR, overall response rate; OS, overall survival; PFS, progression‐free survival; QoL, quality of life; SMA, standard marketing authorization; TTP, time to progression.
Grade 3/4, impacting daily well‐being.
(Un)converted as at 31 December 2020.
Including the gastrointestinal stromal cancer indication of sunitinib.
Preliminary score already includes improved QoL and/or reduced toxicity: this indicates the clinical benefit in the context of the non‐inferior efficacy outcome.
The ESMO‐MCBS preliminary clinical benefit score that is reflected by the available evidence on the scored endpoint. This score may be adjusted in case of increased toxicity, reduced toxicity and/or improved QoL.